BCMA-directed therapies are reshaping how myeloma is treated — and where

The relapsed/refractory multiple myeloma (R/R MM) landscape has been transformed by a wave of BCMA-directed therapies, but with more options comes more complexity. At a recent OncLive Peer Exchange, leading myeloma specialists broke down how to choose among CAR T-cell therapies, bispecific antibodies, and antibody-drug conjugates (ADCs) — and how to sequence them smartly. Key factors include disease biology, urgency, patient geography, and access to caregivers. For patients who can't easily reach academic centers, off-the-shelf bispecifics and ADCs offer a critical lifeline.

Longer-term data are bolstering confidence in these agents. In the DREAMM-7 trial, belantamab mafodotin plus bortezomib and dexamethasone delivered a median PFS of 36.6 months vs. 13.4 months for the comparator arm. Meanwhile, teclistamab monotherapy showed an unprecedented hazard ratio of 0.29 for PFS in earlier-line disease. Experts also highlighted that belantamab mafodotin doesn't appear to exhaust T-cells or deplete BCMA expression, potentially preserving future immunotherapy options.

On the delivery side, prophylactic tocilizumab before bispecific step-up dosing has dramatically cut cytokine release syndrome (CRS) rates — from ~75% down to ~15% at some centers — enabling true outpatient administration. Community practices are building infrastructure around caregiver education, home monitoring, and hospital handoff protocols to make this scalable.

Key Takeaways

• Infection — not CRS — is the dominant long-term risk with bispecific antibodies; IVIG prophylaxis should accompany every BCMA-directed bispecific
• Belantamab mafodotin preserves BCMA expression at progression, keeping future CAR T or bispecific options open
• Prophylactic tocilizumab is now NCCN-endorsed, removing insurance coverage as a barrier to outpatient use
• Trispecific antibodies (e.g., ramantamig targeting BCMA, GPRC5D, and CD3) are emerging as the next frontier

Why it matters: As bispecifics move into earlier lines of therapy, the eligible patient population is expected to grow substantially. Expanding safe, community-based delivery is no longer optional — it's essential to ensuring equitable access to these life-extending therapies.