Episode 71. Management of Newly Diagnosed Multiple Myeloma with Dr. Vincent Rajkumar

In this episode, Raj, Ashwin, and Eddie sit down with Dr. Vincent Rajkumar — Professor of Medicine at Mayo Clinic and Chair of the ECOG Myeloma Committee — for a clinically focused conversation on newly diagnosed multiple myeloma. Topics span baseline workup, risk stratification, induction selection, transplant timing, MRD-directed decision-making, and maintenance strategy. The episode closes with a discussion of Open Medicine, a new medical education platform, and Dr. Rajkumar's ongoing advocacy on drug pricing reform.

KEY TOPICS DISCUSSED

Baseline workup: 24-hour urine protein: It is important to obtain 24-hour urine protein with electrophoresis and immunofixation in all newly diagnosed patients — not for diagnosis, but to establish a baseline for long-term management and to distinguish M-protein from albuminuria. In patients where an FLC ratio ≥100 is the sole myeloma-defining criterion, a 24-hour urine Bence Jones protein ≥200 mg is part of the diagnostic threshold for treatment initiation.

Myeloma cast nephropathy: when to biopsy: An involved FLC ≥50 mg/dL supports a presumptive diagnosis of cast nephropathy and treatment can begin without a kidney biopsy. Below this threshold — particularly if renal involvement is the sole myeloma-defining event — kidney biopsy is warranted to exclude light chain deposition disease, MPGN, or other unrelated disorders. It warrants aggressive early treatment (Dara-VCD or Dara-VD), starting even before bone marrow results are available when the diagnosis is clinically clear.

Solitary plasmacytoma [with or without minimal bone marrow involvement]: Patients with ~10% clonal plasma cells technically meet criteria for myeloma, but management in this borderline zone warrants shared decision-making. Solitary plasmacytoma as sitting between smoldering myeloma and overt myeloma on the disease spectrum.

Risk stratification: revised IMWG criteria: The new revision aimed to keep the high-risk designation to ≤15–20% of patients. Del 17p alone confers high-risk status. TP53 mutation without del 17p is exceedingly rare and FISH alone captures the vast majority of cases. All other cytogenetic abnormalities (t(4;14), t(14;16), t(14;20), 1q gain, 1p deletion, biallelic 1p) require at least one co-occurring abnormality to define high risk. Elevated β2-microglobulin with normal renal function is retained as a proxy for high tumor burden.

Emergent indications for treatment initiation: The three situations warranting urgent treatment are