Rockville, March 27, 2023 (GLOBE NEWSWIRE) -- The market for MRI-guided radiation therapy systems is currently valued at US$ 545.1 million and is anticipated to generate US$ 2.89 billion in sales by the end of 2033. According to Fact.MR study, sales of MRI-guided radiation therapy systems will significantly increase at a 18.1% CAGR over the next 10 years.

Since MRI-guided radiation therapy systems are widely used in the treatment of cancer, the rising incidence of various malignancies is anticipated to significantly boost market growth over the course of the forecast period. It is also projected that rising capital spending on establishing healthcare infrastructure in developing economies would increase shipments of MRI-guided radiation therapy equipment in the future.

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Drivers

Restraints

Trends

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Regional Landscape:United States is expected to account for a substantial share in the market. Various factors such as developed healthcare infrastructure and the significant presence of reimbursement policies in the United States are expected to boost the adoption of MRI-guided radiation therapy systems.

Competitive LandscapeMRI-guided Radiation therapy systems market is highly consolidated. Companies such as Elekta AB and ViewRay are dominating the global market and currently, account for around 80% of the global market share.

In addition to this, companies are receiving FDA approvals to expand their sales potential across various countries.

Key Companies Profiled

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Key Questions Covered in the MRI-guided Radiation Therapy Systems Market Report

Check out more related studies published by Fact.MR Research:Hormone Replacement Therapy Market Size: The global hormone replacement therapy market size is estimated at USD 18.4 Billion in 2022 and is forecast to surpass USD 32.8 Billion by 2032, growing at a CAGR of 5.9% from 2022 to 2032.

Dual Therapy Stent Market Sales: The global duel therapy stent market sales valued at USD 11.09 Billion in 2022. The market is estimated to surpass a valuation of USD 23.07 Billion by 2032. The forecast duration of this report is 2022- 2032.

Rheumatoid Arthritis Stem Cell Therapy Market Share: The global rheumatoid arthritis stem cell therapy market share account for a share of USD 23.42 Billion in 2022. The market is anticipated to surpass the valuation of USD 33.30 Billion by end of the forecast period i.e. 2032. The rheumatoid arthritis stem cell market is expected to grow with a CAGR of 4.5 %.

Dual Antiplatelet Therapy Market Growth: Emergence of more effective oral and other anticoagulants may also hamper the market growth. In addition, high cost associated with the therapy and lack of its awareness in various regions across the globe will possibly confine the dual antiplatelet therapy market growth.

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MRI-guided Radiation Therapy Systems Revenue to Top US$2.89 ... - GlobeNewswire

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Axicabtagene ciloleucel (axi-cel; Yescarta) produced a statistically significant improvement in overall survival (OS) compared with standard-of-care (SOC) therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL) within 12 months of completion of first-line therapy, according to data from the primary OS analysis of the phase 3 ZUMA-7 trial (NCT03391466).1

Investigators plan to present full results from the OS analysis at an upcoming medical meeting.

Prior data from ZUMA-7 supported the FDA approval of axi-cel for the treatment of adult patients with LBCL that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy in April 2022.2

Findings for the primary end point of event-free survival (EFS) showed that at a median follow-up of 24.9 months, axi-cel generated an estimated median EFS of 8.3 months (95% CI, 4.5-15.8) compared with 2.0 months (95% CI, 1.6-2.8) with SOC treatment (HR, 0.40; 95% CI, 0.31-0.51; P <.0001). The estimated 18-month EFS rates in the experimental and control arms were 41.5% (95% CI, 34.2%-48.6%) and 17.0% (95% CI, 11.8%-23.0%), respectively.

Additionally, axi-cel elicited an objective response rate (ORR) of 83% (95% CI, 77%-88%) vs 50% (95% CI, 43%-58%) for SOC.

The randomized, open-label, global, multicenter, phase 3 ZUMA-7 study enrolled 359 patients with relapsed/refractory LBCL within 12 months of first-line therapy.3 First-line treatment needed to consist of an anti-CD20 monoclonal antibody, unless the investigator determined that tumor was CD20 negative, and an anthracycline-containing chemotherapy regimen.

Patients were excluded from the trial if they had a history of malignancy other than non-melanoma skin cancer or carcinoma in situ unless they were disease free for at least 3 years; received more than 1 line of therapy for LBCL; or had a history of autologous or allogeneic stem cell transplant.

Patients were randomly assigned 1:1 to a single infusion of axi-cel or SOC treatment with platinum-containing salvage chemotherapy followed by high-dose therapy and autologous stem cell transplant in responders.

Along with the primary end point of EFS, OS was designated as a clinically important prespecified key secondary endpoint. Other secondary end points included ORR, patient-reported outcomes, and safety.1

Regarding safety, findings from ZUMA-7 showed that axi-cel displayed a safety profile consistent with previous studies. Among the 168 patients evaluable for safety who received axi-cel, grade 3 or higher cytokine release syndrome (CRS) was reported in 7% of patients, and neurologic events occurred in 25% of patients. In the SOC arm, 83% of patients had high-grade adverse effects, mostly consisting of cytopenias.

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Second-line Axi-cel Elicits OS Benefit in Relapsed/Refractory LBCL - OncLive

Amrita Krishnan, MD (Moderator)

Director of the Judy and Bernard Briskin Center for Multiple Myeloma Research

City of Hope

Duarte, CA

CASE SUMMARY

A 60-year-old White woman was diagnosed with stage II multiple myeloma. She has a history of being a heavy smoker, with a gain (1q21) of cytogenetics and an ECOG performance score of 0. At the time, she was treated with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) induction therapy, followed by autologous stem cell transplantation. She achieved a complete remission with VRd and transplant and was minimal residual disease negative, then placed on lenalidomide maintenance therapy.

At a follow-up after 2 years on lenalidomide maintenance, the patient reported having severe fatigue and pain in her back and legs, which was disrupting her ability to continue working full time. A PET scan shows vertebral fracture at L1, lesions in both femurs, and an ECOG performance score of 1. Her current lab levels are now the following:

KRISHNAN: We have [a case here] with a biochemical and clinical progression.

Some of the [factors] to talk about are [whether] they are early vs late relapse, and [whether] that influences your decisions in terms of therapy?

CHHABRA: I tend to think patients who receive lenalidomide [Revlimid] maintenance, if they progress less than 36 months, [are considered an] early relapse patient. If they did not receive maintenance, then 18 months [is when I would consider them an early relapse patient]. Thats been my rule of thumb.

Although Ive also heard that 24 months is a good cutoff between early and late relapse. My preferred second-line regimen is not influenced by early vs late relapse, because Ive been using daratumumab [Darzalex]-based therapy, typically in combination with carfilzomib [Kyprolis] and dexamethasone [DKd]. If I have a clinical trial that is specifically for patients in the high-risk category, early relapse [is considered] less than 18 monthssuch as the allogeneic transplant trial, [with patients who] had less than 18 months from transplant.

KRISHNAN: Lets see [whether] every-one else agrees with you in terms of [the following]: (1) early relapse and (2) it sounds like youre a big DKd fan. Dr Lashkari, are you on the DKd bandwagon for first relapse?

LASHKARI: I would certainly recognize this as being a more aggressive relapse in a patient. I think youre right, [that] if this patient were treated initially, we would consider giving a daratumumab-based induction therapy, but she did very well, which is interesting. She had a complete response, and one can argue that if someone became [minimal residual disease] negative, it almost doesnt matter how you get there if you get there, because that in and of itself tends to portend a good prognosis. Considering someone relapsing within a couple years; invariably, this patient relapsed within 2 years because we see an M spike of 1.98 g.

Biochemical progression would have been defined as having greater than 0.5 g/dL, and that may have developed within a year from time of transplant. I would consider this patient to be an early relapse with aggressive clinical features, but I would certainly rebiopsy them to see what other clones are present.

In terms of treatment options, its interesting to get the information to come back. I dont know [whether] we can guide based on the information that comes back necessarily, unless perhaps they had an 11;14 translocation, in which case you can consider a venetoclax [Venclexta]-based treatment. I probably wouldnt even consider that for such a patient if they havent received a CD38 antibody. DKd is reasonable, and another option would be to go to daratumumab, pomalidomide [Pomalyst], and dexamethasone [DPd] as another option.

KRISHNAN: [Are there] any other takers for DPd instead? It sounds like everyone would agree with daratumumab, but its really what the partner would be. Would anyone pick DPd?

CHAND: I tend to use more DPd compared [with] DKd, because in my experience, scheduling and monitoring is a little easier on this regimen. It tends to work well in patients who are refractory to lenalidomide. I just find it more tolerable. The cytopenias are a little bit less compared [with] the DKd, too.

AMBIKA: I tend to use more DPd, toofor the same reasons as [others mentioned]and use carfilzomib, cyclophosphamide, and dexamethasone [KCd] as the next-line [treatment], like carfilzomib plus cyclophosphamide. I went through that route in a few patients and they did OK.

DEKKER: I typically use carfilzomib. [Patients] come to [the] infusion center already, so they will get carfilzomib as well. Plus, carfilzomib is a potentially more powerful agent, and I use it once a week. If [patients] develop cardiac toxicities [within the first 2 or 3 weeks], I back off. If they dont, they typically would do well and tolerate it for a long time.

CHAUDHARY: Myelosuppression is less with DPd, in my experience, if you dose reduce the pomalidomide.

KRISHNAN: It sounds like were pretty much split [between] DPd and DKd, both being valid regimens in that early 1- to 3-[year] relapse setting. What Im hearing from people is to pick your adverse events [AEs], as well, and Im guessing [that] if someone had prior cardiac history, more clinicians would [choose to use] DPd. But let me ask a more challenging question. Ive not heard a single person say IPd [isatuximab-irfc (Sarclisa), pomalidomide, dexamethasone] or IKd [isatuximab, carfilzomib, dexamethasone]. Is anyone using isatuximab?

MURAD: Thats our preferred drug, but thats definitely a reasonable option. I dont think theres any problem with carfilzomib.

DEKKER: I use daratumumab and isatuximab. Clearly, subcutaneous administration is a plus, but I had a few patients who had a cutaneous reaction or had skin conditions, so I decided to go with isatuximab.

KRISHNAN: Do most [of you] feel theyre comparable, or do [you] feel that theres a difference?

DEKKER: I think theyre probably comparable. I do think [that] sometimes later products may have some advantages, because they know the issues with the original product and tried to tweak the molecule a little bit. So theoretically, I would say isatuximab may be a bit better, but the problem is daratumumab is good enough on its own, so Im doubtful we will find much of the difference. We could keep analyzing the data and find a subtype, a subgroup here or there, or a special population that will be beneficial. But for both [medications, it is] likely all the data will come down to the same ballpark.

KRISHNAN: Im just curious, Dr Dekker, when you say you think isatuximab is better, is it in terms of [AEs] or efficacy?

DEKKER: Both, because again, they look at the molecule, they see off-target effects, and they see where the escape mechanisms are. So when they manufacture the molecule, all this minor tweaking in the design may help to both improve efficacy and decrease toxicity. But how clinically significant that is, how truly that will translate into something meaningful in clinical practice without head-to-head datathat will be impossible to determine.

KRISHNAN: So if I could summarize, most [of you] are convinced [of using] CD38 antibody without, and finding them interchangeable depending on their practice and some specific patient issues. Then its really the partner to that antibody, right?

MUKHERJEE: Yeah, Im comfortable with using daratumumab now and usually do introduce that in the second line. Depending on the other comorbidities of the patient, if they have cardiac issues, then I would go with pomalidomide. If not, then carfilzomib. Im comfortable with daratumumab, but Im not that comfortable with isatuximab yet.

KRISHNAN: Thats interesting. I will give you a look to the future. Theres a phase 3 trial ongoing, [comparing] DPd[with] teclistamab-cqyv [Tecvayli], pomalidomide, and dexamethasone, so that will be interestingthe T-cell engager, the new drug that just got approved, then being moved into that early relapse setting. I think many of you are familiar with the CARTITUDE-1 trial [NCT03548207], also in the earlier relapse setting.1

What will be interesting [is that in 2024 or 2025], myeloma may look completely different. We [may] see T-cell engaging therapy moved up earlier, in part because the CD38 antibodies are [also] going to be moved up even earlier, in terms of their use in induction therapy. I think that is the challenge in myeloma.

DISCUSSION QUESTION

KRISHNAN: I think the [PFS data for these regimens are] what people responded to, [those] who wanted to use carfilzomib as the partner to CD38. In the IKEMA trial [NCT03275285], which compared IKd vs Kd [carfilzomib and dexamethasone], the PFS is decent and youre getting almost 3.5 years out of a first relapse regimen [From the Data2].

In the CANDOR trial [NCT03158688], [the PFS is approximately] 2.5 years, [comparing DKd vs Kd].3 And then [the PFS] goes down from there in the CASTOR [NCT02136134], ICARIA-MM [NCT02990338], APOLLO [NCT03180736], and OPTIMISMM trials [NCT01734928].4-7 Interestinglyand I use a lot of DPdif you compare the PFS, its not as great at [approximately 1] year based on the APOLLO study, and IPd is the same at [approximately 1] year.5,6

DISCUSSION QUESTION

KRISHNAN: This patient did have some mild renal impairment, [as well as] the genetic risk with the [1q21 gain]. It sounds like that would push you a little bit more, as well.

LASHKARI: The 1 issue I think a lot of us have who see these patients with myeloma is that carfilzomib is a great drug, but its not without some of its own AEs in terms of cytopenias, fluid retention, and sometimes infusion reactions. And for the [patients who] are just in your office all the time, I feel for them. Thats another potential barrier, especially if youre dealing with patients who may not be as robust as others.

That is a big factor that plays into my thinking for maybe not using carfilzomib at this time. Maybe I should be changing my mind if the dataas we saw with the 2 trials evaluating carfilzomib with daratumumab or isatuximabare truly what you get out of it. Maybe that is a better option, but it may be a slightly harder sell for patients, especially those [who] value their quality of life and the amount of time that theyre not spending at your office.

KRISHNAN: I do think its a potent regimen. I tend to use it in younger patients, because I do think, in the CANDOR study, [most] of the deaths were in patients [older than] 65 [years], and more infectious death.3 In older patients, I tend to be a little more cautious about using it, and I only do it in older patients when my back is against the wall and they have really aggressive disease.

Otherwise, I do use it in younger patients with aggressive disease. In other younger patients, I try to, but to your point, a lot of younger patients tend to still be working, and coming into the office even once a week can be challenging. So lifestyle and patient preference also play an important role.

REFERENCES

1. Martin T, Usmani SZ, Berdeja JG, et al. Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up.J Clin Oncol. 2022;JCO2200842. doi:10.1200/JCO.22.00842

2. Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial.Lancet. 2021;397(10292):2361-2371. doi:10.1016/S0140-6736(21)00592-4

3. Usmani SZ, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study.Lancet Oncol. 2022;23(1):65-76. doi:10.1016/S1470-2045(21)00579-9

4. Spencer A, Lentzsch S, Weisel K, et al. Daratumumab plus bortezomib and dexamethasoneversusbortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR.Haematologica. 2018;103(12):2079-2087. doi:10.3324/haematol.2018.194118

5. Richardson PG, Perrot A, San-Miguel J, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study. Lancet Oncol. 2022;23(3):416-427. doi:10.1016/S1470-2045(22)00019-5

6. Dimopoulos MA, Terpos E, Boccadoro M, et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial.Lancet Oncol. 2021;22(6):801-812. doi:10.1016/S1470-2045(21)00128-5

7. Richardson PG, Oriol A, Beksac M, et al. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial.Lancet Oncol. 2019;20(6):781-794. doi:10.1016/S1470-2045(19)30152-4

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Roundtable Discussion: Krishnan Debates the Rationale For ... - Targeted Oncology

Multiple myeloma is a type of blood cancer that affects the plasma cells, which are responsible for producing antibodies in the body. Being one of the most common blood cancer, it requires timely diagnosis and treatment. Over the years, there have been many advances in the diagnosis and treatment of multiple myeloma, leading to better outcomes for patients.

Plasma cells, a subset of white blood cells that make antibodies, are the target of the malignancy known as multiple myeloma. Early diagnosis and treatment of multiple myeloma are crucial for improving outcomes and enhancing chances of survival," says Dr S Jayanthi, Senior Pediatric Oncologist, Kamineni Hospitals, Hyderabad.

The latest treatment approaches to enhance the chances of diagnosing multiple myeloma are offering promising new treatments. Many multiple myeloma patients receive chemotherapy in order to reduce or eliminate their cancer cells. In some cases, chemotherapy may also lead to cancer remission. However, long term cancer control can often be difficult to achieve with this approach alone. Allogeneic bone marrow transplantation is a new treatment option that has shown promise for many multiple myeloma patients and is considered a more aggressive approach than just chemotherapy alone," adds Dr Jayanthi.

Early diagnosis and treatment of multiple myeloma are essential for improving outcomes and enhancing chances of survival. The latest treatment approaches, such as advanced imaging tests, biopsy, genetic testing, targeted therapies, and immunotherapy, can help to diagnose multiple myeloma and provide personalized treatment plans for better outcomes.

Advancements in imaging technology, such as PET-CT and MRI scans have allowed for more precise assessment and can detect myeloma lesions earlier than traditional X-rays, which can be critical for early diagnosis and effective treatment. Another newer advance in the treatment of multiple myeloma is the use of precision medicine. Precision medicine involves using genetic testing to identify the specific genetic mutations that are driving the growth of myeloma cells. Once these mutations are identified, targeted therapies can be used to block their effects and stop cancer from growing. This approach can lead to more personalized and effective treatment for each individual patient," says Dr Ashish Dixit, Consultant, Haematology, Haemato Oncology & Bone Marrow Transplantation, Manipal Hospital Old Airport Road.

Targeted therapies are newer treatment options for multiple myeloma. These drugs are designed to target specific proteins or pathways that are essential for the growth and survival of myeloma cells. An example of targeted therapy for multiple myeloma can be proteasome inhibitors, such as bortezomib. These drugs block the breakdown of proteins in myeloma cells, leading to their death.

Another newer treatment option for multiple myeloma is monoclonal antibodies, which are designed to target specific proteins on the surface of myeloma cells. Daratumumab is an example of a monoclonal antibody used in treating multiple myeloma. This drug helps the immune system recognize and attack myeloma cells more effectively," adds Dr Dixit.

Stem cell transplantation is one of the standard treatments for multiple myeloma. Stem cell transplantation involves collecting healthy stem cells from the patient or a donor, and then administering high doses of chemotherapy to kill cancer cells. The healthy stem cells are then infused back into the patients body, helping to restore the immune system and blood cell production.

Targeted Immunotherapy is a treatment option that uses the bodys immune system to fight cancer cells. One type of immunotherapy used in multiple myeloma is called CAR T-cell therapy. This treatment involves modifying the patients own T-cells in a laboratory so that they can recognize and destroy myeloma cells more effectively," opines Dr Dixit.

These newer advances in the diagnosis and treatment of multiple myeloma offer hope for patients with this disease. With continued research and development, we may see even more effective treatments in the future. It is important for patients with multiple myeloma to work closely with their doctors to determine the best course of treatment for their individual needs.

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Improving Multiple Myeloma Diagnosis with Advanced Treatments - News18

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Sam Neill is back working, despite rare cancer diagnosis.

Kiwi actor Sam Neill, who revealed he has been receiving treatment for a rare form of blood cancer, is very well and back at work.

Neills personal assistant Lauren Folk Major thanked the fans for their support after he told the Guardian he is being treated for angioimmunoblastic T-cell lymphoma (AITL).

He is very well and back at work starring opposite Annette Bening in the upcoming limited series, Apples Never Fall, said Falk Major.

Neill is releasing a memoir on Tuesday titled Did I Ever Tell You This?.

READ MORE:* Kiwi actor Sam Neill says he's being treated for blood cancer* Sam Neill says Michael Fassbender 'took offence' at having a rooster named after him* Peter Rabbit director spills the berries on Kiwi actor Sam Neill* Sam Neill eats plastic bag to save turtles

Neill told the Guardian his book is not a cancer memoir, but rather his illness forms what he calls a spiral thread throughout the story.

I cant pretend that the last year hasnt had its dark moments, he said. But those dark moments throw the light into sharp relief, you know, and have made me grateful for every day and immensely grateful for all my friends. Just pleased to be alive.

What is angioimmunoblastic T-cell lymphoma?

Leukaemia and blood cancer New Zealand says lymphomas are a relative common form of cancer in Aotearoa-New Zealand, affecting about 800 Kiwis every year. There are more than 50 kinds of lymphoma, some are very rare.

The cancer Neill is receiving treatment for is a rare, often aggressive, or fast-growing, form of lymphoma.

This is one of a number of cancers that attack the immune system via the lymph nodes. The lymphatic system filters lymphatic fluid and white blood cells around the body, helping your body fight disease.

While non-life-threatening illnesses such as strep throat and chickenpox can cause our lymph nodes can swell, swelling can also, on rare occasions, signal the presence of cancer.

There are two types of Lymphoma: Hodgkins and Non Hodgkins, the chief difference being which kind of lymphocyte, or white blood cell, the cancer attacks. Cancer Research UK describes AITL as a non-Hodgkins Lymphoma that affects the T-cells, which fight infection. Because it affects the T-cells, AITL can impact organs beyond the lymphatic system.

Governor General of New Zealand/

Dame Cindy Kiro confers Sam Neill as a Knight Companion of the New Zealand order of Merit.

Symptoms can include fevers, night sweats, skin rashes, and a form of anaemia, which results from the bodys immune system attacking its own cells and tissues.

The Lymphoma Research Foundation says diagnosis is most commonly by biopsy, and PET and MRI scans. Treatment is with corticosteroids, such as prednisone, and chemotherapy. Some research shows stem-cell therapy has encouraging outcomes.

According to his book, Neills lymphoma responded to a new drug therapy after chemo failed the first time round. His cancer is now in remission.

Kiwi actor and winemaker Sir Sam Neill, of Jurassic Park and The Piano fame, is the proprietor of Two Paddocks, a family vineyard based in Central Otago. He talks about the country's unique wine.

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Actor Sam Neill 'very well', back working, as rare, aggressive cancer ... - Stuff

To find the best pet insurance we reviewed each companys policy wording and used data provided by PetInsurer.com to score each pet insurance company based on the following:

Pet insurance rates: 40% of score. We calculated average rates for plans with $5,000 or unlimited coverage, a $100 deductible and an 80% reimbursement level, or the closest options available.

Special waiting period: 10% of score. Many pet insurance companies have a special waiting period for problems such as cruciate ligament issues and hip dysplasia. Plans that had no waiting period, a waiting period of six months or less, or the ability to have the waiting period waived scored higher.

Direct payment to vet: 10% of score. Pet insurance companies that have the ability to pay a vet directly earned points.

24/7 vet health line: 10% of score. Insurers that provide access to a 24/7 vet health line scored in this category.

Routine wellness plans: 10% of score. Insurers that offer wellness plans, either included with a plan or as a rider, earned points.

Dental coverage for illness: 10% of score. While most insurers cover dental accidents, not all insurers cover dental illnesses, such as gum disease or cleanings. Plans with more extensive dental coverage scored higher.

Pet ownership assistance: 5% of score. Insurers that include coverage for pet owner expenses, such as advertising and reward for lost pets, boarding for medical emergencies, end of life expenses and/or vacation cancellation, scored in this category.

Any discount: 5% of score. Insurers that offer any kind of discount, including a multi-pet discount, healthy pet discount, loyalty discount, etc., earned points.

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Pets Plus Us Pet Health Insurance Review 2023 Forbes Advisor ... - Forbes

Professor of Genetics at Harvard Medical School, a veteran geroscientist, and a serial entrepreneur, George Church hardly needs an introduction. While we are always happy to discuss the present and future of geroscience with him, this interview focuses on the two gene therapy papers that he recently co-authored, which drew a lot of attention due to their spectacular and surprising results. In this interview, Prof. Church interprets these results and gives his opinions on a range of longevity-related topics, such as cellular reprogramming and supplements.

Thats a good question, especially given that we were using this huge vector. The whole point of cytomegalovirus is that it can package a lot more. I think its just that these experiments are not cheap, including the mice. What is distinctive about both papers is that they have a Kaplan-Meier plot, and those are more expensive than just showing some reversal of physiological decay or of an age-related disease. Both groups are thinking about combinations, they just havent done all of them yet.

Those are fairly independent pathways. There are arguably ten major pathways of aging, and I think you need to get all ten pathways if you want to impact longevity beyond a certain point. Its been estimated that doing just one of those ten pathways might get you two years of life extension in humans and maybe a few months in mice. But, if you develop something that impacts multiple pathways, some combination drug, that will be very interesting to see when we get to that.

I think the original explanation is that cachexia is muscle wasting that accompanies a lot of aging. You could argue thats just a late-stage thing, and to do real aging reversal youd want to get to the earlier stages, or you could argue that this is one of the ten pathways, and you want to have that part of a combination, but the answer is that its still not clear why it works in itself.

Its one of the mechanisms that cancer can cause death by, but there are others. Cancer can cause death by making it hard to breathe. It can screw up almost any physiological process, depending on where it starts and where it metastasizes, but muscle wasting can be a product of fairly normal aging without cancer as well. Seems like its a nice tool to have in your toolbelt, but I admit it is a little surprising that it works by itself.

First, there are effects that we do know about. If you give a long steady dose, it will increase the probability of tumorigenesis. It also sets you up for additional genetic and epigenetic changes that can make an even more serious cancer. But, if you give intermittent doses, its like with Yamanaka factors in the second study: if you give too much, cells could go back too far in time. So, I think its all about moderation.

The other thing that was done in germline experiments, or earlier animal models, is to use specific safeguards against cancer so that when you then introduce the telomerase, you can express it at higher levels and for longer periods of time. For instance, messing around with the p16 and p53 pathways, i.e., having extra copies of tumor suppressors, can protect you against certain forms of cancer and allow you to use things that would otherwise put you at risk.

Its all about resources. Both those companies are scrappy, young, underfunded, but they make up for it in creativity and delivery. Those are the only two gene therapy papers that I know of that show significant Kaplan-Meier plots. And I really like the gene therapy approach that they share, because you can target alleles, splice isoforms, and gene family members (paralogs). This is something thats very hard to do with small molecules, but very easy to do with either protein or gene therapies.

The slight advantage of gene therapies over protein therapies is that you have a few ways of rigging the specificity. You can have specificity of the vector, specificity of the nucleic acid, and finally, specificity of the protein. With proteins, you only have the latter.

The only thing I dont like about gene therapies is the cost, but one positive side of the COVID dilemma was that we tested five different vaccines that were formulated in the form of a gene therapy on billions of people and got the price down to as low as 2 dollars for one of those five. Its a whole new ballgame now if you have a large market, and I think pandemics and aging are the largest.

We had already done three genes at once at my lab and Rejuvenate Bio. Those were different from the OSK Yamanaka factors. The latter are transcription factors that need to be delivered to the nucleus, while the other set that we had, TGF beta receptor 2 in soluble form, Klotho, and FGF21, could be soluble, secreted, hence they could go into the interstitial, intercellular matrix, or they could go out into the blood. In a certain sense, it requires less delivery, or less ubiquitous delivery of the nucleic acid, because then the proteins do some of the delivery.

Thats the fundamental difference between those two. The significance of using the OSK is that this was the best example that we had of rejuvenation, as opposed to just fighting the symptoms of some age-related disease, making your muscles hurt less or something. This was truly rejuvenating ancient cells all the way back to embryo.

So, if you can control that, dial it up and down, it has some promise. This encouraged several groups, including Altos Labs, which I worked with briefly (many of my alumni are core members of Altos Labs). It is also one of the things that encouraged our collaboration with David Sinclair.

But, except for Rejuvenate Bio, so far, all of those are fairly distantly related to longevity. They might cure something like a crushed optic nerve, but damage to the eye is not aging, certainly not longevity. Now, this wasnt merely the Kaplan-Meier plot where you could see extended life. The injection occurred at the age of 124 weeks. For a mouse, its very late in life. Half of the mice in the cohort are already dead at that point.

The logic behind this was that if you do it as late as possible and show that it still has an effect, thats very encouraging. It broadens the market, thats one way of thinking about it, but it also tells you that you are really getting a reversal as opposed to delay, and thats a fundamental difference. Many drugs that are considered cures are reversing something, but people somehow put reversing aging in a special category, like breaking the sound barrier. However, just like breaking the sound barrier was easy enough to do once we figured it out, reversal of fundamental epigenetic programs that are a natural part of development and aging starts looking easier than it originally did.

There have been two major camps in aging since long ago. One says that aging happens due to damage, to proteins, lipids, RNA, and DNA, and that you have to go in there with your repair kit and fix it as a therapist. The other camp says that its all epigenetic, and that if you convince the cell that its young, it will get its own toolkit out and start repairing as much as it can. Some things are beyond repair. If you delete all copies of a tumor suppressor, thats not something a young cell can repair. But most things are fixable with epigenetics at least, thats how the second hypothesis goes.

I believe in a hybrid model. I think most of the work can be done epigenetically. A surprising amount of it can be done via the bloodstream, but probably not all of it. Then, theres a residual amount that you can fix with the Yamanaka factors and another residual amount that you can fix by restoring genes.

Since we do the epigenetic reprogramming by adding in genes, its not that fundamental a difference between adding in genes that will go into the blood, adding genes that will reprogram the nucleus, and adding genes that are missing, like tumor suppressors. In a certain sense, they are all addressable by multiplex gene therapy. Thats why being able to either use multiple rounds of dosing or to have bigger vectors will become increasingly important.

I think there are subtle but important differences between anti-aging drugs and drugs that improve biomarkers in the way that statins improve cholesterol. That doesnt mean such drugs increase longevity, just that they improve this one biochemical. It could actually hurt you; for instance, it could improve cardiovascular chances for some subset of the population, but for another subset, it could hasten muscle pain.

So, affecting biomarkers is one thing. Reversing diseases of aging is different. You could do it just by addressing that particular disease, or you could do it more broadly, affecting multiple diseases. You might get FDA approval for one of them, but its actually affecting multiple ones, and maybe acting preventatively. Say, there might be a cure for muscle wasting that helps prevent a variety of diseases.

Finally, youre really at the core of aging when you reprogram shared elements with good feedback systems that already exist in the body or with feedback systems that you introduce as part of the therapy.

The thing about clinical trials is that you ideally minimize talking about them before theyre done. This is a second animal trial. We did it in mice already, and it looked good. With the dogs, its not just an animal trial, its also a product, a veterinary product. I understand that some of the pet owners involved have said good things, but, of course, you have to be very cautious with anecdotal evidence. There could be wishful thinking, placebo effect involved. These are randomized clinical trials, so you really wont know until you break blinding at the end.

But the nice thing about veterinary clinical trials is that theyre typically much faster than human clinical trials. COVID-19 trials were an exception, 12 months, but most human clinical trials last about 10 years, and most veterinary trials are more like 18 months. So, well know soon.

We could have gone straight from mice to humans, but we decided to create a veterinary product. People spend a fair amount of money on end of life in dogs, they even clone dogs, but of course, a clone is not what you want. So, its valuable to have two or more animal preclinical trials before you go into clinical trials. Even though were looking into specific diseases, for instance, the mitral valve disease in spaniels, its not limited to that. We hope that it will hit many different diseases. Weve tested it in about five or six different diseases already, in mice and dogs.

To move this into humans, you use the same genes. You might use a human version of them, just like you might switch from mouse to dog genes, but other than that, mode of delivery. You might also change the vector. We use AAV vectors, which is the oldest approved vector and one of the most popular ones. However, dogs have natural immunity to most of the popular AAV vectors.

Thats clearly solvable. Its even solvable for redosing. One of the advantages of certain gene therapies is that you dont have to redose. You might have a once-and-done, lifetime expression, but a couple of my companies are working on improving the AAV delivery. Shape Therapeutics and Dyno Therapeutics are both making quite a progress on this. So, you can make radically different capsids that have radically different tissue tropisms and immune evasion. You basically make viruses that dont exist in the wild or in previous pharmaceuticals, and you can probably keep generating those things for quite a while.

First, with dogs, you can get a lot of feedback on how to maximize your chances of success. Second, its a product, so you can make a profit on the first product to pay for the development of the second product. Human clinical trials are expensive. You could do it by investment, but that would result in dilution of the original founders stake in it.

Also, dogs are just a particularly good intermediate between mice and humans, because they live in a human environment, they have some compatible behavioral traits and eating habits. You can identify personality changes, subtle behavioral changes that you dont identify in mice, because you dont cohabit with them like you do with dogs.

None of this means that we couldnt go directly to humans, its just that failures in human trials can put a damper on the whole field. I hope that all people in the field do their homework and dont rush trials, because they can screw it up for us. Were trying not to screw it up for them, and, hopefully, that will be reciprocated.

I co-founded 46 companies. Im on the scientific advisory board of a few more. Seven of them are related to aging reversal and longevity. They all involve pre-clinical and clinical trials. Some are on nutritional supplements, which you can sell without FDA approval, but nevertheless, theyre doing trials, and thats a strong preference for my involvement in a company: they have to be willing and planning to do, and also have the resources to do, clinical trials, even if not legally required.

I think the whole field is very healthy economically and scientifically. We have passed through multiple valleys of death. Were now in the solid science phase, and this field is going to be very impactful, maybe more impactful than any other pharmaceuticals in history, including even antibiotics, because our very ability to fight off diseases is age-related. Almost every single form of human morbidity and mortality has an age-related component to it. If you want to have a pleiotropic effect on many different diseases, this is the way to go.

So, it seems like a good choice. It also has a good chance of being cost-effective enough. Im not promising this on behalf of any of my companies, but since manufacturers of COVID vaccines can get gene therapy to be as cheap as two dollars a dose, others can do that as well, and thats important to me from the standpoint of equitable distribution of technology. Its not about can we develop a billion-dollar drug? Rather, its can we distribute it to everyone who needs it? And the same way that we got the price of DNA sequencing down seven orders of magnitude, 20-million-fold, I think we need to at least consider that for every new medical technology.

Yes, and I was referring to them when I said theyre willing to do clinical trials even though they are not required to do so.

I think we need to be very cautious about supplements that do not go through clinical trials and also about what trials they went through. If you do a clinical trial on ALS or some other degenerative disease, then thats all youre addressing. Youre not addressing the broader population. And, you have to be cautious, because some supplements have been shown to be detrimental if taken for prolonged periods in particular individuals that may have a pharmacological predisposition.

For example, some encourage cancer. And thats true for all things you put in your body. Just because your grandparents got away with it doesnt mean that its going to work, especially as we now have a more complex environment with a lot of other toxins.

Also, because were staying employed later and later in life, we need to reevaluate the things that were generally recognized as safe. So, Im very enthusiastic about testing and retesting things that have been accepted without formal clinical trials. Theres a lot of placebo effects, long-term effects, and wishful thinking that we need to put to the test. I hope those two companies continue along that pathway.

Im a scientific advisor. We shouldnt ignore companies that need advice, otherwise, they will be operating without advice. As long as theyre doing clinical trials, theyve got my attention.

I think we really need to hit all ten pathways and think about their interactions. In my opinion, the easiest way to go from a hypothesis or a pile of molecular data to a therapy is via gene therapy. In a couple of weeks, you can essentially go from a new research article to a therapy and get that therapy into mice.

So, Im particularly excited about those directions. We dont know yet whether it should be cell-autonomous or something that spreads through the blood, probably both. Im excited about the possibility that this could be low-cost for equitable distribution.All those things are clustered around this multi-drug therapy, which I think is fairly well-validated in other cases: multi-drug antibiotics, multivalent antivirals, cancer, some other diseases as well.

Yes, except you have to test them all in vitro and in animal models, in the exact formulation that you want to use, even if the ingredients were already tested individually. Sometimes with gene therapy, you cant test the very exact molecular form, because theres a difference between the animal form and the human form. But, other than that, everything should be as close as possible.

Its not either or. Cells can deliver genes and proteins. The advantage of cell therapy in principle is that you can debug the gene therapy ex vivo and then deliver it. For example, if you apply gene therapy in vivo to a billion cells, youve got a billion chances for genetic mischief, but with cell therapies, especially clonal cell therapies, you can debug it and make sure this is genetically and epigenetically what you want, that all cells are basically identical.

The downside of it is that many cells just dont deliver very well. For example, neurons are highly connected. Maybe you can deliver a few neuronal stem cells, including into parts of the brain that normally dont have neuronal stem cells, but you also want to keep most of your connections intact and not replace them with some generic neuronal progenitor. The bottom line is that theres room for a lot of different strategies and innovations.

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Professor of Genetics at Harvard Medical School, a veteran geroscientist, and a serial entrepreneur, George Church hardly needs an introduction....

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Prof. George Church on Cellular Reprogramming and Longevity - Lifespan.io News

Blad J, Samson D, Reece D, Apperley J, Bjrkstrand B, Gahrton G, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998;102:111523.

Article PubMed Google Scholar

Durie BG, Harousseau JL, Miguel JS, Blad J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:146773.

Article CAS PubMed Google Scholar

Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17:e328e46.

Article PubMed Google Scholar

Anderson KC, Alsina M, Atanackovic D, Biermann JS, Chandler JC, Costello C, et al. NCCN Guidelines Insights: Multiple Myeloma, Version 3.2016. J Natl Compr Canc Netw. 2016;14:389400.

Article CAS PubMed PubMed Central Google Scholar

Jakubowiak AJ, Dytfeld D, Griffith KA, Lebovic D, Vesole DH, Jagannath S, et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood 2012;120:18019.

Article CAS PubMed PubMed Central Google Scholar

Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:178291.

Article CAS PubMed Google Scholar

Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet 2017;389:51927.

Article CAS PubMed Google Scholar

McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C, Tosi P, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: A meta-analysis. J Clin Oncol. 2017;35:327989.

Article CAS PubMed PubMed Central Google Scholar

Keats JJ, Chesi M, Egan JB, Garbitt VM, Palmer SE, Braggio E, et al. Clonal competition with alternating dominance in multiple myeloma. Blood 2012;120:106776.

Article CAS PubMed PubMed Central Google Scholar

Mailankody S, Korde N, Lesokhin AM, Lendvai N, Hassoun H, Stetler-Stevenson M, et al. Minimal residual disease in multiple myeloma: Bringing the bench to the bedside. Nat Rev Clin Oncol. 2015;12:28695.

Article PubMed PubMed Central Google Scholar

Zamagni E, Nanni C, Patriarca F, Englaro E, Castellucci P, Geatti O, et al. A prospective comparison of 18F-fluorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance imaging and whole-body planar radiographs in the assessment of bone disease in newly diagnosed multiple myeloma. Haematologica 2007;92:505.

Article PubMed Google Scholar

Moreau P, Attal M, Caillot D, Macro M, Karlin L, Garderet L, et al. Prospective Evaluation of Magnetic Resonance Imaging and [(18)F]Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography at Diagnosis and Before Maintenance Therapy in Symptomatic Patients With Multiple Myeloma Included in the IFM/DFCI 2009 Trial: Results of the IMAJEM Study. J Clin Oncol. 2017;35:29118.

Article CAS PubMed PubMed Central Google Scholar

Bartel TB, Haessler J, Brown TL, Shaughnessy JD Jr, van Rhee F, Anaissie E, et al. F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma. Blood 2009;114:206876.

Article CAS PubMed PubMed Central Google Scholar

Usmani SZ, Mitchell A, Waheed S, Crowley J, Hoering A, Petty N, et al. Prognostic implications of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3. Blood 2013;121:181923.

Article CAS PubMed PubMed Central Google Scholar

Cav H, Van Der Werff Ten Bosch J, Suciu S, Guidal C, Waterkeyn C, Otten J, et al. Clinical Significance of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia. N. Engl J Med. 1998;339:5918.

Article PubMed Google Scholar

Grimwade D, Jovanovic JV, Hills RK, Nugent EA, Patel Y, Flora R, et al. Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy. J Clin Oncol. 2009;27:36508.

Article CAS PubMed Google Scholar

Kovacs G, Robrecht S, Fink AM, Bahlo J, Cramer P, Von Tresckow J, et al. Minimal residual disease assessment improves prediction of outcome in patients with chronic lymphocytic leukemia (CLL) who achieve partial response: Comprehensive analysis of two phase III studies of the German CLL study group. J Clin Oncol. 2016;34:375865.

Article CAS PubMed Google Scholar

Paiva B, Gutirrez NC, Rosiol L, Vdriales MB, Montalbn M, Martnez-Lpez J, et al. High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma. Blood 2012;119:68791.

Article CAS PubMed Google Scholar

Flores-Montero J, Sanoja-Flores L, Paiva B, Puig N, Garcia-Sanchez O, Bottcher S, et al. Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia 2017;31:2094103.

Article CAS PubMed PubMed Central Google Scholar

Paiva B, Puig N, Cedena MT, Rosinol L, Cordon L, Vidriales MB, et al. Measurable residual disease by next-generation flow cytometry in multiple myeloma. J Clin Oncol. 2020;38:78492.

Article CAS PubMed Google Scholar

Martinez-Lopez J, Lahuerta JJ, Pepin F, Gonzalez M, Barrio S, Ayala R, et al. Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood 2014;123:30739.

Article CAS PubMed PubMed Central Google Scholar

Landgren O, Rustad EH. Meeting report: Advances in minimal residual disease testing in multiple myeloma 2018. Adv Cell Gene Ther. 2019;2:e26.

Article Google Scholar

Munshi NC, Avet-Loiseau H, Rawstron AC, Owen RG, Child JA, Thakurta A, et al. Association of minimal residual disease with superior survival outcomes in patients with multiple myeloma. JAMA Oncol. 2017;3:28.

Article PubMed PubMed Central Google Scholar

Munshi NC, Avet-Loiseau H, Anderson KC, Neri P, Paiva B, Samur M, et al. A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma. Blood Adv. 2020;4:598899.

Article PubMed PubMed Central Google Scholar

Rawstron AC, Child JA, De Tute RM, Davies FE, Gregory WM, Bell SE, et al. Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: Impact on outcome in the medical research council myeloma ix study. J Clin Oncol. 2013;31:25407.

Article PubMed Google Scholar

Perrot A, Lauwers-Cances V, Corre J, Robillard N, Hulin C, Chretien ML, et al. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood 2018;132:245664.

Article CAS PubMed PubMed Central Google Scholar

Rawstron AC, Gregory WM, de Tute RM, Davies FE, Bell SE, Drayson MT, et al. Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction. Blood 2015;125:19325.

Article CAS PubMed PubMed Central Google Scholar

Lahuerta JJ, Paiva B, Vidriales MB, Cordon L, Cedena MT, Puig N, et al. Depth of response in multiple myeloma: A pooled analysis of three PETHEMA/GEM clinical trials. J Clin Oncol. 2017;35:290010.

Article CAS PubMed Google Scholar

de Tute RM, Rawstron AC, Gregory WM, Child JA, Davies FE, Bell SE, et al. Minimal residual disease following autologous stem cell transplant in myeloma: impact on outcome is independent of induction regimen. Haematologica 2016;101:e6971.

Article PubMed PubMed Central Google Scholar

Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:14252.

Article PubMed Google Scholar

Lonial S, Anderson KC. Association of response endpoints with survival outcomes in multiple myeloma. Leukemia 2014;28:25868.

Article CAS PubMed Google Scholar

Avet-Loiseau H, Ludwig H, Landgren O, Paiva B, Morris C, Yang H, et al. Minimal residual disease status as a surrogate endpoint for progression-free survival in newly diagnosed multiple myeloma studies: A meta-analysis. Clin Lymphoma Myeloma Leuk. 2020;20:e30e7.

Article PubMed Google Scholar

Facon T, Lee JH, Moreau P, Niesvizky R, Dimopoulos M, Hajek R, et al. Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma. Blood 2019;133:195363.

Article CAS PubMed Google Scholar

Dimopoulos MA, San-Miguel J, Belch A, White D, Benboubker L, Cook G, et al. Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: Updated analysis of POLLUX. Haematologica 2018;103:208896.

Article CAS PubMed PubMed Central Google Scholar

Ching T, Duncan ME, Newman-Eerkes T, McWhorter MME, Tracy JM, Steen MS, et al. Analytical evaluation of the clonoSEQ Assay for establishing measurable (minimal) residual disease in acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. BMC Cancer. 2020;20:612.

Article CAS PubMed PubMed Central Google Scholar

Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised international staging system for multiple myeloma: A report from international myeloma working group. J Clin Oncol. 2015;33:28639.

Article CAS PubMed PubMed Central Google Scholar

Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 2009;23:221021.

Article CAS PubMed PubMed Central Google Scholar

Schmidt TM, Fonseca R, Usmani SZ. Chromosome 1q21 abnormalities in multiple myeloma. Blood Cancer J. 2021;11:83.

Article PubMed PubMed Central Google Scholar

Campbell BA, Scarisbrick JJ, Kim YH, Wilcox RA, McCormack C, Prince HM. Time to next treatment as a meaningful endpoint for trials of primary cutaneous lymphoma. Cancers (Basel). 2020;12:2311.

Article CAS PubMed Google Scholar

Goicoechea I, Puig N, Cedena M-T, Burgos L, Cordn L, Vidriales M-B, et al. Deep MRD profiling defines outcome and unveils different modes of treatment resistance in standard- and high-risk myeloma. Blood 2021;137:4960.

Article CAS PubMed Google Scholar

Schinke C, Hoering A, Wang H, Carlton V, Thanandrarajan S, Deshpande S, et al. The prognostic value of the depth of response in multiple myeloma depends on the time of assessment, risk status and molecular subtype. Haematologica 2017;102:e313e6.

Article CAS PubMed PubMed Central Google Scholar

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Integrated analysis of next generation sequencing minimal residual ... - Nature.com

When treating patients with mantle cell lymphoma (MCL), early identification and appropriate frontline therapy remains critical, and therapies may vary for those 65 years and older compared with patients under the age of 65, with several additional factomd andersonrs also having a role in approaching treatment options for a new patient in the clinic, according to Michael L. Wang, MD.

Wang, a professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, explained the factors he considers when determining the optimal therapeutic strategy for patients with MCL during the 27th AnnualInternational Congress on Hematologic Malignancies: Focus on Leukemias, Lymphomas, and Myeloma.1

Although age under 65 years and 65 years and older are used to stratify patients, Wang noted that translating these criteria to the clinic, a range of plus or minus 5 years can be used to adjust for care. Factors to consider include performance score. For example, Wang cited a very healthy 70-year-old patient or a patient who is 60 years with comorbidities and a low performance score.In addition to determining urgency of care, examining the patients cardiac history is crucial with renal and bone marrow function also being key factors. Treatment history with response from last therapy, duration of prior treatments, and history ofBruton tyrosine kinase(BTK) inhibitors should also be considered along with further parameters such as toxicities and transplant history.

Clinically you absolutely want to know the patients cardiac history and you want to know their kidney history, Wang said. Cardiac history is very important; I will not feel comfortable starting the patient with a BTK inhibitor without getting [a] cardiology consultation, electrocardiogram, stress tests, [and] echocardiogram.

Attention should be given to the organ system as a spleen over 20 cm may rupture and gastrointestinal (GI) bleeding can be severe. Central nervous system involvement when it is high-risk should be monitored as well.

Gastric MCL is quite commonly seen and sometimes you do an endoscopy but find that [the patient] had a volcano sitting theretheres a crater and near the crater theres a big artery ready to burst.

Examining pathology is key to determine if the MCL is pleomorphic or blastoid, and as MCL has 2 presentations, one of them being chronic lymphocytic leukemia, and this needs to be specified. Wang also noted he will run laboratory analyses such as creatine and lymphocytosis tests, and staging for MCL is more up in the air than staging is for other types of lymphoma, at MD Anderson Cancer Center, he will confirm complete response with PET/CT scans, bone marrow, and GI biopsies.

As knowledge on the role of genetic abnormalities continues to grow in MCL, there are limited data in many areas and it is unknown whether certain mutations, such as CARD11, will prove to be reliable targets. Other driver mutations, such as NOTCH1, NOTCH2, and c-myc have been shown to be associated with poorer outcomes. Wang highlighted that data may be gleande through programs such as the MCL Program of Excellence at MD Anderson in which patients with relapsed or refractory MCL undergo a front-door genetic panel and minimal residual disease and RNA-sequencing.

Frontline therapy for MCL is the most important therapy [as] many patients have only one opportunity [for treatment], Wang said. Each time you give a therapy the efficacy goes down [and] the interval of remission shortens until about 5 to 10 cycles, [then] the resistance becomes 100 [and] the efficacy becomes 0.

The natural history of MCL has shown that patients tend to be in remission and then relapse, with this occurring multiple times. Giving the best treatment in frontline when the patients immune resources, bone marrow, and organs are still in good condition is important. Wang noted he uses doublet therapies for those with high-risk disease because single-agent rituximab (Rituxan) is not adequate. Maintenance therapy is critical as well and other factors to keep in mind during treatment are toxicities, COVID-19 infection, and the personal history of patients including insurance, family support, and home location.

There is art in maintenance after frontline therapy. Rituximab is useful [to] prolong overall survival after almost any therapies, he said.

Although rituximab plus ibrutinib (Imbruvica) has demonstrated high response rates and can be used effectively, atrial fibrillation remains a prominent cardiac toxicity occurring in approximately 24% of patients.2 The R2 regimen of lenalidomide (Revlimid) and rituximab is an effective therapy that can be dose adjusted for renal failure. Wang noted he would also use the combination in patients with certain disease characteristics, such as tonsillar MCL or lymphoma that moves in the renal gland.

For patients with high-risk diseasea Ki67 index greater than 50%, a TP53 mutation, and/or pleomorphic/blastoid diseasetreatments include the SHINE regimen (ibrutinib, bendamustine[Bendeka]/rituximab and rituximab maintenance)3, rituximab plus ibrutinib maintenance for 2 years, acalabrutinib (Calquence)/venetoclax (Venclexta)/rituximab, or acalabrutinib plus R2. Wang said that rarely are bendamustine/rituximab and rituximab maintenance used or RCHOP plus rituximab.

MD Anderson is also evaluating rituximab plus acalabrutinib, rituximab plus pirtobrutinib, rituximab/pirtobrutinib/venetoclax, and ibrutinib monotherapy for smoldering MCL.

Younger patients with high-risk disease can receive the Window 2 study (NCT03710772) therapy of ibrutinib, venetoclax, and rituximab followed by a risk-stratified observation or short-course R-hyper-CVAD, according to Wang. Additional therapies include rituximab plus ibutinib with or without venetoclax maintenance for 2 years, acalabrutinib/venetoclax/rituximab, or acalabrutinib plus R2.

The Window-3 trial (NCT05495464) is ongoing at MD Anderson evaluating more treatment combinations for patients in this subgroup.

Approved agents for the treatment of MCL are bortezomib, lenalidomide, ibrutinib, acalabrutinib, zanubrutinib, the CAR T-cell therapy brexucabtagene autoleucel (Tecartus), and, most recently, pirtobrutinib (Jaypirca). Targeted agents and combinations such as BTK inhibitors, brexucabtagene autoleucel, chemotherapies, and stem cell transplants are under additional investigation as well.

Additionally, low-dose radiation for patients with an ATM mutation has shown efficacy and Wang noted that only 1 to 2 cycles of radiation are needed. Forty percent of patients have a frontline ATM mutation, he said. When you have ATM mutation the tumor is exquisitely sensitive to radiationso radiation therapy is a great therapy for MCL, sometimes you dont have to use high doses.

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Wang Details Caveats to Standards of Care for Treating Patients ... - OncLive

Enrollment has commenced for a phase 2 trial (NCT05739981) investigating the DNA-based interleukin-12 (IL-12) immunotherapy IMNN-001 (formerly GEN-1) in combination with bevacizumab (Avastin) and chemotherapy in patients with advanced ovarian cancer.1

The study is expected to enroll 50 patients with stage III/IV advanced ovarian cancer, and it is being led by principal investigator Amir Jazaeri, MD, the vice chair for Clinical Research and director of the Gynecologic Cancer Immunotherapy Program in the Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center.

The medical need for new innovative therapeutic approaches in ovarian cancer is major. The majority of patients with ovarian cancer are diagnosed with stage III/IV disease and face low cure rates of 15% or less, Corinne Le Goff, PharmD, MBA, president and chief executive officer of IMUNON, stated in a news release. The amount of data this study will generate will be a huge contribution to the treatment of ovarian cancer, and we believe the combination of IMNN-001 and bevacizumab has important potential.

In our animal studies, the combination clearly showed strong synergies. We are hoping that with this study we can potentially transform the current treatment landscape and provide new hope to women suffering from this deadly cancer.

IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein.

Previously reported data from the phase 1 OVATION 1 trial (NCT02480374) showed that the combination of IMNN-001 plus chemotherapy demonstrated activity and safety in patients with advanced epithelial ovarian cancer. Among 14 enrolled patients, 12 (85.7%) experienced a radiological response, including 2 complete responses and 10 partial responses.2

The most common treatment-emergent adverse effects that were at least possibly related to treatment included nausea, fatigue, abdominal pain/cramping, anorexia, diarrhea, and vomiting. Grade 4 neutropenia occurred in 8 patients, and this was attributed to neoadjuvant chemotherapy. No dose-limiting toxicities were reported.

The phase 2 trial is enrolling patients with a suspected diagnosis of high grade epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with histologic confirmation per pre-treatment biopsies.3 Patients are also required to have an International Federation of Gynecology and Obstetrics stage of III or IV that has been determined to benefit from neoadjuvant therapy.

Other key inclusion criteria include the discontinuation of any hormonal therapy directed at the tumor within at least a week prior to first study treatment, an ECOG performance status of 0 or 1, and adequate bone marrow, renal, hepatic, and neurologic function.

The trial is excluding patients who have received prior treatment with IMNN-001; have had treatment with corticosteroids within 2 weeks of study entry or have a clinical requirement for ongoing systemic immunosuppressive therapy; have autoimmune disease requiring immunosuppressive therapy within the past 2 years; or have received prior radiotherapy or chemotherapy to any portion of the abdominal cavity or pelvis.

Enrolled patients are being randomly assigned 1:1 to receive chemotherapy plus bevacizumab with or without IMNN-001. Chemotherapy will consist of 175 mg/m2 of paclitaxel followed by area under the curve 5/6 of carboplatin on day 1 of each 21-day cycle. Neoadjuvant chemotherapy will consist of 4 to 6 cycles per investigators discretion, and adjuvant chemotherapy will last for another 3 cycles.

Bevacizumab will be administered at 15 mg/kg on day 1 of cycles 2, 3, 6, and 7, and bevacizumab will also be given as a single agent every 3 weeks during the maintenance phase for up to 18 cycles, or until disease progression or unacceptable toxicity. In total, bevacizumab will be given in up to 22 cycles.

Patients in the experimental arm will be given 80 mg/m2 of IMNN-001 once per week on day 15 of cycle 1 and continued through the end of adjuvant therapy. Following the conclusion of chemotherapy, IMNN-001 will be administered every 21 days with bevacizumab in patients who are BRCA negative and homologous recombination proficient.

The primary end point of the study is reducing the minimal residual diseasepositivity rate at second look laparoscopy from an expected 70% in the control group to 35% in the experimental group. Secondary end points include progression-free survival and overall survival.

Break Through Cancer is excited to support this important study, Tyler Jacks, PhD, president of Break Through Cancer, founding director of MITs Koch Institute for Integrative Cancer Research, and the David H. Koch Professor of Biology, stated in a news release.1 Our foundation has brought together some of the nations top cancer research centers to collaborate, accelerate research and clinical trials, and ultimately intercept and find cures for the deadliest cancers.

The phase 1/2 OVATION 2 trial (NCT03393884) is also evaluating IMNN-001 plus paclitaxel/carboplatin vs chemotherapy alone.4

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Enrollment Begins for Phase 2 Trial of IMNN-001 Plus Bevacizumab ... - OncLive