Highlights from American Society of Hematology 2021 Meeting

Hematology Research in Lab

The 63rd American Society of Hematology (ASH) Annual Meeting and Exposition is wrapping up today. Dozens, even hundreds, of updates were provided on clinical trials and preclinical research. Here’s a highlight of just a few of those stories.

The Janssen Pharmaceutical Companies of Johnson & Johnson and Legend Biotech announced longer-term results from the Phase Ib/II CARTITUDE-1 study of ciltacabtagene autoleucel in relapsed or refractory (r/r) multiple myeloma. The therapy is a B-cell maturation antigen (BCMA)-directed CAR-T therapy given in a single infusion.

“Unfortunately, patients with multiple myeloma for whom at least three treatment regimens have stopped working, face a median survival of less than a year with currently available treatments,” said Thomas Martin, director of Clinical Research, Clinical Professor of Medicine, Adult Leukemia and Bone Marrow Transplantation Program, Associate Director, Myeloma Program and Co-Leader, Hematopoietic Malignancies Program, at UCSF Helen Diller Family Comprehensive Cancer Center, and principal study investigator. 

“The CARTITUDE-1 data presented at ASH 2021 builds upon previous results that show that a single infusion of cilta-cel resulted in durable responses and long-term survival across the study population, further confirming the potential of cilta-cel in offering patients and physicians a valuable new treatment option.”

Global Blood Therapeutics (GBT) announced positive results from real-world and long-term studies of Oxbryta (voxelotor) for sickle cell disease (SCD). Oxbryta is a first-in-class oral, once-daily therapy that directly inhibits sickle hemoglobin polymerization. The retrospective analysis of 3,128 SCD patients receiving the drug demonstrated a statistically significant improvement in hemoglobin levels and significant reductions in transfusions, vaso-occlusive crises and hospitalizations. They also presented Phase I data for inclacumab, the company’s P-selectin inhibitor, for the reduction of VOCs in SCD patients. It had a well-tolerated safety profile.

The University of Texas MD Anderson Cancer Center presented three clinical studies of Gilead Sciences/Kite's Yescarta (axicabtagene ciloleucel (axi-cel)) CAR-T. This included the ZUMA 1 study in r/r large B-cell lymphoma; follow-up data from the Phase II ZUMA-5 trial in r/r indolent non-Hodgkin lymphoma; and the Phase III ZUMA-7 trial in LBCL. The ZUMA-5 demonstrated long-term survival benefits in the patients with r/r indolent NHL who failed two or more previous lines of therapy. 

“Indolent non-Hodgkin lymphoma is a slow-developing chronic disease in which patients frequently relapse, which leads to the need for new treatment strategies,” said Saatva Neelapu, professor of Lymphoma and Myeloma at MD Anderson.

The ZUMA 12 trial expanded on ZUMA-1 findings as first-line therapy of axi-cel for high-risk LBCL. The study demonstrated a high rate of rapid and complete responses. And the ZUMA-7 trial demonstrated a clinically significant advantage in event-free survival (EFS) relative to standard of care (SOC) high-dose chemotherapy with autologous stem cell transplant.

Regeneron Pharmaceuticals announced new results for higher dose level cohorts of the Phase I portion of the Phase I/II trial of REGN5458 in r/r multiple myeloma. The drug is a bispecific antibody. The study found a 51% overall response rate (ORR) across all dose groups, rising to 75% in patients receiving the higher dose.

“Patients with multiple myeloma often face a long and challenging journey, with most becoming refractory to multiple lines of therapy over time,” said Jeffrey Zonder, professor of Oncology at the Karmanos Cancer Institute in Detroit, Michigan, and a trial investigator. “Today’s REGN5458 data show promising response rates, particularly at the higher dose levels, in patients with a high disease burden and highly refractory disease who otherwise would have very limited options available.”

Bristol Myers Squibb announced early results from an interim analysis of the Phase III TRANSFORM trial of Breyanzi (lisocabtagene maraleucel; liso-cel), a CD19-directed CAR-T therapy as second-line treatment in r/r LBCL compared to standard of care. The drug significantly improved event-free survival (EFS).

“For more than 20 years, salvage chemotherapy followed by high-dose chemotherapy and stem cell transplant have been the mainstay of care for patients with second-line relapsed or refractory LBCL, but only a small portion of patients experience long-term benefit with this approach,” said Manali Kamdar, lead investigator and associate professor, Clinical Director of Lymphoma Services, Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation, University of Colorado Cancer Center. 

“With liso-cel outperforming the current standard of care for patients with hard-to-treat disease in the TRANSFORM study, these results may pave the way for a practice-changing treatment approach where patients whose disease relapses or is refractory to frontline therapy can be treated with a personalized CAR T cell therapy to increase the potential for improved outcomes.”

Precigen presented positive interim data from its ongoing Phase I/Ib trial of PRGN-3006 UltraCAR-T in r/r acute myeloid leukemia (AML) and higher risk myelodysplastic syndromes. The therapy is a multigenic autologous CAR-T that simultaneously expresses a CAR that targets CD33 and membrane bound IL-15, and a kill switch to conditionally eliminate CAR-T cells to improve the safety profile. The presentation included data from 15 r/r AML patients in the non-lymphodepletion and lymphodepletion cohorts.

“The interim data for PRGN-3006 showed excellent, dose-dependent expansion and persistence of PRGN-3006 in peripheral blood and bone marrow following a single infusion, with detection of UltraCAR-T cells in blood more than three months post-infusion in the non-lymphodepletion and lympodepletion cohorts,” said David A. Sallman, lead investigator and assistant member in the Department of Malignant Hematology at the H. Lee Moffitt Cancer Center & Research Center.

Fate Therapeutics presented positive interim Phase I data from its FT596 program for r/r B-cell lymphoma. The therapy is an off-the-shelf, multi-antigen targeted, iPSC-derived natural killer cell product derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a CAR optimized for NK cell biology that targets CD19; a high-affinity, non-cleavable CD16 Fc receptor modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion.

Atara Biotherapeutics announced efficacy and safety results from its Phase III ALLELE study of tabelecleucel (tab-cel) for Epstein-Barr virus positive post-transplant lymphoproliferative disease after a solid organ transplant or hematopoietic cell transplant.

“Patients with EBV+ PTLD face a poor prognosis with survival measured in weeks to months if initial treatment is unsuccessful,” said Jakob Dupont, head of Global Research & Development at Atara. “There are no approved treatment options for this devastating disease, underscoring the critical unmet need that exists.”

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