The incorporation of anti-CD38 monoclonal antibody therapy into frontline treatment for transplant-ineligible multiple myeloma has transformed outcomes. The phase 3 MAIA trial established the anti-CD38 monoclonal antibody plus lenalidomide-dexamethasone (DRd) triplet as a standard of care, demonstrating superior progression-free survival versus lenalidomide-dexamethasone alone with sustained benefit at extended follow-up. However, patients with severe renal impairment at diagnosis — a high-risk subgroup with significant early morbidity — were historically excluded from pivotal trial populations, creating a clinically meaningful evidence gap.

Emerging real-world data indicate that frontline DRd is feasible and clinically meaningful in transplant-ineligible newly diagnosed myeloma patients with severely impaired renal function (eGFR ≤30 mL/min/1.73 m²). Retrospective series report overall hematologic response rates exceeding 80%, with complete renal responses in approximately 40% of patients — correlating with deeper hematologic responses and significantly prolonged progression-free survival. These findings challenge historical reluctance to deploy full-intensity anti-CD38-based immunotherapy in renally compromised patients and suggest that achieving deep hematologic remission may itself represent the most effective renoprotective strategy. Anti-CD38 monoclonal antibodies do not require dose adjustment for renal impairment, further supporting their use in this population. The evidence shifts the clinical calculus toward earlier, more aggressive treatment rather than sequential watchful adaptation in renally impaired patients.

How do you approach frontline treatment selection in transplant-ineligible newly diagnosed myeloma patients with severe renal impairment, and what parameters guide your decision to initiate anti-CD38-based combination therapy?

What role do depth of hematologic response and early renal recovery play in your prognostic assessment and maintenance planning, and how do you monitor both parameters concurrently in this population?