Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma: Final Part 1 Analysis of the GMMG-HD7 Trial
Authors: Mai Elias K. , Bertsch Uta , Pozek Ema , Fenk Roland , Besemer Britta , Hanoun Christine , Schroers Roland , von Metzler Ivana , Hänel Mathias , Mann Christoph , Leypoldt Lisa B. , Heilmeier Bernhard , Huhn Stefanie , Vogel Sabine K. , Hundemer Michael , Scheid Christof , Blau Igor W. , Luntz Steffen , Weinhold Niels , Tichy Diana , Holderried Tobias A.W. , Trautmann-Grill Karolin , Gezer Deniz , Klaiber-Hakimi Maika , Müller Martin , Shumilov Evgenii , Knauf Wolfgang , Michel Christian S. , Geer Thomas , Riesenberg Hendrik , Lutz Christoph , Raab Marc S. , Benner Axel , Hoffmann Martin , Weisel Katja C. , Salwender Hans J. , Goldschmidt Hartmut ,   for the German-Speaking Myeloma Multicenter Group (GMMG) HD7 Investigators, Ahlborn Miriam , Behringer Joachim , Bernhard Helga , Besemer Britta , Bittenbring Jörg , Blau Igor Wolfgang , Bolling Claus , Boquoi Amelie , Debatin Daniel , Egerer Gerlinde , Fenk Roland , Ferstl Barbara , Fronhoffs Stefan , Gaska Tobias , Geer Thomas , Gezer Deniz , Goldschmidt Hartmut , Görner Martin , Graeven Ullrich , Hänel Mathias , Heilmeier Bernhard , Heinsch Michael , Hoffmann Martin , Holderried Tobias A.W. , Hopfer Olaf , Janjetovic Snjezana , Klaiber-Hakimi Maika , Klausmann Martine , Klein Stefan , Knauf Wolfgang , Ko Yon-Dschun , Kraemer Doris Maria , Kropff Martin , La Rosée Paul , Mahlberg Rolf , Mann Christoph , Martens Uwe , von Metzler Ivana , Michel Christian , Müller Martin , Pönisch Wolfram , Reimer Peter , Riechel Claudia , Ringhoffer Mark , Rummel Mathias , Runde Volker , Salwender Hans Jürgen , Schaich Markus , Scheid Christoph , Schmidt-Hieber Martin , Schöndube Daniel , Schroers Roland , Schütte Hans-Joachim , Shumilov Evgenii , Staib Peter , Strumberg Dirk , Tischler Hans-Joachim , Trautmann-Grill Karolin , Verbeek Walter , Weide Rudolf , Weidmann Eckhart , Weisel Katja , de Wit Maike , Bernhardt Christiane , Fietz Thomas , Grassinger Jochen , Köchling Georg , Neise Michael , Schmitt Stefan , Steiniger Heike , Tschechne Barbara , Whitlock Bettina , Zaiß Matthias , Ziske Carsten 
Published: December 2024

Previously, addition of isatuximab (Isa) to standard-of-care lenalidomide-bortezomib-dexamethasone (RVd) in transplant-eligible patients with newly diagnosed multiple myeloma in the GMMG-HD7 trial (ClinicalTrials.gov identifier:
NCT03617731
) resulted in a significant increase of minimal residual disease negativity (MRD–) rates after induction therapy. A total of 662 patients were randomly assigned to receive induction therapy with Isa-RVd (n = 331) or RVd (n = 329), followed by single or tandem autologous stem-cell transplant and second random assignment to maintenance with lenalidomide alone or Isa-lenalidomide. We report updated results for part 1 from first random assignment to post-transplant. As of January 31, 2024, MRD– rates continued to deepen after transplant (66% Isa-RVd
v
48% RVd). Isa-RVd induction therapy significantly prolonged progression-free survival (PFS) compared with RVd regardless of maintenance therapy (hazard ratio, 0.70 [95% CI, 0.52 to 0.95];
P
= .0184). Weighted risk set estimator analysis accounting for second random assignment followed by maintenance with only lenalidomide confirmed a statistically significant benefit for Isa-RVd followed by lenalidomide maintenance versus RVd followed by lenalidomide maintenance (stratified weighted log-rank test
P
= .016). In conclusion, after 18-week induction therapy followed by transplant without consolidation therapy, adding Isa to RVd resulted in a significant PFS benefit, regardless of maintenance strategy.