Combination therapy with ponatinib (Iclusig) and blinatumomab (Blincyto) induced a complete response in all patients with Philadelphia chromosome (Ph)positive acute lymphocytic leukemia (ALL) who were treated on a phase 2 study (NCT03263572), according to a presentation at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.1
The chemotherapy-free, hematopoietic stem cell transplant (HSCT)sparing regimen for patients receiving systemic therapy in the first-line (n = 20) led to a complete response (CR) rate or pathologic CR rate of 100%, while patients with relapsed/refractory Phpositive ALL had a rate of 89%. Moreover, patients in the frontline Phpositive cohort had a major molecular response (MMR) of 100% and a complete molecular response (CMR) of 85%.
The combination of ponatinib and blinatumomab is safe and effective in Ph-positive ALL, Nicholas James Short, MD, an assistant professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, said during an oral presentation of the data. Overall, the novel chemotherapy-free combination of ponatinib and blinatumomab appears to be a promising regimen in both frontline and relapsed/refractory Ph-ALL, as well as in chronic myeloid leukemia in lymphoid blast phase [CML-LBP]. Given the particularly favorable outcomes of newly diagnosed patients with frontline, Ph-positive ALL who were not transplanted in first remission, these data suggest that this regimen may serve as an effective transplant-sparing regimen in this population.
Chemotherapy plus a TKI has become the standard of care in newly diagnosed Ph-positive ALL, with first- and second-generation TKIs yielding 5-year overall survival (OS) rates of approximately 35% to 50%.2-4 Moreover, while ponatinib has yielded promising activity in patients with T315I mutations, which are present in up to 75% of patients at relapse,5 blinatumomab has demonstrated efficacy as a monotherapy in the relapsed/refractory setting, and in combination with dasatinib in newly diagnosed patients.6,7
The trial enrolled patients with newly diagnosed or relapsed/refractory Ph-positive ALL, as well as lymphoid accelerated or blast phase CML. Patients who had previously received 1 to 2 courses of chemotherapy with or without a TKI were able to enroll in the newly diagnosed cohort. Additionally, patients needed to be over 18 years of age, with a ECOG performance status of 0-1, and adequate hepatic function in order to enroll.
Patients with uncontrolled or active cardiovascular disease, including a history of myocardial infarction, cardiovascular accident, or revascularization within 3 months; congestive heart failure with reduced left ventricular ejection fraction; atrial of ventricular arrhythmia; a history of arterial or venous thromboembolism; or uncontrolled hypertension were not able to enroll on the study. Additional exclusion criteria included significant central nervous system (CNS) pathology with the exception of CNS leukemia.
Patients received a 30 mg induction dose of ponatinib and a standard dose of blinatumomab on a 4 weeks on, 2 weeks off schedule. From there, patients received up to 4 consolidation cycles of the regimen followed by maintenance ponatinib for 5 years, the dose of which decreased to 15 mg daily once patients achieved a CMR. All patients were given 12 doses of intrathecal chemotherapy with an altering administration of cytarabine and methotrexate.
The primary of end point of the trial was CMR rate in the frontline cohort, and CR/pathologic CR rate in the relapsed/refractory setting. Key secondary end points included event-free survival (EFS), OS, and safety.
To date, 20 frontline patients have been treated, 10 with relapsed/refractory disease, and 5 with CML-LBP, Short explained. The median age of the frontline cohort was 62 years [range, 34-83]. Among the 10 patients with relapsed/refractory Ph-positive ALL, 1 was primary refractory to [a] previous regimen, 4 were treated in first salvage, and 5 in second or later salvage. Among the 5 patients with CML-LBP, 3 had not received any prior therapy for blast phase disease, 1 was treated in first salvage, and 1 in second salvage.
Additional data indicated that the cohort of patients with CML-LBP had a CR or pathologic CR rate of 100%, as well as an MMR rate of 60%, and CMR rate of 40%. Moreover, the relapsed/refractory cohort achieved a rate of 88% in both MMR and CMR. In total, the overall patient population had a CR or pathologic CR rate of 96%, an MMR rate of 91%, and a CMR rate of 79%. No patients were reported to have an early death while on the study.
After the first cycle of treatment, the frontline ALL cohort had a CMR rate of 58%, an MMR rate of 26%, and 16% did not experience a response. Moreover, 75% of patients in the relapsed/refractory ALL cohort, and 20% in the CML-LBP cohort had a CMR after the first cycle, while 25% and 80% of patients from both cohorts did not respond, respectively.
Of the patients who experienced a CR or pathologic CR in the frontline ALL arm (n = 20), 1 died following CR due to post-procedural bleeding and hypovolemic shock, while 19 continue to experience ongoing responses without the need for stem cell transplantation. Notably, no patients in this have relapsed within 6 months.
In the relapsed/refractory ALL cohort, of the patients who responded (n = 9), 4 went on to receive HSCT, 1 of whom relapsed and died. Another patient relapsed and developed T315I and E255V mutations at relapse. Overall, 3 patients from this cohort are experiencing an ongoing response without the need for HSCT, while 1 patient died off study due to unknown causes.
In the CML-LBP arm, 2 responders (n = 5) relapsed, one of whom developed myeloid blast phase disease but is currently alive and in remission, while the other developed L248V and Y253H mutations at relapse but is currently alive and in remission following HSCT. Additionally, 3 patients continue to experience an ongoing response without HSCT.
After a median follow up of 12 months, the overall patient population is estimated to have 1- and 2-year EFS of 76% and 70%, respectively. Moreover, the estimated 1-year and 2-year OS were 93% and 80%, respectively. Notably, the relapsed/refractory AML cohort had an estimated 1- and 2-year EFS of 61% and 41%, respectively, as well as an estimated 1- and 2-year OS of 80% and 53%, respectively. Additionally, the CML-LBP arm had 60% estimated EFS rate at 1 and 2 years, respectively, as well as a 100% estimated 1- and 2-year rate.
Notably, there were no grade 4 or higher adverse effects (AEs) reported on the study. Common grade 3 AEs related to ponatinib in patients with ALL included elevated lipase (6%), alanine aminotransferase increase (ALT; 3%), cerebrovascular ischemia (3%), hypertension (3%) pancreatitis (3%), and deep vein thrombosis (3%). Grade 2 AEs included rash (11%), ALT increase (3%), and cerebrovascular ischemia (3%) and grade 1 AEs included rash (11%) and ALT increase (3%).
Although most AEs related to blinatumomab were grade 1 or 2 in patients with ALL, 1 patient developed grade 3 encephalopathy that was resolved by corticosteroids and treatment interruption, according to Short. Common grade 2 AEs included cytokine release syndrome (6%) and tremors (3%), as well as 1 patient who developed grade 1 tremors.
References
1. Short NJ, Kantarjian H, Konopleva MY, et al. Combination of ponatinib and blinatumomab in Philadelphia chromosome-positive acute lymphoblastic leukemia: Early results from a phase II study. Presented at: 2021 ASCO Annual Meeting; June 4-8, 2021; Virtual. Abstract 7001.
2. Daver N, Thomas D, Ravandi F, et al. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2015;100(5):653-651. doi:10.3324/haematol.2014.118588
3. Ravandi F, OBrien S, Cortes J, et al. Long-term follow-up of phase II study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia-chromosome positive acute lymphoblastic leukemia. Cancer. 2015;121(23):4158-4164. doi:10.1002/cncr.29646
4. Rousselot P, Coud MM, Gokbuget N, et al. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosomepositive ALL. Blood. 2016;126(6):774-782. doi:10.1182/blood-2016-02-700153
5. Jabbour E, Short NJ, Ravandi F, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: long-term follow-up of a single-centre, phase 2 study. Lancet Haematol. 2018;5(12):e618-e627. doi:10.1016/S2352-3026(18)30176-5
6. Martinelli G, Boissel N, Chevallier P, et al. Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol. 2017;35(16):1795-1802. doi:10.1200/JCO.2016.69.3531
7. Fo R, Bassan R, Vitale A, et al. Dasatinibblinatumomab for Ph-positive acute lymphoblastic leukemia in adults. N Engl J Med. 2020;383:1613-1623. doi:10.1056/NEJMoa2016272
Read the original post:
- 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
- Study finds interleukin-24 enhances CAR-T cell therapy's effectiveness against cancer stem cells - News-Medical.Net - February 15th, 2024
- Oldest Patient 'Cured' of HIV Still in Remission 5 Years After Transplant for AML - Medpage Today - February 15th, 2024
- Drug used for cocaine addiction may pave way for new treatment of advanced colon cancer - EurekAlert - February 15th, 2024
- Hematopoietic Stem Cells and Their Role in Development and Disease Therapy - The Scientist - February 15th, 2024
- Biomedical Researcher Seeks to Improve Outcomes in Stem Cell Treatments - University of Arkansas Newswire - February 13th, 2024
- Top 3 grants in regenerative medicine: January 2024 - RegMedNet - February 13th, 2024
- Scalise returning to Washington next week with cancer in complete remission - The Hill - February 13th, 2024
- Unlocking the power of stem cell therapy - Drug Target Review - February 9th, 2024
- Digging into the Dangers of Gene Therapy - The Medicine Maker - February 7th, 2024
- Treating and preventing abnormal heart beats with stem cell muscle grafts - Medical Xpress - February 7th, 2024
- Regeneration of the Retina Using Pluripotent Stem Cells: A Comprehensive Review - Cureus - February 3rd, 2024
- I thought I'll give it a chance - Liam Harrison reveals his thought process in getting crucial stem cell treatment - Sportskeeda - February 3rd, 2024
- Jennifer J. Raab named President and CEO of The New York Stem Cell Foundation - EurekAlert - February 3rd, 2024
- High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary ... - The Lancet - January 31st, 2024
- Houston regenerative medicine company to IPO, move toward more human trials - InnovationMap - January 31st, 2024
- New study on promising stem cell-based therapy for Crohn's disease - Medical Xpress - January 31st, 2024
- Exploring pharmacological, non-pharmacological, and stem cell therapies for treatment of autism spectrum disorders - News-Medical.Net - January 29th, 2024
- Stem cell study shows how gene activity modulates the amount of immune cell production in mice - Medical Xpress - January 26th, 2024
Recent Comments