Daratumumab regimen confers health-related quality of life benefit in multiple myeloma
NEW ORLEANS — Adding daratumumab to bortezomib, lenalidomide and dexamethasone led to improved health-related quality of life for transplant-eligible patients with newly diagnosed multiple myeloma, study results showed.
The findings, presented at ASH Annual Meeting and Exposition, also showed reduced pain symptoms with the addition of daratumumab (Darzalex, Janssen), an anti-CD38 monoclonal antibody, to the standard induction/consolidation regimen with autologous hematopoietic stem cell transplant (HSCT) and lenalidomide (Revlimid, Bristol Myers Squibb) maintenance.
“Overall, these findings further support the benefits of front-line daratumumab as part of a quadruplet therapy with no detriment to health-related quality of life,” Rebecca Silbermann, MD, MMS, associate professor of medicine in the division of hematology/medical oncology at Oregon Health & Science University, said during a presentation.
Background
The multicenter, randomized phase 2 GRIFFIN study evaluated the combination of daratumumab, bortezomib (Velcade, Takeda), lenalidomide and dexamethasone (D-RVd) vs. bortezomib, lenalidomide and dexamethasone (RVd) among transplant-eligible adults with newly diagnosed multiple myeloma. Results of a final analysis showed a clinically meaningful PFS benefit with the daratumumab regimen (HR = 0.45; 95% CI, 0.21-0.95), and researchers observed rising rates of response and minimal residual disease negativity during the study with no new safety signals.
Slibermann and colleagues looked at patient-reported outcomes (PROs) with 1 year of follow-up (median, 49.6 months) after maintenance therapy.
Methodology
The researchers used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30), EORTC QLQ Multiple Myeloma Module 20-item (EORTC QLQ-MY20) and EuroQol 5-dimensional (EQ-5D-5L) descriptive system to assess PROs at baseline on day 1 of the first, second, third and fifth treatment cycles, on day 21 of the fourth cycle, after HSCT consolidation, and at months 6, 12, 18 and 24 of maintenance.
The study included 207 patients randomly assigned to the D-RVd (n = 104) or RVd (n = 103) regimen. PRO compliance rates exceeded 81% at baseline but decreased to 49% in the D-RVd group and 45% in the RVd group at month 24 of maintenance. The groups had similar mean PRO scores at baseline.
Key findings
Results showed improvements in global health status in both the D-RVd and RVd groups from baseline to maintenance month 24 (least squares [LS] mean change, 13.6 vs. 9.4) and physical functioning (LS mean change, 22 vs. 12.6).
Patients in both groups also demonstrated a meaningful reduction in pain symptoms, but researchers observed large decreases favoring D-RVd after HSCT consolidation and during maintenance (LS mean change, 30.4 vs. 19.7). The D-RVd group also had a greater reduction in fatigue symptoms at maintenance month 24 (LS mean change, 19.1 vs. 13.1).
Reductions in disease symptoms favored D-RVd vs. RVd at multiple time points (LS mean change, 15.5 vs. 8.2), and both groups had similar increases in future perspective scores.
Silbermann noted the noticeably longer median time to first worsening of global health status in the D-RVd group. “When treated with D-RVd, it took an additional 30 months before global health status worsening was reported vs. RVd,” she said.
Clinical implications
The results add to mounting evidence of the benefits of the daratumumab regimen for transplant-eligible patients with multiple myeloma, Silbermann said.
“These results are supported further by data from the final analysis of the GRIFFIN trial, presented at this conference, confirming the improved PFS and MRD [minimal residual disease]-negativity rates among high-risk subgroups, as well as continued clinical benefit of D-RVd vs. RVd among Black patients,” she said.
References:
- Sborov D, et al. Abstract OAB-057. Presented at: International Myeloma Society Annual Meeting; Aug. 25-27, 2022; Los Angeles.
- Silbermann R, et al. Abstract 473. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
Perspective
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Multiple myeloma is the second most common hematologic malignancy and, despite remarkable progress, remains incurable for the majority of patients.
For several years, induction chemotherapy using RVd has been the standard of care for patients with newly diagnosed multiple myeloma who are eligible for autologous HSCT.
The GRIFFIN trial demonstrated that adding daratumumab to the RVd backbone during induction and consolidation significantly improved the rate of post-consolidation stringent complete response compared with RVd alone. Patients in the daratumumab group also received it after transplant in combination with lenalidomide maintenance. With longer follow-up, the responses continued to deepen, and patients in the daratumumab group had double the rate of MRD negativity and triple the rate of sustained MRD negativity at the 10-5 threshold compared with the non-daratumumab group. Although infections and neutropenia were more common in the daratumumab group, incidence of grade 3 and grade 4 infections were similar.
Silberman presented patient-reported outcomes of the GRIFFIN study at the final study analysis, after over 4 years of median follow-up. The results demonstrated that the addition of daratumumab to RVd induction/consolidation, and lenalidomide maintenance led to improvements in health-related quality of life, with a notable reduction in pain symptoms.
Overall, these findings corroborate the benefits of combining daratumumab with RVd, leading to better disease control and improvements in health-related quality of life. Although these promising outcomes support the use of daratumumab-based quadruplet therapy in transplant-eligible patients with newly diagnosed multiple myeloma, one of the caveats of this randomized phase 2 trial is the higher rate of discontinuation in the RVd group. Consequently, a lower percentage of patients in this group underwent autologous HSCT. Accrual to the phase 3 PERSEUS study (NCT03710603) has been completed, and those results are eagerly awaited.
Reference:
Sborov D, et al. Abstract OAB-057. Presented at: International Myeloma Society Annual Meeting; Aug. 25-27, 2022; Los Angeles.
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Silbermann R, et al. Abstract 473. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.