Multiple Myeloma Treatment Landscape: Standard and Emerging Therapies

Multiple myeloma (MM) is a plasma cell malignancy. While incurable, outcomes have dramatically improved with triplet/quadruplet regimens, transplant, and novel agents.

Standard-of-Care Framework

• Induction (newly diagnosed): VRd (bortezomib/lenalidomide/dex) or DRd (daratumumab/len/dex) for transplant-eligible; DRd or VRd-lite for ineligible.
• Autologous stem cell transplant (ASCT): Standard for eligible patients; improves PFS/OS.
• Maintenance: Lenalidomide until progression (standard); consider adding daratumumab/bortezomib for high-risk.
• Relapsed/refractory: Sequential lines: anti-CD38 (daratumumab, isatuximab), PIs (carfilzomib, ixazomib), IMiDs (pomalidomide), Selinexor, belantamab (withdrawn US), clinical trials.

Emerging/Novel Modalities

• BCMA-targeted CAR-T: Idecabtagene vicleucel, ciltacabtagene autoleucel (≥4 prior lines). Deep, durable responses.
• Bispecific antibodies: Teclistamab (BCMA×CD3), talquetamab (GPRC5D×CD3), elranatamab. Off-the-shelf, continuous dosing.
• Next-gen PIs/IMiDs: Melflufen (withdrawn), iberdomide, mezigdomide.
• Cereblon E3 ligase modulators (CELMoDs): Enhanced degradation of Ikaros/Aiolos.
• BCL-2 inhibitors: Venetoclax (t(11;14) subset).

Supportive Care Essentials

• Bone health: zoledronic acid/denosumab.
• Infection prophylaxis: antivirals (acyclovir), PJP (TMP-SMX), IVIG if hypogammaglobulinemia.
• Neuropathy monitoring (bortezomib); VTE prophylaxis (IMiDs).

Personalized Approach

Risk stratification (R-ISS, cytogenetics: del17p, t(4;14), t(14;16), gain 1q), frailty, comorbidities, patient goals guide regimen selection. Clinical trial participation encouraged at all stages.