San MIguel ImS

“The results of this study demonstrate that to achieve MRD negativity is not only associated with a significant benefit in progression-free survival, but [it is] associated with less treatment adverse [effects] and very similar patient-reported outcomes.”

Jesús San Miguel, MD, PhD, professor of hematology and director of clinical and translational medicine at Clínica Universidad de Navarra, discussed outcomes from the phase 3 PERSEUS (NCT03710603) and CEPHEUS (NCT03652064) trials regarding the prognostic significance of minimal residual disease (MRD) negativity with a complete response (CR) or better, and its relationship to safety and patient-reported outcomes (PROs) in patients with newly diagnosed multiple myeloma.

San Miguel emphasized that MRD negativity with a CR or better, when achieved in the context of the regimen of daratumumab (Darzalex), bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (D-VRd) evaluated during the 2 studies, was associated with prolonged progression-free survival and more favorable safety outcomes without detriment to health-related quality of life (HRQOL). This observation reinforces the role of MRD negativity as a clinically meaningful endpoint in newly diagnosed multiple myeloma.

Exposure-adjusted analyses from both trials demonstrated that patients who achieved MRD negativity experienced lower rates of treatment-emergent adverse effects (TEAEs), including grade 3/4 toxicities, compared with MRD-positive patients. Specifically, in PERSEUS, MRD-negative patients had lower exposure-adjusted rates of serious TEAEs, discontinuations, and grade 3/4 neutropenia compared with their MRD-positive counterparts. Similar trends were observed in CEPHEUS, underscoring the consistency of these findings across independent datasets. Importantly, no excess safety concerns were observed in MRD-negative patients despite their longer treatment exposure.

Regarding PROs, both PERSEUS and CEPHEUS evaluated global health status using the EORTC QLQ-C30 instrument. Patients in the D-VRd arms who achieved MRD negativity reported PRO scores comparable with those of MRD-positive patients, with no evidence of deterioration in HRQOL despite deeper and more durable responses. These findings suggest that the pursuit of MRD negativity does not compromise QOL and may align with improved tolerability.

San Miguel noted that this convergence of efficacy, safety, and patient experience provides reassurance for clinicians that striving for MRD negativity should remain a primary therapeutic goal in newly diagnosed multiple myeloma.

Videos

Jesús San Miguel, MD, PhD, discusses patient-reported outcomes and safety for patients with newly diagnosed multiple myeloma who achieved MRD negativity and a CR or better.

Dr San Miguel on the Association Between MRD-Negative CR and PFS/Safety in Newly Diagnosed Myeloma

Jesus San Miguel, MD, PhD, professor of Hematology, medical director of the Clínica Universidad de Navarra, Universidad de Navarra, Pamplona, Spain, discusses the Keynote-023 study, which examined pembrolizumab in combination with lenalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.

This open-label, phase I, multicenter, nonrandomized, dose-escalation trial evaluated the safety, tolerability, and efficacy of pembrolizumab in combination with lenalidomide and low-dose dexamethasone in these patients, who were heavily pretreated with more than three prior lines of therapy, San Miguel says. More than 95% of patients were treated with lenalidomide and bortezomib, 25% previously received carfilzomib and pomalidomide; 80% of patients underwent autologous stem cell transplantation, and 75% of patients were lenalidomide-refractory.

Researchers aimed to create an immune effect to enhance the capacity of the immune system to control tumor cells by adding pembrolizumabto the doublet, San Miguel explains. This triplet therapy was associated with a tolerable safety profile, but San Miguel cautions the data is preliminary.

View more from the 2015 ASH Annual Meeting

Jesus San Miguel, MD, PhD, professor of Hematology, medical director of the ClÃ­nica Universidad de Navarra, Universidad de Navarra, Pamplona, Spain, discusses the Keynote-023 study, which examined pembrolizumab in combination with lenalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.


Jesus San Miguel, MD, PhD

Articles

Dr San Miguel on the Association Between MRD-Negative CR and PFS/Safety in Newly Diagnosed Myeloma

Dr. San Miguel on Pembrolizumab With Lenalidomide/ Dexamethasone in Multiple Myeloma