In newly diagnosed multiple myeloma patients eligible for transplant, combining isatuximab with lenalidomide, bortezomib, and dexamethasone (Isa-RVd) significantly increased minimal residual disease negativity compared to RVd alone. This phase III trial, GMMG-HD7, demonstrated that Isa-RVd induction followed by maintenance therapy prolonged progression-free survival (PFS) with a hazard ratio of 0.70 (95% CI 0.52-0.94, p=0.0184). Subgroup analyses confirmed consistent benefits across various baseline characteristics, highlighting the potential of Isa-RVd in improving outcomes in this patient population.

Key Points:

• Addition of isatuximab to RVd regimen in transplant-eligible NDMM patients showed significantly improved PFS compared to RVd alone.
• Isa-RVd induction achieved MRD negativity in 50% of patients vs. 36% with RVd (p<0.001).
• Trial enrolled 662 patients with 660 in intention-to-treat analysis (Isa-RVd: 331, RVd: 329).
• Median follow-up was 47 months; 3-year PFS rates were 83% (Isa-RVd) vs. 75% (RVd).
• PFS benefit with Isa-RVd was consistent across R-ISS stages, cytogenetic risk groups, and performance statuses.
• Maintenance with lenalidomide or Isa+lenalidomide post-transplantation showed sustained PFS benefits.
• Multivariable analysis confirmed a HR of 0.64 (95% CI 0.47-0.86, p=0.004) for PFS with Isa-RVd.
• OS data were immature, with 3-year rates of 88% (Isa-RVd) vs. 89% (RVd).
• Isa-RVd induction therapy was well-tolerated with manageable toxicity profiles.
• Ongoing trial will assess Isa in combination with lenalidomide for maintenance therapy efficacy.

Authors:
Hartmut Goldschmidt, MD; Uta Bertsch, MD; Ema Pozek; Axel Benner; Roland Fenk, MD, PhD; Britta Besemer, MD; Christine Hanoun; Roland Schroers, MD; Ivana von Metzler, MD; Mathias Hänel, MD; Christoph Mann, MD; Lisa Leypoldt, MD; Bernhard Heilmeier; Stefanie Huhn, PhD; Sabine Vogel, PhD; Michael Hundemer, MD; Christof Scheid, MD; Igor Wolfgang Blau, MD, PhD; Steffen Luntz, MD; Tobias A.W. Holderried, MD; Karolin Trautmann-Grill; Deniz Gezer, MD; Maika Klaiber-Hakimi; Martin Mueller, MD; Evgenii Shumilov; Wolfgang Knauf, MD; Christian Sebastian Michel, MD; Thomas Geer, MD; Hendrik Riesenberg; Christoph Lutz; Marc-Steffen Raab; Martin Hoffmann; Katja C. Weisel, MD; Hans Salwender, MD; Elias K. Mai, MD