The past year in hematologic oncology combined breakthrough clinical advances with heightened regulatory scrutiny, underscoring efforts to overcome treatment resistance and refine risk–benefit assessments. New agents and regimens produced practice-changing results across myeloma, leukemia and essential thrombocythemia, while advisory panels raised important questions about trial generalizability and toxicity management.
BTK degraders show promise against resistance
Early-phase data on Bruton tyrosine kinase (BTK) degraders highlighted a potential new strategy for patients who progress on BTK inhibitors. Agents such as BGB-16673 produced high overall response rates, including a reported 77.6% ORR in relapsed/refractory CLL/SLL, and showed activity in patients previously exposed to BTK inhibitors. By directing cellular machinery to destroy the BTK protein, degraders may overcome resistance mutations that blunt traditional inhibitors, and early safety profiles appeared manageable.
ODAC finds STARGLO trial results not generalizable to U.S. patients with DLBCL
The FDA’s Oncologic Drugs Advisory Committee voted 8–1 that the phase 3 STARGLO trial of glofitamab plus GemOx in relapsed/refractory diffuse large B‑cell lymphoma is not reliably applicable to U.S. practice. Although the trial met its primary endpoint—reporting median overall survival of 25.5 months versus 12.9 months with rituximab plus GemOx—the committee cited regional enrollment imbalance (only 9% of patients enrolled in the U.S. versus 48% in Asian regions) and markedly higher efficacy in some regions, concluding the results lack sufficient generalizability for U.S. patients.
ODAC raises safety concerns for belantamab mafodotin despite approval
Advisors concluded that the benefit–risk profile of belantamab mafodotin combinations in early relapsed/refractory multiple myeloma was unfavorable, citing frequent, severe ocular toxicity (keratopathy) and high rates of dose modifications exceeding 75% in DREAMM-7 and DREAMM-8. The committee determined proposed dosing had not adequately mitigated ocular risk and voted against a favorable risk–benefit assessment. The FDA subsequently approved the agent in October.
Transplantation linked to improved survival in plasma cell leukemia
A retrospective analysis of primary and secondary plasma cell leukemia (pPCL and sPCL) documented stark survival differences: median overall survival was 36.6 months for pPCL versus 3.2 months for sPCL. Hematopoietic stem cell transplantation was strongly associated with better outcomes, extending median OS to 48.7 months in the transplanted cohort across both subtypes, with no clear difference in benefit between autologous and allogeneic approaches. The findings reinforce transplantation’s prognostic importance and the urgent need for better therapies, particularly for sPCL.
Ropeginterferon alfa-2b outperforms anagrelide in essential thrombocythemia
The SURPASS-ET phase 3 trial showed ropeginterferon alfa-2b achieved a durable clinical response in 42.9% of patients at 9 and 12 months versus 6% for anagrelide, meeting its primary endpoint. Ropeginterferon also produced greater reductions in JAK2 V617F allele burden and had a manageable safety profile. Already approved for polycythemia vera, the agent’s manufacturer plans to pursue FDA label expansion for essential thrombocythemia.
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