Updates to Management of Multiple Myeloma

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Natalie S. Callander
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Patricia A. Mangan
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Shaji K. Kumar
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In transplant-eligible patients with newly diagnosed multiple myeloma, quadruplet treatment regimens incorporating an anti-CD38 antibody, followed by autologous stem cell transplant and lenalidomide maintenance, represent the new standard of care, offering improved depth of response and progression-free survival. Transplant-ineligible patients also benefit from anti-CD38 combinations, and quadruplets are showing activity. Management of high-risk disease involves intensified approaches, potentially including early transplant and multidrug maintenance, aiming for sustained measurable residual disease–negative status. In the relapsed/refractory setting, treatment selection depends on prior therapies and patient factors, with effective options including anti-CD38/proteasome inhibitor combinations and anti-CD38/immunomodulatory combinations. For patients with triple-class refractory disease, cellular therapies and T-cell–engaging bispecific antibodies have demonstrated significant efficacy, albeit with unique toxicity profiles requiring specialized management. Emerging therapies, such as cereblon E3 ligase modulators, and targeted agents such as venetoclax offer additional options. Comprehensive supportive care remains crucial throughout treatment.

Disclosures: Dr. Kumar has disclosed receiving grant/research support from AbbVie Inc., Amgen Inc., Bristol Myers Squibb, CARsgen Therapeutics, GSK plc, Janssen Pharmaceutica Products, LP, Oricell Therapeutics, Regeneron Pharmaceuticals, Inc., Roche Laboratories, Inc., Sanofi-Aventis U.S., and Takeda Pharmaceuticals North America, Inc.; receiving consulting fees from Moderna, Inc.; and serving as a scientific advisor for AbbVie Inc., Amgen Inc., Bristol Myers Squibb, GSK plc, Janssen Pharmaceutica Products, LP, Regeneron Pharmaceuticals, Inc., Roche Laboratories, Inc., Sanofi-Aventis U.S., and Takeda Pharmaceuticals North America, Inc. The remaining presenters have disclosed no relevant financial relationships.

Correspondence: Natalie S. Callander, MD, Carbone Cancer Center – University of Wisconsin–Madison, 600 Highland Avenue, Madison, WI 53792. Email: nsc@medicine.wisc.edu;
Patricia A. Mangan, MSN, RN, APRN-BC, CRNP, Abramson Cancer Center at the University of Pennsylvania, West Pavilion, 3400 Civic Center Boulevard, 2nd Floor, Philadelphia, PA 19104. Email: patricia.mangan@pennmedicine.upenn.edu; and
Shaji K. Kumar, MD, Mayo Clinic Comprehensive Cancer Center, 200 First Street SW, Rochester, MN 55905. Email: kumar.shaji@mayo.edu
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