Evaluating First-Line Treatment Options: Quadruplet vs Triplet Regimens and NCCN Guidelines

EP: 1.Treatment Approaches and Goals: Transplant-Eligible vs. Transplant-Ineligible Patients

EP: 2.The Role of ASCT in Frontline Myeloma: Comparative Risks and Benefits with Other Standard Treatment Approaches

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EP: 3.Evaluating First-Line Treatment Options: Quadruplet vs Triplet Regimens and NCCN Guidelines

This segment examines the safety and tolerability profiles of quadruple-therapy regimens compared to triplet regimens in multiple myeloma treatment, addressing key concerns about adding anti-CD38 antibodies to existing treatment protocols. Clinical experience suggests that while there may be theoretical differences in safety profiles, real-world practice shows minimal additional toxicity from quadruplet regimens. The primary adverse effects continue to stem from the traditional 3-drug components (proteasome inhibitors, immunomodulatory drugs, and dexamethasone) rather than the added CD38 antibody.

The anti-CD38 monoclonal antibodies, particularly daratumumab, are described as among the easiest drugs to deliver in multiple myeloma treatment, with infusion reactions being the primary concern during initial doses. This represents a significant improvement over previous quadruple therapy attempts that included drugs with substantial gastrointestinal toxicity. The current CD38-based quadruplet regimens have proven more tolerable and manageable than earlier combination approaches, making them practical for routine clinical use.

NCCN guidelines now recommend 4-drug regimens as standard care for transplant-eligible patients, reflecting the growing confidence in their safety profile and superior efficacy. The expert panel notes that for transplant-eligible patients, there are very few scenarios where quadruplet therapy wouldn’t be appropriate, with subcutaneous injection absorption issues being one of the rare exceptions. The emphasis on “more is more” in multiple myeloma treatment reflects the field’s evolution toward maximizing frontline therapy intensity to achieve optimal long-term outcomes.