Isa-VRd Improves Quality of Life, Prolongs PFS, Increases Likelihood of MRD Negativity in Patients With NDMM

Adding isatuximab-irfc (Isa, Sarclisa; Sanofi) to bortezomib, lenalidomide, and dexamethasone (Isa-VRd) was shown to significantly improve the likelihood of achieving minimal residual disease (MRD) negativity and prolong progression-free survival (PFS) in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The data, which were presented at the 67^th American Society of Hematology (ASH) Annual Meeting and Exposition, emphasize the favorable benefit-risk profile and value of the quadruplet regimen in this patient population.¹

The Phase 3 GMMG-HD7 Clinical Trial (NCT03617731)

The findings are from the prospective, multicenter, randomized, parallel group, open, phase 3 GMMG-HD7 clinical trial (NCT03617731).² A total of 662 patients were randomly assigned to receive either Isa-RVd (n = 331) or RVd (n = 329) during the induction period, followed by single or tandem autologous stem cell transplantation (ASCT), then were randomly assigned again to receive maintenance therapy with Isa-lenalidomide or lenalidomide alone.^1,2

Patient-reported outcomes (PROs) were recorded using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30), the EORTC QLQ Multiple Myeloma Module 20-item (MY20), and the EuroQol 5-dimensional (EQ-5D-5L) visual analog scale (VAS) at baseline, after induction, 60 to 90 days following ASCT, and at the end of treatment. Additionally, prespecified analyses were conducted in the intent-to-treat population; mixed model repeated measures (MMRM) analyzed the mean change from baseline to post-ASCT, and time to first deterioration (TTFD) and time to first improvement (TTFI) were assessed using Kaplan-Meier methods and Cox proportional hazard models.^1,2

Quadruplet Regimen Demonstrates Improved Likelihood of Achieving MRD, Prolonging PFS

The data showed that PRO completion rates were high across time points in both arms (≥90% at baseline, ≥87% after induction, and ≥92% 60–90 days post-ASCT). At baseline, patients in both arms reported similar functioning and symptom burden, QLQ-C30 Global Health Status (GHS/QoL), and EQ-5D-5L VAS.¹

Patients receiving Isa-RVd overall reported a statistically significant reduction in fatigue compared with those receiving RVd (overall mean difference in LS mean change from baseline: –4.02 [95% CI –7.68, -0.37]; p = .0312). Additionally, the median TTFD in fatigue was longer in the Isa-RVd arm than in RVd (8.48 months vs 5.22 months; HR = 0.78; p = .0340), whereas median TTFI was shorter for Isa-RVd (8.84 months vs 10.05 months; HR = 1.26; p = .0611).¹

Notably, clinically meaningful reduction in pain occurred in both treatment arms, with Isa-RVd showing a numerically greater reduction (overall mean difference in LS mean change from baseline: –3.39 [95% CI –7.43, 0.64]; p = .0991). Median TTFD in pain was 12.62 and 12.16 months for Isa-RVd and RVd, respectively (HR = 0.83; p = .2336), whereas median TTFI was 5.06 and 5.26 months for these respective groups (HR = 1.18; p = .1393). There was no clinically meaningful deterioration in other symptom scales observed in either arm, the investigators reported.¹

Further, both Isa-RVd and RVd demonstrated small improvement in physical functioning (LS mean change from baseline: 4.95 vs 3.91; p = .5189) and a clinically meaningful improvement in emotional functioning (LS mean change: 13.27 vs 12.94; p = .8380). There were no notable differences between arms observed for the other functional scales.¹

Both treatments showed clinically meaningful improvement in future perspective, as measured by MY20 following the induction period and ASCT. The overall difference between arms significantly favored Isa-RVd over RVd (overall mean difference in LS mean change from baseline: +5.64 [95% CI 2.15, 9.13], p = .0016). Each arm demonstrated clinically meaningful improvement in QLQ-C30 GHS/QoL after ASCT, with no statistically significant difference between the treatment groups (Isa-RVd: 10.17; RVd: 9.22; p = .5197). Similarly, patients in both treatment arms experienced a clinically meaningful improvement in EQ-5D-5L VAS following ASCT, with a numerical trend in favor of Isa-RVd (overall mean difference in LS mean change from baseline: +1.47 [95% CI –1.28, 4.21], p = .2939).¹

REFERENCES

1. Mai EK, Bertsch U, Fenk R, et al. Health-related quality of life (HRQoL) in patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation and treated with isatuximab, lenalidomide, bortezomib, and dexamethasone (Isa-RVd) versus rvd alone: Results from part 1 of the GMMG-HD7 study. Blood. 2025;146:2263. doi:10.1182/blood-2025-2263

2. Trial on the Effect of Isatuximab to Lenalidomide/​Bortezomib/​Dexamethasone (RVd) Induction and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma (GMMG HD7). ClinicalTrials.gov identifier: NCT03617731. Updated January 24, 2025. Accessed December 9, 2025. https://www.clinicaltrials.gov/study/NCT03617731