Treatment of Myeloma: First Relapse

Authored by Vincent Rajkumar, published on 2026-02-27 19:26:32.0

Updated 2025 treatment algorithm for multiple myeloma patients with first relapse. Based on recent data presented at ASH 2025 about the MajesTEC-3 trial which showed higher PFS for patients using the tec-dara combination.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

  1. Not Refractory to Anti-CD38
    • Unable to give cell therapy and bispecifics per guidelines
      • Standard Triplet**
        **Choice of standard triplet is based on refractoriness to Len and other drugs. Key options are DRd, KRd, KPd, DPd, Dara-KPd.
    • Have access, and able to give cell therapy and bispecific per recommended guidelines
      • Cilta-cel* or Tec-Dara
        *Cilta-cel should be considered in eligible patients, and patients should have a discussion on pros and cons of a one-time CART approach vs prolonged therapy.
  2. Refractory to Anti-CD38
    • Have access, and able to give cell therapy per recommended guidelines
      • Cilta-cel* or Standard triplet**
        *Cilta-cel should be considered in eligible patients, and patients should have a discussion on pros and cons of a one-time CART approach vs prolonged therapy. **Choice of standard triplet is based on refractoriness to Len and other drugs. Key options are DRd, KRd, KPd, DPd, Dara-KPd.
    • Unable to give cell therapy per guidelines
      • Standard Triplet**
        **Choice of standard triplet is based on refractoriness to Len and other drugs. Key options are DRd, KRd, KPd, DPd, Dara-KPd.
tosprivacyTeclistamab plus Daratumumab in Relapsed or Refractory Multiple MyelomaCilta-cel or Standard Care in Lenalidomide-Refractory Multiple MyelomaA Study of Teclistamab in Combination With Daratumumab Subcutaneously (SC) (Tec-Dara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-3)A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma (CARTITUDE-4)