This year’s 67th ASH Annual Meeting and Exposition (ASH25), showcased transformative advances across multiple myeloma, chronic lymphocytic leukemia and small lymphocytic lymphoma, with bispecific antibodies, novel CAR T-cell strategies and next-generation targeted therapies redefining the treatment paradigm. Below, Prof Meletios-Athanasios Dimopoulos (National and Kapodistrian University of Athens, Athens, Greece) highlights several of the most impactful clinical trials, underscoring a shifting therapeutic landscape in diseases long marked by incremental progress.
“Teclistamab–daratumumab is poised to become a new standard of care for early-relapse myeloma”
Multiple myeloma
The combination of teclistamab and daratumumab has redefined the therapeutic landscape for relapsed or refractory multiple myeloma. In the phase III Majestec-3 trial (LBA-6) involving patients with 1–3 prior lines of therapy, this bispecific antibody regimen achieved a remarkable 36-month progression-free survival rate of 83.4% – nearly triple that of standard daratumumab-based combinations (29.7%). With complete response or better seen in over 80% of patients and minimal residual disease negativity in more than half, the depth and durability of responses are unprecedented. While serious adverse events were more frequent, the clinical benefit substantially outweighed the risks. These pivotal findings position teclistamab–daratumumab as a new standard of care for patients with multiple myeloma at early relapse.
Infection prophylaxis is essential for all patients with multiple myeloma who receive novel immunotherapies including bispecific antibodies and CAR-T cells. Infection prevention includes prophylactic administration of intravenous/subcutaneous immunoglobulin, and this is highly recommended as an upfront measure in all patients, especially those on anti-BCMA bispecific antibodies. This is also relevant for patients who receive the novel combination of teclistamab with daratumumab.
New CAR T-cells are on the horizon. Anito-cel showed significant activity and favourable safety profile, but randomized trials are needed in order to determine its position in the therapeutic algorithm. A proof-of-concept study of in vivo CAR-T cell also showed promising, albeit preliminary, results and is currently under investigation.
In the frontline treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), the phase III BRUIN CLL-313 trial (LBA-3) marks a significant turning point. Pirtobrutinib – a next-generation, highly selective noncovalent BTK inhibitor – achieved a dramatic improvement in progression-free survival over standard bendamustine-rituximab (BendaR) chemoimmunotherapy. With a 24-month PFS of 93.4% versus 70.7%, and fewer dose reductions, grade ≥3 adverse events, and treatment discontinuations, pirtobrutinib showed superior efficacy with enhanced tolerability. Even under a study design that allowed 52.9% crossover, a trend emerged towards improved overall survival favoring pirtobrutinib. These results establish pirtobrutinib as a highly effective and better-tolerated first-line option for CLL/SLL patients without del(17p), signaling a shift away from conventional chemoimmunotherapy.
ASH25 offered a glimpse into a rapidly evolving future for haematological malignancies. In multiple myeloma, bispecific antibodies such as teclistamab are establishing new standards of care, while next-generation CAR-T therapies hint at further breakthroughs. In CLL/SLL, pirtobrutinib’s impressive first-line performance signals yet another shift away from cytotoxic chemotherapy. Together, these data reflect a broader trend: immunotherapy and precision-targeted agents are increasingly delivering deeper, more durable responses with improved tolerability — a transformation likely to reshape clinical practice in the years ahead.
Disclosure: Meletios-Athanasios Dimopoulos is a member of the Advisory Board for Amgen, AstraZeneca, Beigene, BMS, GSK, Janssen, Menarini, Regeneron, Sanofi, Swixx and Takeda. He has received honoraria/honorarium from Amgen, AstraZeneca, Beigene, BMS, GSK, Janssen, Menarini, Regeneron, Sanofi, Swixx and Takeda.
Cite: ASH25 round-up: Late-breakers in multiple myeloma and CLL/SLL. December 16th, 2025
Related content
- Inside ASH25: Breakthroughs redefining transplantation and cell therapy
- CAR-T therapy: A new era for lymphoma
- ASH25: Top abstracts in non-malignant haematology
SIGN UP to touchHAEMATOLOGY!
Join our global community today for access to thousands of peer-reviewed articles, expert insights, and learn-on-the-go education across 150+ specialties, plus concise email updates and newsletters so you never miss out.
