The multiple myeloma (MM) landscape continues to evolve at a rapid pace. Key data presented at ASH spanned CAR-T therapies (long-term data from CARTITUDE-4, iMMagine-1), bispecific antibodies (MAJESTEC-3), antibody–drug conjugates (long-term data from DREAMM-7 & 8), and next-generation modalities, including in vivo CAR-T and dual-targeted CAR-T constructs.
ASH ’25: Shaping today’s treatment decisions
Bringing treatment into the community
Bispecific antibodies are rapidly gaining traction in the relapsed and refractory multiple myeloma space, with teclistamab (Tecvayli) leading the way. The results from MAJESTEC-3 mark a real turning point: the first bispecific combination to move to 2L and achieve an unprecedented PFS hazard ratio of 0.17. From the moment the abstract was first released, it captured widespread attention. Clinicians, especially in community settings, are taking note, as these findings promise to make highly effective therapy more accessible outside major academic centers.
Increased competition and complex decision-making in 2L
The 2L relapsed/refractory MM space is becoming increasingly competitive. Clinicians are weighing CAR-T therapies, bispecific antibodies, Blenrep, and standard triplets, with sequencing a central question. While MAJESTEC-3 has raised the bar, CAR-T offers durable remissions, treatment-free intervals, and a window for immune recovery. Furthermore, its effectiveness and manufacturing can be affected if a bispecific is given first. Blenrep, similar to BsAb, is off-the-shelf but does not require continuous therapy, making it a practical option for patients who may struggle with ongoing treatment. In practice, 2L decision-making requires a multilayered approach, integrating scientific evidence, access realities, and patient-centered priorities.
Safety as a strategic differentiator
ASH provided important updates on safety across T-cell–directed therapies. As efficacy across options continues to converge, the ability to deliver potent treatments safely is emerging as an important differentiator.
- Anito-cel, set to enter as the third BCMA CAR-T, delivered the signal many were watching for: no cases of delayed neurotoxicity reported in iMMagine-1 to date. If this holds, it may give anito-cel the edge it needs to challenge Carvykti.
- Safety progress was also a theme for Tecvayli. While infection risk has been a concern, particularly in community practice, new approaches such as Q4 dosing and IVIG prophylaxis are improving tolerability. MAJESTEC-3 showed that infections remain present but can be effectively managed with the right strategies.
ASH ’25: Shaping the future MM landscape
ASH also provided early data signals pointing to the next phase of multiple myeloma treatment.
- In vivo CAR-T: Next-generation in vivo CAR-T approaches could transform accessibility by removing the need for ex vivo manufacturing and lymphodepletion. Early data from the inMMyCAR study are fuelling strong interest, hinting at a future where CAR-T could be delivered in standard hospital settings, widening access and reducing treatment delays.
- Dual-targeted CAR-T: Dual-targeted CAR-T constructs aim to counter antigen escape and prolong responses. At ASH, AZD0120 showed encouraging activity in both BCMA-naive and BCMA-exposed patients. However, the regulatory landscape for future CAR-T therapies may be set to become stricter, adding complexity to the path to market.
Navigating the path forward
The multiple myeloma landscape is evolving rapidly, with growing complexity in the 2L relapsed/refractory setting. Future 2L patients, i.e., quad-treated populations, are still emerging, even as the 2L armamentarium expands, and predictions of future care pathways are a topic of active discussion. For clinical teams, subset analyses and strategic sequencing trials will help identify where therapies can have the greatest impact. For brand teams, maintaining clear value and differentiation remains critical to navigate this dynamic market.
If you’d like to discuss these developments and reflections, our oncology team is always up for a conversation.