Treatment of Myeloma: First Relapse

Authored by Vincent Rajkumar, published on 2026-06-09 21:42:04.0

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
      • Standard Triplet**
        ** Choice of standard triplet is based on refractoriness to Len, anti-CD38, and other drugs. Key options are DRd, KRd, KPd, Anti CD38-Pd, Anti CD38-Kd, EloPd, Dara-KPd, PI-Cd and choose a triplet with at least two drugs the patient is not refractory to.
    • Have access, and able to give cell therapy and bispecifics
      • BCMA CART* 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
      • BCMA CART* or BCMA Bispecific
        *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.
    • Unable to give cell therapy and bispecifics
      • Standard Triplet**
        ** Choice of standard triplet is based on refractoriness to Len, anti-CD38, and other drugs. Key options are DRd, KRd, KPd, Anti CD38-Pd, Anti CD38-Kd, EloPd, Dara-KPd, PI-Cd and choose a triplet with at least two drugs the patient is not refractory to.
  3. Consider salvage ASCT as alternative in patients eligible for ASCT who have not had transplant before
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)Ide-cel or Standard Regimens in Relapsed and Refractory Multiple MyelomaA 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)Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma