In a recent OncView discussion, Connie Lee Batlevi, MD, PhD, a medical oncologist focused on the treatment of Hodgkin and non-Hodgkin lymphomas at Memorial Sloan Kettering Cancer Center in New York, shared clinical experiences and perspectives regarding treatments in the follicular lymphoma space.
To begin the discussion, Batlevi said the risk of disease relapse in this population is high, and it is increasing as patients are living longer. Follicular lymphoma is considered a noncurable indolent lymphoma, she explained. The goal of any treatment is to balance effectiveness of treatment, quality of life, and cost of care. In some longitudinal studies, about 50% of patients relapse after frontline therapy [with] more than a decade of observation. However, as patients are thankfully living beyond a decade, we know that patients are ultimately always at risk for a relapse.
Batlevi detailed her rationale for therapy selection at each relapse and considerations for sequencing agents in this patient population.
According to Batlevi, factors that may play into treatment selection at first relapse include a patients functional status, characteristics of their disease at relapse, disease volume on imaging, laboratory findings, metabolic activity on PET scan, and genetic and pathologic assessments.
A biopsy is almost always an important aspect of disease assessment because it is key to identifying a transformation. If a transformation were to occur, where the follicular lymphoma changes to a diffuse large B-cell lymphoma, that would change the management, said Batlevi. Treatment selection also hinges on other factors, such as what therapy was used in the frontline setting.
In addition, certain treatments have backbones that may be too harsh for frail patients, such as bendamustine or the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone. Immune-based targeted therapies like lenalidomide (Revlimid) may not be optimal for patients whose lifestyles are not compatible with a rigorous administration schedule.
Some patients in first relapse, Batlevi noted, may in fact be better suited for observation. Clinical guidelines help determine who may be appropriate for this approach.
Batlevi said she likes to refer to the guidelines of the Groupe dEtude des Lymphomes Folliculaires, a set of clinical criteria that were validated to guide frontline treatment of follicular lymphoma. Those criteria include having more than 3 lymph nodes that each measuremore than 3 cm or any 1 lymph node measuring more than 7 cm, plus other organ and laboratory measures for determining if immediate therapy is required.1
In a patient who is receiving therapy in the third-line setting or beyond, Batlevi again stressed the importance of understanding that patients needs based on their lifestyle and life expectancy. Caring for these patients can be gratifying, she said, as she comes to understand their needs and is able to tailor an individualized treatment approach.
Therapy Options For Third-line and Beyond Disease
In the third line, clinicians may choose from several options, both with chemotherapy and without. Classically, any chemotherapy remains an option, although its not likely going to be at the forefront of our resources. There are [also] autologous stem cell transplants, which use really high doses of chemotherapy, Batlevi said. The nonchemotherapy options fall into various classes, such as PI3K inhibitors, EZH2 inhibitors, immune-based therapies like chimeric antigen receptor T cells, and also allogeneic stem cell transplant, which is essentially an immune replacement therapy to control follicular lymphoma.
Molecular testing is particularly useful for therapy selection for patients with this disease. For example, patients with EZH2-positive relapsed or refractory follicular lymphoma following 2 prior therapies may receive treatment with the recently approved agent tazemetostat (Tazverik).2 Tazemetostat also may be used in other patients with follicular lymphoma who have no other satisfactoryalternative treatment options.
EZH2 is very important for B-cell development, [and it is mutated] in about 15% to 25% of follicular lymphomas, said Batlevi. In the phase 2 clinical trial that led to [tazemetostats] approval [Study E7438-G000-101; NCT01897571]overall response rate was about [69% in patients with the mutations] and in wild type, it was about 35%.3 Notably, the overall disease control rate in the EZH2-mutant group was 98%, composed of 13% complete responses (CRs), 56% partial responses, and stable disease in 29%.
According to Batlevi, other benefits of tazemetostat include its tolerable safety profile. Fewer than 10% of patients require dose reductions due to treatment-emergent adverse effects (AEs) and fewer than 5% have to discontinue therapy for treatment-related causes.
Tazemetostat is a very easy-to-give drug. Its taken twice a day by mouth. There are no substantial neutropenias or leukopenias that are concerning, [which is] especially [important given the COVID-19] pandemic, said Batlevi. In terms of real-world use, patients with EZH2 mutations and frail patients with mutations are the most likely to receive benefit from this treatment compared with other available agents.
Turning to PI3K inhibitors, Batlevi described the 4 that are available to treat patients in the third-line setting and beyond: idelalisib (Zydelig), duvelisib (Copiktra), copanlisib (Aliqopa), and umbralisib (Ukoniq).
Each target is [for a] slightly different PI3K isoform. For example, idelalisib targets g and d and umbralisib is a d and CK1-e targeter. In general, responses are in the 50% range and CR [rates] are typically less than 10%.
Other considerations of treatment with PI3K inhibitors are their AE profiles. Both idelalisib and duvelisib have known risks of colitis and pneumonitis, whereas copanlisib, although generally more tolerable than the other 2, can result in hyperglycemia and hypertension.
The fourth, umbralisib, is newly approved for use in patients with relapsed or refractory marginal zone lymphoma, following at least 1 prior anti-CD20targeting regimen, and in patients with follicular lymphoma who have had 3 prior lines of therapy.4 Overall, fewer patients are on it so far, so we just need to see how it evolves, Batlevi said.
With the approval of the first EZH2 inhibitor in follicular lymphoma, Batlevi expects the trend toward targeted agents in this space to continue. It will open new doors in terms of [patients] in whom we can use genetic profiling, [consequently] personalizing medicine to develop more treatments in lymphoma, she noted.
Additionally, Batlevi expects to see more ongoing trials examining combination treatments with these newer agents, and that more indications will become availablefor treating frontline disease.
1. Brice P, Bastion Y, Lepage E, et al. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe dEtude des Lymphomes Folliculaires. Groupe dEtude des Lymphomes de lAdulte.J Clin Oncol. 1997;15(3):1110-1117. doi:10.1200/JCO.1997.15.3.1110
2. FDA granted accelerated approval to tazemetostat for follicular lymphoma. FDA. June 18, 2020. Accessed September 7, 2021. https://bit.ly/3ngfQch
3. Morschhauser F, Tilly H, Chaidos A, et al. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial.Lancet Oncol. 2020;21(11):1433-1442. doi:10.1016/S1470-2045(20)30441-1
4. FDA grants accelerated approval to umbralisib for marginal zone lymphoma and follicular lymphoma. FDA. February 5, 2021. Accessed September 10, 2021. https://bit.ly/3k2EcnQ
Editors Note: Interview quotes slightly modified for readability.
See more here:
Updates in Therapies of Relapsed and Refractory Follicular Lymphoma - Cancer Network
- SUM Hospital conducts Odishas first stem cell transplantation - The Times of India - April 24th, 2024
- Cancer treatment: What is stem cell therapy, and how does it work? - Moneycontrol - April 24th, 2024
- The murky, unregulated world of anti-ageing stem cell therapy - The Telegraph - April 24th, 2024
- Drug Prototype Promising in Treatment of Pulmonary Disease - Medscape - April 20th, 2024
- Man Paralyzed In Surfing Accident Regains Ability to Walk After Stem Cell Treatment - The Inertia - April 20th, 2024
- Medical breakthrough: 8-year-old boy first in New York to receive FDA-approved gene therapy for rare inherited blood disorder - WABC-TV - April 20th, 2024
- Stem Cell Treatment Helped A Man Who Was Paralyzed From The Neck Down To Stand On His Own - Bored Panda - April 20th, 2024
- UM, CUHK jointly hold symposium on stem cells and regenerative medicine - gcs.gov.mo - April 20th, 2024
- Paralysed patient now able to walk as stem cell therapy shows promising results - WION - April 15th, 2024
- Andrew Steele Sees Aging as the Root of Disease - Worth - Worth Magazine - April 15th, 2024
- The astonishing effect of stem cell implants - as groundbreaking treatment 'transforms' life for those with brain damage ... - Daily Mail - April 15th, 2024
- Consumer Alert on Regenerative Medicine Products Including Stem Cells - FDA.gov - April 13th, 2024
- This Startup Wants To Be OpenAI Of Stem Cell Therapy, Targets $250B Market - Forbes - April 13th, 2024
- Brain-cell transplants are the newest experimental epilepsy treatment - MIT Technology Review - April 3rd, 2024
- Global Regenerative Medicine Market to Touch Valuation of USD 472.95 Billion by 2032, at 25.86% CAGR: Astute ... - Yahoo Finance - April 1st, 2024
- Explosive Growth Projected for Stem Cell Market, Expected to Surpass $37 Billion by 2030 As Revealed In New... - WhaTech - April 1st, 2024
- Integrating New Therapies With Autologous Stem Cell Transplant in Myeloma - Targeted Oncology - April 1st, 2024
- New tool provides researchers with improved understanding of stem cell aging in the brain - Medical Xpress - March 30th, 2024
- The ISSCR announces 2024 election results - EurekAlert - March 28th, 2024
- Exosomes and Stem Cells Are the Future of Anti-Aging - NewBeauty Magazine - March 28th, 2024
- Charles River Extends Gene Therapy Alliance with NUS Medicine - Contract Pharma - March 22nd, 2024
- Exciting opportunities in stem cell technology and regenerative biology in Indian healthcare industry - Express Healthcare - March 22nd, 2024
- Charles River Announces Extension of Gene Therapy Manufacturing Alliance with NUS Yong Loo Lin School of Medicine - Yahoo Finance - March 22nd, 2024
- Opinion: The revolutionary sickle cell therapies - MSN - March 22nd, 2024
- 10 Years of Kansas Regenerative Medicine Center - KSAL - March 22nd, 2024
- BioCardia and StemCardia Announce Biotherapeutic Delivery Partnership - Diagnostic and Interventional Cardiology - March 17th, 2024
- Cynata Therapeutics' breakthrough in regenerative medicine - Finance News Network - March 17th, 2024
- New Positive Data Presented on Briquilimab Conditioning in Patients with Fanconi Anemia - GlobeNewswire - March 17th, 2024
- Novel 3D stem cell therapy to treat critical limb ischaemia - Drug Target Review - March 15th, 2024
- Breaking Boundaries: Pharmicell's Bold Vision for Healthcare Transformation and Monumental Growth - The Worldfolio - March 15th, 2024
- CuSTOM Organoid Research Evolving From Tool to Treatment - Research Horizons - Research Horizons - March 15th, 2024
- BioCardia and StemCardia Announce Partnership to Deliver Cell-Gene Therapy for Remuscularization of Heart - Cath Lab Digest - March 15th, 2024
- Calidi Biotherapeutics and City of Hope Announce Funding from the California Institute for Regenerative Medicine ... - Business Wire - March 13th, 2024
- Iron restriction keeps blood stem cells young, researchers find - Phys.org - March 13th, 2024
- Vitamin A could have a key role in both stem cell biology and wound healing: Study - Medical Dialogues - March 9th, 2024
- Trends in Stem Cell Transplantation Refusal for Myeloma Treatment - Targeted Oncology - March 7th, 2024
- Stem Cell Therapy Market (CAGR) of 31.1%, Future of Market Size Emerging Technologies and their Impact on ... - Taiwan News - March 7th, 2024
- This Swedish startup wants to reduce the cost, and controversy, around stem cell production - TechCrunch - March 6th, 2024
- Advancing stem cell therapy: The regulatory process to get to clinical trials - The Economic Times - March 6th, 2024
- Transitioning from traditional surgical methods to the innovative use of stem cells - pharmaphorum - March 6th, 2024
- 'Mini organs' are grown from human stem cells taken during the late stages of pregnancy for the first time - m - Daily Mail - March 6th, 2024
- Stem cell transplant cures man of HIV and leukemia, one of five to achieve full remission - Fox 28 - March 3rd, 2024
- Stem Cell Therapy Market to Boost USD 137.5 Billion by 2034 and Projected to grow at 32.10% CAGR with increasing ... - Yahoo Finance - March 1st, 2024
- Studies expand use of stem cell therapies - WPLG Local 10 - March 1st, 2024
- Innovative therapy targets and destroys leukemia stem cells - News-Medical.Net - February 27th, 2024
- Unlocking the Potential of Stem Cells: The Medical Revolution of the Century - EIN News - February 27th, 2024
- Pelage Pharmaceuticals Announces $16.75M Series A Financing led by GV to Revolutionize Regenerative Medicine ... - Yahoo Finance - February 27th, 2024
- Say Her Name - Henrietta Lacks, The Real Mother Of Stem - Her Campus - February 27th, 2024
- California Man Free of HIV And Cancer in Astonishing Medical Recovery - ScienceAlert - February 25th, 2024
- $93 million for research into improved health for children, young people and the aged, medical devices, mental health ... - Department of Health - February 25th, 2024
- Stem Cells in Regenerative Medicine - PMC - National Center for ... - February 24th, 2024
- The Promise and Reality of Stem Cell Therapy: What You Need to Know - Corporate Wellness Magazine - February 22nd, 2024
- Stem Cell Therapy: A Beacon of Hope for Patients with Untreatable Conditions - Corporate Wellness Magazine - February 22nd, 2024
- Leading Experts in Stem Cell Therapy: A Global Overview - Corporate Wellness Magazine - February 22nd, 2024
- Can Stem Cells Help Reverse the Effects of Aging? - Corporate Wellness Magazine - February 22nd, 2024
- Stem Cell Therapy for Cancer: Hope on the Horizon? - Corporate Wellness Magazine - February 22nd, 2024
- Stem Cells and Autism: A Closer Look at Innovative Treatments - Corporate Wellness Magazine - February 22nd, 2024
- Regrowth and Restoration: The Science Behind Stem Cell Therapy for Hair - Corporate Wellness Magazine - February 22nd, 2024
- Brain Recovery: The Role of Stem Cells in Stroke and Cerebral Palsy Treatments - Corporate Wellness Magazine - February 22nd, 2024
- Turning Back the Clock: The Science of Stem Cells in Anti-Aging - Corporate Wellness Magazine - February 22nd, 2024
- Insights into cellular therapies for cancer treatment - Drug Target Review - February 22nd, 2024
- The Role of Stem Cells in Rheumatoid Arthritis Recovery - Corporate Wellness Magazine - February 22nd, 2024
- Dr Ernesto Romeros vision transforms immunotherapy regenerative medicine into a global leader in stem cell treatment - Khaleej Times - February 22nd, 2024
- World-Renowned Doctors Leading the Way in Stem Cell Research and Treatment - Medical Tourism Magazine - February 20th, 2024
- Choosing the Best: A Guide to America's Premier Stem Cell Therapy Providers - Medical Tourism Magazine - February 20th, 2024
- Navigating Through the Possibilities of Stem Cell Treatment for Eye Disorders - Medical Tourism Magazine - February 20th, 2024
- Global Leaders in Stem Cell Therapy: Where Excellence Meets Innovation - Medical Tourism Magazine - February 20th, 2024
- Excellence in Stem Cell Treatment: How the US is Pioneering Global Healthcare Solutions - Medical Tourism Magazine - February 20th, 2024
- Clarifying Memory Loss Treatments: The Role of Stem Cells - Medical Tourism Magazine - February 20th, 2024
- Battling Inflammation: Stem Cell Therapy for Rheumatoid Arthritis - Medical Tourism Magazine - February 20th, 2024
- Digestive Health and Stem Cells: Treating Ulcerative Colitis and Crohn's Disease - Medical Tourism Magazine - February 20th, 2024
- Top Stem Cell Clinics in the USA: Pioneering Treatments for Chronic Conditions - Medical Tourism Magazine - February 20th, 2024
- Stem Cells and Autism: Understanding the Potential for Innovative Treatments - Medical Tourism Magazine - February 20th, 2024
- Stopping the awakening of sleeping Acute Myeloid Leukaemia stem cells to prevent disease relapse - University of Birmingham - February 20th, 2024
- City of Hope Achieves Ground Breaking Treatment for Blood Cancer and HIV - Medriva - February 18th, 2024
- Regenerative Medicine Market Size to Worth USD 95 Billion by 2032 - InvestorsObserver - February 18th, 2024
- North America Organoids Market Projected to Reach US$ 5.35 Billion by 2030, Riding on a CAGR of 21.5% - GlobeNewswire - February 18th, 2024
- Chinese team tests lung treatment that may be first to reverse COPD damage - South China Morning Post - February 15th, 2024
- Why leukemic stem cells not harmed by chemotherapy begin to grow and produce AML cells after treatment - Medical Xpress - February 15th, 2024
- Regenerative Medicine Market is Expected to Reach $49.0 Billion | MarketsandMarkets - Yahoo Finance - February 15th, 2024
Recent Comments