CEPHEUS Trial: Efficacy in Transplant-Ineligible Patients
Panelists discuss updated American Society of Clinical Oncology (ASCO) data showing that 4-drug regimens significantly improve outcomes even in patients with transplant-ineligible multiple myeloma, with real-world dose modifications enabling broader use while maintaining efficacy and tolerability.
Updated analysis from this year's ASCO meeting reinforced the benefits of using a 4-drug regimen in transplant-ineligible multiple myeloma patients. While the original study included both transplant-eligible and transplant-deferred individuals, this subgroup analysis focused solely on those deemed truly ineligible. Across key efficacy end points— minimal residual disease (MRD) negativity, sustained MRD response, complete response rates, and both progression-free and overall survival—the 4-drug combination significantly outperformed the 3-drug regimen. Importantly, even within this more vulnerable population, the enhanced outcomes were consistent, suggesting that the benefits of the CD38 antibody-based quadruplet extend beyond fitter patients.
These findings help settle concerns that prior results may have been skewed by the inclusion of healthier deferred-transplant patients. Kaplan-Meier curves for this transplant-ineligible subgroup mirrored those of the broader population, reinforcing the regimen's broad applicability. While high-risk cytogenetic subgroups continued to show more modest gains, most other clinical and genomic subsets demonstrated meaningful improvements in depth and durability of response, reaffirming the role of deeper remissions as a proxy for long-term benefit.
In clinical practice, adapting this regimen for older or frailer patients often involves strategic dose modifications. Many providers use a modified, more tolerable version often referred to informally as Dara-RVD lite. This typically includes a reduced dose of lenalidomide (eg, 15 mg instead of 25 mg), weekly instead of twice-weekly bortezomib, and early tapering or elimination of dexamethasone. Such adjustments maintain efficacy while minimizing toxicities such as peripheral neuropathy and steroid-related adverse effects. This real-world approach ensures that even less robust patients can safely access the benefits of a 4-drug regimen, highlighting the importance of flexibility and personalization in multiple myeloma treatment.
