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ASH 2024: Novel Therapies and Strategies Advance Hematologic Cancer Treatment

  • Bispecific T-cell engagers show promising real-world outcomes for relapsed/refractory large B-cell lymphoma, offering a new treatment avenue.
  • Menin-MLL inhibitors like enzomenib demonstrate encouraging Phase 1 results in relapsed/refractory acute leukemia, potentially altering treatment paradigms.
  • Odronextamab monotherapy exhibits efficacy in diffuse large B-cell lymphoma progressing after CAR T-cell therapy, addressing a critical unmet need.
  • Studies highlight the impact of novel combinations and targeted therapies in improving outcomes for various lymphoma subtypes and multiple myeloma.
The 66th American Society of Hematology (ASH) Annual Meeting showcased groundbreaking research and therapeutic advancements in hematologic malignancies. Several presentations highlighted novel treatment strategies and improved outcomes for patients with various blood cancers.

Bispecific T-Cell Engagers in Large B-Cell Lymphoma

Real-world data from the REALBiTE study (Abstract 111) demonstrated the effectiveness of bispecific T-cell engagers in patients with relapsed or refractory large B-cell lymphoma (LBCL). This multi-center, retrospective cohort study provided insights into the outcomes of patients treated with these agents outside of clinical trials, suggesting a promising role for bispecific antibodies in LBCL management.

Menin-MLL Inhibitors in Acute Leukemia

Enzomenib (DSP-5336), a Menin-MLL inhibitor, showed encouraging Phase 1 results in patients with relapsed or refractory acute leukemia (Abstract 213). This first-in-human study indicates the potential of Menin-MLL inhibition as a novel therapeutic strategy in acute leukemia. Additionally, interim Phase 1a results from the KOMET-007 trial (Abstract 214) explored ziftomenib combined with intensive induction chemotherapy in newly diagnosed NPM1-mutated or KMT2A-rearranged acute myeloid leukemia (AML), suggesting a potential benefit in this specific AML subgroup.

CAR-T Therapy and Post-Progression Strategies in Lymphoma

Research presented in Abstract 238 focused on treatment patterns and outcomes following progression of disease post-CAR-T therapy in relapsed or refractory mantle cell lymphoma (MCL). This multi-center analysis provides valuable information for clinicians managing patients who have relapsed after CAR-T treatment. Abstract 473 further examined the efficacy, toxicity, and predictors of outcomes with CD3-CD20 bispecific antibodies post CAR T-cell failure for aggressive B-cell lymphoma.

Odronextamab in Diffuse Large B-Cell Lymphoma

The ELM-1 study (Abstract 866) presented primary analysis data on odronextamab monotherapy in patients with diffuse large B-cell lymphoma (DLBCL) progressing after CAR T-cell therapy. The results demonstrated clinically meaningful activity, offering a potential treatment option for patients with limited alternatives. Long-term data from the ELM-1 and ELM-2 studies (Abstract 3118) further supported the efficacy and safety of odronextamab in relapsed/refractory DLBCL.

Advancements in Follicular Lymphoma Treatment

Abstract 341 highlighted escalating doses of AZD0486, a novel CD19xCD3 T-cell engager, resulting in high complete remissions with rapid clearance of minimal residual disease in patients with relapsed/refractory follicular lymphoma. Additionally, Abstract 4407 showed that mosunetuzumab continues to demonstrate clinically meaningful outcomes in patients with relapsed and/or refractory follicular lymphoma after two prior therapies, including those with a history of POD24, with 4-year follow-up data from a pivotal Phase II study.

Multiple Myeloma Therapies

Abstract 256 investigated the effects of intravenous immunoglobulin supplementation (IVIG) on infections in recipients of teclistamab therapy for multiple myeloma (MM). The multi-institutional study provided insights into managing infection risk in patients receiving teclistamab. Furthermore, Abstract 3369 presented longer follow-up data and selected high-risk subgroup analyses of linvoseltamab in patients with relapsed/refractory multiple myeloma from the Linker-MM1 study.

Other Notable Findings

  • The POLARIX study (Abstract 469) presented a five-year analysis confirming the positive impact of polatuzumab vedotin plus R-CHP on outcomes in diffuse large B-cell lymphoma.
  • Real-world outcomes of lisocabtagene maraleucel (liso-cel) as second-line therapy in relapsed/refractory LBCL were reported from the CIBMTR Registry (Abstract 470).
  • Abstract 307 evaluated the efficacy and toxicity of fixed dose versus reduced/PK-adjusted dose pegaspargase in pediatric patients with newly diagnosed acute lymphoblastic leukemia.
The data presented at ASH 2024 underscores the rapid progress in hematologic cancer research, with novel therapies and treatment strategies poised to improve patient outcomes across a range of blood malignancies.
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[2]
Rutgers Cancer Institute and RWJBarnabas Health to Unveil Pioneering Blood Cancer Research
rwjbh.org · Nov 27, 2024

Oral and poster presentations on various studies in hematology, including outcomes with bispecific T-cell engagers, phas...

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