How do you approach the second-line treatment for a patient with high-risk myeloma relapse early post-autoHCT after Dara-RVD induction?

Depending on the nature of the relapse, I would salvage with DCEP, or carfilzomib-based triplet (KCyD, KPd) with ciltacel as the next step.

Agree with @Dr. First Last. I typically prefer Dara-KPd or KCd as holding therapy and a bridge to cilta-cel. The subgroup data from CARTITUDE-4 showed that patients with early relapse post-ASCT (defined as <18 months) benefited greatly from cilta-cel (Einsele et al., PMID 41519141) - the 12-month PFS was 77%, with mPFS not reached! An updated analysis of CARTITUDE-4 high-risk patients found the mPFS was 37 months, again superior to standard of care (Sidana et al., ASCO, 2025).

This is clearly a patient with functional high-risk disease. If the patient is eligible to undergo a CAR-T cell therapy, that would be my preference. If you're detecting the relapse early on and the disease burden is still relatively low, I would go ahead with the therapy without any specific bridging therapy and would continue the patient for an additional cycle or two of what they are currently on. If the disease burden is felt to be on the higher side, then a bridging therapy with a combinati...

I strongly favor cilta-cel in this scenario. Tec-Dara remains an interesting alternative, but even with the MajesTEC-9 results, we don't fully understand the benefit that Dara adds in the setting of refractoriness to it. Second, we don't have absolute PFS data for the high-risk subgroup (only that it outperformed the standard of care). Cilta-cel has this subgroup data (mPFS 36 months for high-risk disease and substantially less - ~12 months - for EMD), and was carried out at least in a populatio...

I believe non-BCMA-targeting bispecific antibody combinations will become the preferred treatments in this setting. These can be used either as bridging therapies for CAR-T cell therapy or as definitive therapies. The choice might be determined upfront or deferred pending depth of response (MRD status) during the early phase of treatment. Given increasing use of daratumumab in maintenance, promising non-BCMA and non-anti-CD38 combinations are of most interest. Recent presentations of pomalidomid...