Second relapse multiple myeloma

Authored by Vincent Rajkumar, published on 2026-10-16 00:33:40.0

Treatment algorithm for second relapse multiple myeloma. For BCMA sensitive, approach is similar to first relapse. For second relapse belantamab combinations provide an additional option. Consider salvage ASCT as alternative in patients eligible for ASCT who have not had transplant before; Consider 2°d auto SCT if eligible and had >36 months response duration with maintenance to first ASCT.Active drugs in multiple myeloma reference.mSMART 4.0 risk stratification of active multiple myeloma.Watch Dr. Rajkumar's intro video on Treatment of Multiple Myeloma Second Relapse (0:51).

  1. BCMA and Dara sensitive
    This is a clinical stratification node (sensitivity to BCMA-targeting and daratumumab) that sets up downstream therapeutic selection and sequencing. Guidelines support refractoriness-based regimen choice and earlier use of BCMA-directed therapies in appropriate patients. Watch Dr. Rajkumar's intro video on Treatment of Multiple Myeloma Second Relapse (0:51).
    • Tec-Dara, or BCMA CAR-T
  2. BCMA sensitive; Dara Refractory
    Guidelines support avoiding ineffective anti-CD38-based backbones in clearly daratumumab-refractory disease and prioritizing active BCMA-directed or non-cross-resistant regimens. Watch Dr. Rajkumar's intro video on Treatment of Multiple Myeloma Second Relapse (0:51).
    • BCMA CAR-T or Bispecifics,** or Belantamab combination or Standard triplet*
      **BCMA Bispecifics can be Teclistamab, Elranatamab, Linvoseltamab, or the Tec-Dara combination
  3. Refractory to BCMA Bispecific
    Expert guidance favors changing target or mechanism after BCMA-bispecific failure, especially after a short response. Reuse of another BCMA modality can work in selected patients but is supported mainly by nonrandomized evidence. Watch Dr. Rajkumar's intro video on Treatment of Multiple Myeloma Second Relapse (0:51).
    • Standard Triplet,* or Belantamab combination
      *Choice of standard triplet is based on refractoriness to Len, anti-CD38, and other drugs. Key options are DRd, KRd, KPd, DPd, Dara-KPd, and choose a triplet with at least two drugs the patient is not refractory to.
  4. Relapse after Prior BCMA CART
    Post-CAR-T therapy should account for response duration, residual cytopenias, infection risk, and possible BCMA antigen escape. Bispecific antibodies can retain activity after CAR-T, although responses are generally less certain than in BCMA-naive populations. Watch Dr. Rajkumar's intro video on Treatment of Multiple Myeloma Second Relapse (0:51).
    • Standard triplet,* or Belantamab combination, or Bispecifics**
      *Choice of standard triplet is based on refractoriness to Len, anti-CD38, and other drugs. Key options are DRd, KRd, KPd, DPd, Dara-KPd, and choose a triplet with at least two drugs the patient is not refractory to. **BCMA Bispecifics can be Teclistamab, Elranatamab, Linvoseltamab, or the Tec-Dara combination
tosprivacyIde-cel or Standard Regimens in Relapsed and Refractory Multiple MyelomaYouTube video: Multiple Myeloma Second Relapse: Vincent Rajkumar, MDTeclistamab plus Daratumumab in Relapsed or Refractory Multiple MyelomaTeclistamab in Relapsed or Refractory Multiple MyelomaDaratumumab plus Lenalidomide and Dexamethasone for Untreated MyelomaCilta-cel or Standard Care in Lenalidomide-Refractory Multiple MyelomaBelantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma