Abstract: Dr. Nicholas Short delves into the forefront of advancements in the treatment of Acute Lymphoblastic Leukemia (ALL) at the EHA Congress 2023. He discusses the evolution of therapeutic strategies, particularly in B cell ALL, where various agents like blinatumomab, inotuzumab ozogamicin, and CD19 CAR T cell products have demonstrated notable efficacy. Notably, the focus on Philadelphia Chromosome-positive ALL introduces potent tyrosine kinase inhibitors like ponatinib, exhibiting promising outcomes surpassing earlier treatments. Further, Dr. Short presents compelling insights into an ongoing study exploring a chemotherapy-free regimen using ponatinib and blinatumomab for newly diagnosed Ph-positive ALL patients. This regimen showcases high response rates and deep molecular responses, potentially redefining the standard of care without the necessity of transplantation in initial remission. Additionally, he emphasizes the emergence of CAR-T cell therapies targeting T cell ALL, addressing a longstanding therapeutic gap. These advances herald promising directions in the ALL landscape, presenting novel possibilities for improved treatment modalities.
Oncology Frontier: Our first question is about, could you please talk about the latest advances of target agents in ALL (acute lymphoblastic leukemia) treatment at this EHA congress?
Dr. Short: We’ve had a lot of improvements in the outcomes with patients with ALL particularly in B cell ALL. A lot of new studies evaluating different combinations using blinatumomab, which is a CD19/CD3 bispecific engaging antibody, inotuzumab ozogamicin, which is an anti CD 22 antibody drug conjugate.And then also there’s several CD 19 CAR T cell products that are approved in various countries. Now we’re seeing data from some other different CAR T cell constructs.And in Philadelphia Chromosome positive ALL, we have different TKIs available that target BCR-ABL. In particular, we’re seeing a lot of interest and excitement around ponatinib. Ponatinib is a very potent tyrosine kinase inhibitor that across study seems to yield better outcomes than those with earlier generation TKIs. In fact, we had a large randomized study showing the benefit of ponatinib compared to imatinib in Ph positive ALL so that may represent a new standard of care for these patients.
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Oncology Frontier: Could you please talk about an oral study which was reported by your team and evaluated the efficacy of chemotherapy-free combination of ponatinib and blinatumomab for patients with newly diagnosed philadelphia chromosome-positive acute lymphoblastic leukemia?
Dr. Short: So we presented updated data from our ongoing study of a chemotherapy-free regimen of ponatinib and blinatumomab in patients with newly diagnosed Ph positive ALL. We give five cycles of immunotherapy with blinatumomab in combination with ponatinib, 30 milligrams daily initially, then we decrease the dose to 15 milligrams once the patients achieved a complete molecular response. We give 12 doses of intrathecal, chemotherapy prophylaxis. We’ve seen very high rates of response. Essentially, all patients have responded.The complete molecular response rate, which is MRD (minimal residual disease) negativity by PCR for BCR-ABL is 87%.And when we look even more sensitive with next generation sequencing MRD that’s sensitive at one out of a million, we have a MRD negativity rate of 89%, so we see very deep MRD responses.
Importantly, we’ve also only transplanted one of the 60 patients that we’ve treated. So we’re delivering this chemotherapy-free regimen also without transplant in first remission. We’ve seen very few relapses of the relapse is that we’ve seen. There’s been disproportionate in the central nervous system. This is a concern with chemotherapy-free regimens, but we’re now amending the study to increase the total doses of intrathecal chemotherapy.But that said the 2 year overall survival is 88%, which is very encouraging, particularly with the chemotherapy-free regimen that can overcome the need for transplants. So we really think that these chemotherapy-free regimens will likely be the new standard of care, going forward for patients with Ph positive ALL and also hopefully most patients with Ph positive ALL won’t need a transplant in the near future.
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Oncology Frontier: Could you please introduce us some therapeutic progress or any advance of target treatment in the field of the ALL at this EHA congress?
Dr. Short: There’s two different CAR-T cell products that are at least approved in the US and around various other countries.These are both target CD19. One is called tisagenlecleucel. One is brexucabtagene autoleucel. The big question going forward is how should we best use these drugs.Should we use them, for example, as consolidation rather than for patients with relapse/refractory disease? Should we move them into the frontline setting again as consolidation, and maybe they can overcome the need for stem cell transplant? Those are all active questions that are being asked now.
I think one thing that’s particularly interesting at this particular conference was we’ve seen some data presented about CAR-T cells that can target T cell ALL and this has really been an unmet need.In patients with ALL we have a lot of good therapies now. For patients with B cell ALL, again inotuzumab, blinatumomab, CD19 CAR-T cells, but very few effective drugs for patients with T cell ALL and so there was just data presented about CD5 CAR-T cell that showed some encouraging response rates. We’ve seen previously some other early data of CD9/CD7 CAR-T cells. So it’ll be exciting to see what happens in the future with these. None of these are approved yet, but this is certainly an unmet need in the treatment of patients with relapse/refractory ALL.
TAG: EHA 2023, Interview, Hematological Malignancy, ALL
