CAR T-cell therapies continue to elicit encouraging responses with manageable toxicity in older patients with lymphomas who may be unable to tolerate more intensive approaches, according to Pashna N. Munshi, MD.
In July 2020, the FDA approved brexucabtagene autoleucel (Tecartus; formerly KTE-X19)for the treatment of adult patients with relapsed/refractory mantle cell lymphoma (MCL) based on data from the ZUMA-2 trial. In 60 patients evaluable for efficacy based on a minimum duration of follow-up for response of 6 months, results showed that a single infusion of the product resulted in an 87% objective response rate (ORR), with a 62% complete remission (CR) rate.1
Brexucabtagene autoleucel is going to provide patients with MCL with another treatment option. MCL is a very heterogeneous disorder; it can behave indolently in some patients, but in others, it's a very aggressive disease, said Munshi, associate clinical director of the Stem Cell Transplant and Cellular Immunotherapy Program at MedStar Georgetown University Hospital. Patients who relapse early often don't do very well and cannot get into remission. Having an option like CAR T-cell therapy gives these patients a chance to receive [a treatment] that is targeted, with manageable toxicities.
The ZUMA-5 trial with axicabtagene ciloleucel (axi-cel; Yescarta) showed similarly impressive response rates, according to Munshi. Results from an interim analysis revealed that at a median follow-up of 15.3 months, patients with follicular lymphoma and marginal zone lymphoma (MZL) who received treatment with the CAR T-cell product experienced an ORR of 93% and a CR rate of 80%.2
In an interview withOncLive during the 2020 Institutional Perspectives in Cancer webinar on Leukemia/Lymphoma, Munshi, who is also an assistant professor of medicine at Georgetown University, discussed the CAR T-cell therapies that have emerged in the lymphoma space and highlighted the next steps for research with these products.
OncLive: Could you highlight some of the CAR T-cell products that are generating excitement in lymphoma?
Munshi: The most recently approved therapy was brexucabtagene autoleucel, which was evaluated in the ZUMA-2 trial; this was a phase 2, single-arm, open-label, multicenter trial done in patients with relapsed/refractory MCL. This product is similar to the CD19-targeted CAR T-cell product axicabtagene ciloleucel, although some differences exist.[Results showed] an ORR of 93%, with CR rates of 67% in a total of 68 patients. The ORR and the durability of those responses resulted in the approval of the product.
Another important clinical trial that is currently underway is ZUMA-5, which is being done in patients with relapsed/refractory indolent non-Hodgkin lymphoma. This trial had 2 cohorts: patients with follicular lymphoma and those with MZL. The follicular lymphoma cohort is now closed to enrollment and the results were [presented during] the 2020 ASCO Virtual Scientific Program and those results will be presented at the 2020 ASH Annual Meeting.
Ninety-six patients were evaluable for efficacy. [The ORR] was 95% in the follicular lymphoma arm and 81% for the MZL arm. At the time of data cutoff, 68% of patients had ongoing responses, so this is a very exciting therapy. We hope this will be a new indication for the treatment of patients with relapsed/refractory indolent lymphoma, especially follicular lymphoma.
What is the clinical significance of the brexucabtagene autoleucel approval?
One type of treatment approach that patients with MCL are offered is a high-dose chemotherapy with autologous stem cell transplantation. However, many patients may not be eligible for such high-intensity chemotherapy. Patients may be older, frail, and not in good enough shape to receive high-intensity treatment. CAR T-cell therapy may be given to these patients.
[In the ZUMA-2] trial, there was a substantial number of older patients [who achieved] very good responses [with the therapy]. The ORR was 87% at a median follow-up of about 8.6 months; this was later updated because 4 patients in the initial study were deemed as nonresponders by an independent radiology review. This therapy can potentially be given more up front for patients with MCL who have progressed on 2 or more lines of therapy.
Many older patients were also included on the ZUMA-5 trial. Could you expand on this? What does the safety look like with this product?
The median age range of participants was vast; the trial included patients who were as young as 34 years up to those who were 79 years. Many of these patients were older; they were over 60 years and yet, they could tolerate this therapy with really impressive ORRs.
Even though these therapies do have toxicities, such as cytokine release syndrome (CRS) and neurological effects, they are well [managed] by experts. We use therapies, such as the IL-6 inhibitor tocilizumab(Actemra) up front to treat CRS, as well as up-front steroids, in patients who may have some level of neurological involvement. In terms of the ZUMA-5 trial, it is important to note the age range and the fact that at least 73% of these patients were refractory to the last therapy they had received.
What are some of the updates that have been reported with tisagenlecleucel (tisa-cel; Kymriah)?
The [manufacturers of] tisa-cel presented real-world data with their commercial product and compared it with clinical trial results. They saw, if not similar, an almost improved toxicity profile and similar response rates which were reflective of their clinical trial.
Based on the initial JULIET study, 92% of patients were allowed bridging therapy. Only 72% to 75% of patientsreceived bridging therapy on the commercial side. The real-world data showed a median ORR of approximately 60%, with approximately 40% achieving a CR; [this] is similar to the 40% best responses observed on the clinical trial.
The grade 3 or higher toxicities were very low; only 4.3% of patients experienced CRS; that is remarkable. More patients are increasingly being given up-front tocilizumab or steroid use, which is mitigating the toxicity of these therapies and making it safer for patients.
What are the next steps for research with this modality?
A Pandora's box has been opened. Were not limited to CAR T-cell therapies; many, many targets are now being explored. There are CAR natural killer cell therapies; there are specific targets in leukemia that are being studied. CD33-targeted CAR T-cell trials are being done, and investigators are also exploring a combination of CD33-targeted and CD123-targeted products.
[Additionally], there are bispecific CAR T-cell engagers. Different methods are being used to try to see why relapse happens with CAR T-cell therapy. Maybe 1 antigen is lost and, therefore, you need a second antigen to be targeted, [hence] the CD19/CD22 combinations being examined in acute lymphoblastic leukemia. Many different forms of therapies are under exploration.
The next step is to find a way to [minimize] toxicities and relapse in the CAR T-cell world.The final stage is to look at off-the-shelf or allogeneic CAR T products. With these options, patients may not have to wait for their own cells to be processed as CAR T cells; the product will be readily available. That will really change how quickly these patients receive treatment, and it also potentially shifts the bar for many diseases.
For example, if this [approach] is successful in acute myeloid leukemia, many patients may get this therapy when they were not otherwise eligible for allogeneic stem cell therapy. If this therapy were to put them in remission, they could potentially make it to an allogeneic stem cell transplant or may not even need to undergo a transplant if these therapies prove durable. It's a very exciting future for CAR T cells.
What is your take-home message to your colleagues?
What I'd like to tell all the providers out there who are seeing patients with lymphoma and myeloma, especially with regard to refractory lymphomas, early referral is key. This is an autologous product, so it can take anywhere from 2 weeks to 3 weeks [to manufacture], depending on the type of product. When patients have an active malignancy, they're really waiting with active disease and it's hard to treat them with new therapy in between while they wait to receive CAR T-cells.
There is an aspect of overcoming insurance hurdles with some of these patients, as these are expensive products. Many milestones need to be achieved before patients can [receive] these therapies. Family members need education about the care that patients need once they're sent home. Also, referring providers may need to see these patients more frequently after they're treated with CAR T-cells, depending on their need.
There is some education that goes into this and we are armed as specialized, authorized treatment centers to arm patients and their caregivers with the knowledge about these therapies, the adverse effects of these approaches, and potentially provide them with a therapy that would make a change to the cancer in their body.
Read more:
CAR T-Cell Therapies Continue to Raise the Bar in Lymphoma Management - OncLive
- Biology of stem cells: an overview - PMC - National Center for ... - March 26th, 2024
- Iron Limitation Preserves Youthfulness of Blood Stem Cells - Mirage News - March 13th, 2024
- Mini organs grown from stem cells of unborn babies for the first time in breakthrough - The Mirror - March 9th, 2024
- The Effect of Short-Term NAD3 Supplementation on Circulating Adult Stem Cells in Healthy Individuals Aged 40-70 ... - Cureus - March 7th, 2024
- University of Liverpool Spin-Out Emerges, Pioneering Novel Adult Stem Cell-Based Therapies - India Education Diary - March 7th, 2024
- Scientists have used cells from fluid drawn during pregnancy to grow mini lungs and other organs - Yahoo News Canada - March 6th, 2024
- Japan approves new stem cell-based Alzheimer's therapy By Proactive Investors - Investing.com Australia - January 20th, 2024
- Cyberstalking pits Harvard professor against PubPeer Retraction ... - Retraction Watch - December 5th, 2023
- 10 functional health predictions for 2024, according to a doctor and ... - 1330 WFIN - December 5th, 2023
- See the Brain Like Never Before in This Gorgeous Art - Scientific American - December 5th, 2023
- Geron Announces Publication in The Lancet of Results from the ... - BioSpace - December 5th, 2023
- Stem cell injections could be the key to curing MS - Freethink - December 3rd, 2023
- Jaypirca (pirtobrutinib) Now Approved by U.S. FDA for the ... - Investors | Eli Lilly and Company - December 3rd, 2023
- Comparative Efficacy and Safety of Four JAK Inhibitors for ... - HealthDay - December 3rd, 2023
- City lights up for Francis on Anthony Nolan's birthday - Liverpool Express - December 3rd, 2023
- NOT-AR-23-022: Request for Information on Themes for the NIAMS ... - National Institutes of Health (.gov) - December 3rd, 2023
- December 2023: Intramural Papers of the Month - Environmental Factor Newsletter - December 1st, 2023
- CNA Explains: What is cord blood banking and why do parents do it? - CNA - December 1st, 2023
- Regulation of myogenesis and adipogenesis by the electromagnetic ... - Nature.com - December 1st, 2023
- The effects of vitamin K on bone health - News-Medical.Net - December 1st, 2023
- Dr Hurwitz on Ongoing Investigations of the Use of CAR T-Cell ... - OncLive - December 1st, 2023
- Mitophagy in human health, ageing and disease - Nature.com - December 1st, 2023
- Adult Stem Cells - Stem Cells and the Future of Regenerative Medicine ... - November 29th, 2023
- Navigating The Regulatory Landscape Of Longevity Health Products ... - Mondaq News Alerts - November 29th, 2023
- MS breakthrough could lead to treatments that halt disease's ... - inews - November 29th, 2023
- Reprogramming tissue mechanically to promote wound healing - Phys.org - November 29th, 2023
- Latest Advances in Arthritis Diagnosis and Treatment at American ... - HealthDay - November 29th, 2023
- Sex-associated differences in frequencies and prognostic impact of ... - Nature.com - November 29th, 2023
- Hematologists Dive into the Current Treatment Landscape - OncLive - November 29th, 2023
- Team discovers protein crucial for B cell differentiation and antibodies - Phys.org - November 29th, 2023
- Science Talk - I survived cancer as a child and now I'm working to ... - The Institute of Cancer Research - November 29th, 2023
- First Edition: Nov. 29, 2023 - KFF Health News - November 29th, 2023
- Symptoms: Unilateral Hearing Loss and Tinnitus : The Hearing Journal - LWW Journals - November 29th, 2023
- Mitigation of sepsis-induced acute lung injury by BMSCs | IJN - Dove Medical Press - November 29th, 2023
- A Case of a Constricted Vessel: The Impact of Acute Myeloid ... - Cureus - November 29th, 2023
- Mum brushed off fatigue after having baby but fall sparked deadly diagnosis - The Mirror - November 29th, 2023
- How heritable is the epigenome? - Drug Discovery News - November 29th, 2023
- The Blueprint of Regeneration: Scientists Discover How to Turn Stem Cells Fate - Revyuh - November 27th, 2023
- BrainStorm Cell Therapeutics Announces In-Person Meeting with ... - Marketscreener.com - November 27th, 2023
- Stem Cell Therapy Developed in Korea Begins Treatment for ... - PharmiWeb.com - November 25th, 2023
- COVID-19 Pandemic's Adverse Effect on Bone Health in Young ... - HealthDay - November 25th, 2023
- Sickle cell breakthrough - The Indian Express - November 25th, 2023
- Wall thickness analysis method for judging the degree of lower ... - Nature.com - November 25th, 2023
- Century Therapeutics to Present at the Piper Sandler 35th Annual Healthcare Conference - Yahoo Finance - November 23rd, 2023
- Disease Transmission and Diagnosis of Zika Virus - Cureus - November 23rd, 2023
- Gene-editing therapy for sickle cell earns conditional approval in UK - Sickle Cell Disease News - November 23rd, 2023
- Stem Cell Therapy Developed in Korea Begins Treatment for ... - Newswire - November 21st, 2023
- Efficacy of ADSC-CM in Patients with Telogen Effluvium | SCCAA - Dove Medical Press - November 21st, 2023
- BrainStorm Cell Therapeutics Announces In-Person Meeting with ... - PR Newswire - November 21st, 2023
- The Impact of CAR T Cell Therapy on Managing R/R LBCL - OncLive - November 21st, 2023
- Mansour bin Zayed witnesses inauguration of ADSCC Bone Marrow Transplant & Cellular Therapy Congress 2023 - ZAWYA - November 21st, 2023
- Listeria: Who is most susceptible? What are the Symptoms? What ... - Food Poison Journal - November 21st, 2023
- Scope Of Issued Patents May Be Limited By Prosecution Estoppel ... - Mondaq News Alerts - November 21st, 2023
- Qrons Announces the Addition of Professor Shiri Navon-Venezia to ... - StreetInsider.com - November 21st, 2023
- Financially strapped Athersys raises $10.4M - cleveland.com - November 19th, 2023
- From the India Today archives (2010) | How stem cells can save your life - India Today - November 19th, 2023
- Inactivation of the tumor suppressor gene Apc synergizes with H ... - Science - November 19th, 2023
- The Origins of Multiple Myeloma and Why it Matters - HealthTree For AML - Acute Myeloid Leukemia - November 19th, 2023
- Treatment Considerations With TROP2-Targeted Therapy - OncLive - November 19th, 2023
- Athersys narrows loss, raises $10.4 million during third quarter to ... - The Business Journals - November 17th, 2023
- Who was Dolly the Sheep and what happened to her? The story of ... - BBC Countryfile Magazine - November 17th, 2023
- UK first to approve CRISPR treatment for diseases: what you need to ... - Nature.com - November 17th, 2023
- 1st sickle cell patient to be given therapy restoring fetal hemoglobin - Sickle Cell Disease News - November 15th, 2023
- Century Therapeutics Reports Third Quarter 2023 Financial Results and Provides Business Updates - Century - Benzinga - November 13th, 2023
- Century Therapeutics Appoints Brent Pfeiffenberger, Pharm.D., MBA, as Chief Executive Officer - Yahoo Finance - November 11th, 2023
- Century Therapeutics and FUJIFILM Cellular Dynamics Announce Licenses for the Development and Commercialization of iPSC-Derived Cell Therapies in... - November 11th, 2023
- AAO 2023: Paul Runge and his ROP treatments in the Ukraine - Modern Retina - November 11th, 2023
- The Evolutionary Reasons We Are Drawn To Horror Movies and ... - Slashdot - November 11th, 2023
- Century Therapeutics Reports Third Quarter 2023 Financial Results ... - GlobeNewswire - November 11th, 2023
- Century Therapeutics Reports Third Quarter 2023 Financial Results ... - StreetInsider.com - November 9th, 2023
- NYU Langone Health Performs World's First Whole-Eye & Partial ... - NYU Langone Health - November 9th, 2023
- BrainStorm to Announce Third Quarter 2023 Financial Results and ... - BioSpace - November 9th, 2023
- Can we cut cost and pain of IVF? Start-up CEO tries out own ... - Genetic Literacy Project - November 9th, 2023
- Jasper Therapeutics Reports Third Quarter 2023 Financial Results ... - BioSpace - November 9th, 2023
- Impaired neural stress resistance and loss of REST in bipolar ... - Nature.com - November 9th, 2023
- Functional genomics and systems biology in human neuroscience - Nature.com - November 9th, 2023
- Trial launched to test CAR T-cell therapy in dogs diagnosed with ... - EurekAlert - November 9th, 2023
- The-Gut's-Lasting-Impact-on-Severe-COVID-19-Immune-Response - Infectious Disease Special Edition - November 9th, 2023
- Emerging Cure for Sickle Cell on its Way to FDA Approval, Carries ... - Dallasweekly - November 7th, 2023
- The science works, but will we pay for it? - Irish Medical Times - November 7th, 2023
Recent Comments