Newly Diagnosed Multiple Myeloma (NDMM), Risk-Stratified

Evidence-based treatment sequencing for newly diagnosed multiple myeloma, integrating cytogenetic risk assessment and transplant eligibility to guide frontline quadruplet induction therapy (Dara-VRd), autologous stem cell transplantation, maintenance, and relapsed/refractory salvage.

Transplant eligibility and high-risk cytogenetic assessment

• Transplant-eligible candidate (fit performance status) → Daratumumab + Bortezomib + Lenalidomide + Dexamethasone (Dara-VRd)
• Transplant-ineligible or frail candidate → Daratumumab + Lenalidomide + Dexamethasone (Dara-Rd) or VRd-lite

1L: Daratumumab + Bortezomib + Lenalidomide + Dexamethasone (Dara-VRd)

Preferred frontline quadruplet induction for transplant-eligible NDMM (PERSEUS/GRIFFIN), delivering deep MRD-negative responses. Followed by autologous stem cell transplant consolidation in fit candidates.

• Completion of induction and evaluation for ASCT → Autologous stem cell transplantation (ASCT) and post-transplant maintenance

1L: Daratumumab + Lenalidomide + Dexamethasone (Dara-Rd) or VRd-lite

Preferred continuous frontline regimen for transplant-ineligible or frail patients (MAIA), with dose adjustment by comorbidity and frailty index.

• Disease progression or relapse → Disease progression / relapsed or refractory multiple myeloma (R/R MM)

Autologous stem cell transplantation (ASCT) and post-transplant maintenance

• Post-ASCT / sustained response maintenance → Lenalidomide ± daratumumab maintenance
• Disease progression following transplant → Disease progression / relapsed or refractory multiple myeloma (R/R MM)

maintenance: Lenalidomide ± daratumumab maintenance

Post-transplant (or post-induction) maintenance to prolong progression-free and overall survival; daratumumab may be added for high-risk cytogenetics.

• Disease progression on maintenance → Disease progression / relapsed or refractory multiple myeloma (R/R MM)

Disease progression / relapsed or refractory multiple myeloma (R/R MM)

• Relapsed/refractory multi-line salvage → BCMA CAR-T, bispecifics, or next-gen PI/IMiD salvage
• Clinical trial / palliative preference → Clinical trial / specialized salvage / supportive care

2L: BCMA CAR-T, bispecifics, or next-gen PI/IMiD salvage

Advanced salvage for relapsed/refractory disease: BCMA-directed CAR-T (idecabtagene vicleucel, ciltacabtagene autoleucel), BCMA/GPRC5D bispecific T-cell engagers (teclistamab, elranatamab), and next-generation proteasome-inhibitor / immunomodulatory combinations (carfilzomib, pomalidomide). Sequencing is guided by prior exposure and BCMA-targeting history.

• Subsequent progression → Clinical trial / specialized salvage / supportive care

3L+: Clinical trial / specialized salvage / supportive care

Clinical-trial evaluation or tailored multi-agent regimens for heavily pretreated, multi-refractory myeloma.