Oncology (Williston Park). 2026 May 29. 40(4):
BACKGROUND: Bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR) T-cell therapies have transformed the management of hematologic malignancies, including relapsed/refractory multiple myeloma (RRMM), lymphomas, and leukemias. These approaches enable targeted cytotoxicity through T-cell redirection and engineered cellular activity, achieving high response rates in heavily pretreated populations. Data presented at the 2025 Immune Cell Effector Therapies (ICE-T) Symposium highlighted expansion beyond B-cell maturation antigen (BCMA) to additional targets such as GPRC5D and FcRH5, alongside emerging multitarget and next-generation constructs aimed at improving durability and overcoming resistance.
METHODS: This narrative review summarizes key findings from the 2025 ICE-T Symposium, integrating data from clinical trials, real-world studies, and contemporary guideline-based management, with a focus on efficacy, safety, sequencing, and emerging therapeutic platforms.
RESULTS: Across hematologic malignancies, immune-based therapies demonstrated substantial and clinically meaningful activity, with outcomes varying by disease subtype, target antigen, and therapeutic platform. In multiple myeloma, BCMA-directed bispecific antibodies, including teclistamab and elranatamab, achieved overall response rates (ORRs) of approximately 63% and 61%, respectively, in heavily pretreated populations, with median progression-free survival (PFS) of approximately 11 to 17 months across pivotal studies. Talquetamab demonstrated ORR of approximately 73% to 74% in the MonumenTAL-1 study (NCT03399799), supporting efficacy in post-BCMA settings. Cevostamab has shown promising early-phase activity, with response rates of approximately 55% to 60% at higher dose levels, reflecting the expansion of therapeutic targets beyond BCMA. In B-cell lymphomas, CD19-directed CAR T-cell therapies, including axicabtagene ciloleucel and lisocabtagene maraleucel, produced high response rates with durable remissions in relapsed/refractory large B-cell lymphoma, with long-term follow-up demonstrating sustained survival in a subset of patients. Among bispecific antibodies, epcoritamab achieved an ORR of approximately 60% to 65%, whereas glofitamab demonstrated an ORR of approximately 45% to 50% in heavily pretreated populations, supporting their role as effective off-the-shelf therapeutic options. In acute lymphoblastic leukemia, CD19-directed CAR T-cell therapies, including tisagenlecleucel and brexucabtagene autoleucel, achieved high rates of remission with deep measurable residual disease negativity, supporting their role as definitive or bridging strategies in relapsed disease. Beyond hematologic malignancies, early-phase data highlighted the expansion of T cell-redirecting therapies into solid tumors. The DLL3-directed bispecific antibody tarlatamab demonstrated clinically meaningful activity in relapsed small cell lung cancer and has received accelerated regulatory approval based on response rate and durability. Safety profiles were broadly consistent across platforms. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were frequent but predominantly low grade and manageable with IL-6 blockade and corticosteroids. Infections and prolonged cytopenias represented the principal drivers of morbidity, emphasizing the need for structured supportive care. Contemporary recommendations from the NCCN and International Myeloma Working Group support proactive toxicity mitigation, antimicrobial prophylaxis, and multidisciplinary management. Emerging strategies, including trispecific antibodies, dual-target CAR T-cell constructs, and allogeneic "off-the-shelf" cellular therapies, demonstrated promising early efficacy and represent key approaches to improving durability, overcoming resistance, and expanding access across hematologic malignancies.
CONCLUSIONS: T cell-redirecting therapies represent a central pillar in modern oncology, delivering high response rates across hematologic malignancies with expanding roles in earlier treatment settings. Future progress will depend on improving durability, optimizing sequencing, mitigating toxicity, and enhancing real-world deliverability through next-generation and multitarget platforms.