-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

463 Addition of Isatuximab to Lenalidomide, Bortezomib and Dexamethasone As Induction Therapy for Newly-Diagnosed, Transplant-Eligible Multiple Myeloma Patients: The Phase III GMMG-HD7 Trial

Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Myeloma and Plasma Cell Dyscrasias: Clinical-Prospective Therapeutic Trials; treatment of NDMM and amyloidosis patients
Hematology Disease Topics & Pathways:
Clinical Trials, Workforce, Plasma Cell Disorders, Diseases, Lymphoid Malignancies
Sunday, December 12, 2021: 12:00 PM

Hartmut Goldschmidt1,2,3, Elias K Mai, MD4*, Eva Nievergall, PhD3*, Roland Fenk, MD5*, Uta Bertsch, MD2,3*, Diana Tichy, PhD6*, Britta Besemer, MD7*, Jan Dürig, MD8*, Roland Schroers, MD9*, Ivana v. Metzler, MD10*, Mathias Haenel, MD11*, Christoph Mann, MD12*, Anne-Marie Asemissen, MD13*, Bernhard Heilmeier14*, Stefanie Huhn, PhD3*, Katharina Kriegsmann, MD3*, Niels Weinhold, PhD3*, Steffen P. Luntz, MD15*, Tobias A. W. Holderried, MD16*, Karolin Trautmann-Grill, MD17*, Deniz Gezer, MD18*, Maika Klaiber-Hakimi, MD19*, Martin Mueller, MD20*, Cyrus Khandanpour, PD, MD21, Wolfgang Knauf, MD, PhD22, Markus Munder, MD23*, Thomas Geer, MD24*, Hendrik Riesenberg, MD25*, Joerg Thomalla, MD26*, Martin Hoffmann, MD27*, Marc-Steffen Raab28*, Hans Salwender, MD29* and Katja Weisel13*

1University Hospital Heidelberg and National Center of Tumor Diseases, Heidelberg, Germany
2National Center for Tumor Diseases (NCT), Heidelberg, Germany
3Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany
4Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
5Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Duesseldorf, Germany
6Division of Biostatistics, German Cancer Research Center Heidelberg, Heidelberg, Germany
7Medical Clinic II, University Tuebingen, Tuebingen, Germany
8Department of Hematology, Essen University Hospital, Essen, Germany
9Knappschaftskrankenhaus Bochum, Bochum, Germany
10Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
11Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
12Department of Hematology, Oncology, Immunology, University Marburg, Marburg, Germany
13Department of Oncology, Hematology and BMT, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
14Clinic for Oncology and Hematology, Hospital Barmherzige Brueder Regensburg, Regensburg, Germany
15Coordination Centre for Clinical Trials (KKS), University Hospital Heidelberg, Heidelberg, Germany
16Department of Hematology, Oncology, Immunoncology and Rheumatology / Internal Medicine III, University Hospital Bonn, Bonn, Germany
17Medical Clinic I, University Hospital Dresden, Dresden, Germany
18Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
19Marien Hospital Duesseldorf, Duesseldorf, Germany
20Clinic for Hematology, Oncology and Immunology, KRH Hospital Siloah, Hannover, Germany
21Med. Department A, University Hospital Muenster, Muenster, Germany
22Center Hematology/Oncology Bethanien, Private Practice, Frankfurt, Germany
23Third Department of Medicine, University Medicine Mainz of Johannes Gutenberg University Mainz, Mainz, Germany
24Medical Clinic III, Diakonie Hospital, Schwaebisch Hall, Germany
25Hematology/Oncology Center Bielefeld, Bielefeld, Germany
26Hematology / Oncology Center Koblenz, Koblenz, Germany
27Ludwigshafen Clinical Center, Medical Clinic A, Ludwigshafen Hospital, Ludwigshafen, Germany
28Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
29Asklepios Tumorzentrum Hamburg, AK Altona and AK St. Georg, Hamburg, Germany

Background: In newly-diagnosed multiple myeloma (NDMM), lenalidomide/bortezomib/dexamethasone (RVd) is one of the most widely used combination regimens. Anti-CD38 monoclonal antibodies (CD38-moAb) increase efficacy when added to standard-of-care regimens. Here we present the first primary endpoint of the randomized, open-label, multicenter, phase III GMMG-HD7 trial, comparing RVd without (arm IA) or with the CD38-moAb isatuximab (Isa, arm IB) with regard to the rate of minimal residual disease (MRD) negativity after induction therapy in patients with transplant-eligible NDMM.

Patients and Methods: Patients with transplant-eligible NDMM at 67 sites in Germany were equally randomized to receive three 42-day cycles of RVd (lenalidomide 25 mg/d p.o., d1–14 and d22-35; bortezomib 1.3 mg/m2 s.c. d1, 4, 8, 11, 22, 25, 29, 32; dexamethasone 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33) in both arms. Isa was added to arm IB only (10 mg/kg i.v., cycle 1: d 1, 8, 15, 22, 29; cycles 2-3: d 1, 15, 29). Randomization for induction was stratified according to revised International Staging System (R-ISS). Primary endpoint of the trial was MRD negativity assessed by next-generation flow (NGF, cut off 1x10-5) after induction. Secondary endpoints included rates of complete response (CR) after induction and safety. Data cut-off for the present analysis was April 2021.

Results: Between 10/2018 and 09/2020, 662 patients were included in the trial. 660 patients were eligible for intention-to-treat analysis and 658 patients started induction (RVd: 329/328 and Isa-RVd: 331/330). Median age was 58 (range 26–70) years and baseline characteristics were well balanced between treatment arms. On induction, 35 (10.6%) and 18 (5.4%) patients discontinued treatment in the RVd vs. Isa-RVd arms (p=0.02). Among these, 8 (2.4%, RVd) vs. 7 (2.1%, Isa-RVd) patients discontinued induction due to adverse events (AE). 293 (89.1%) vs. 312 (94.3%) patients in the RVd vs. Isa-RVd arms continued further study treatment after induction.

MRD negativity rates after induction were 35.6% vs. 50.1% (odds ratio [OR]=1.83, 95% confidence interval [95% CI]: 1.34-2.51, p<0.001) for RVd vs. Isa-RVd, respectively. On multivariate analyses including treatment arm, R-ISS, performance status, renal impairment, age and sex, treatment with Isa-RVd (vs. RVd) remained the only significant predictor for increased MRD negativity after induction (OR=1.82, 95% CI: 1.33-2.49, p<0.001). While the rates of CR after induction did not yet differ between the RVd vs. Isa-RVd arms (21.6% vs. 24.2%, p=0.46), the rate of very good partial response or better (≥VGPR) was significantly higher in the Isa-RVd arm (60.5% vs. 77.3%, p<0.001). The rates of progressive disease were 4.0% (RVd) vs. 1.5% (Isa-RVd).

At least one AE (grade ≥3) on induction occurred in 61.3% (RVd) and 63.6% (Isa-RVd) of patients (p=0.57). Most common AE (grade ≥3) by system organ class (SOC) for RVd vs. Isa-RVd were: “investigations”: 23.5% vs. 23.9% (p=0.93), “blood and lymphatic system disorders”: 16.8% vs. 25.8% (p=0.006), „infections and infestations“: 10.4% vs. 13.0% (p=0.33) and “nervous system disorders“: 10.1% vs. 8.5% (p=0.50). Rates of serious AE (SAE, any grade) on induction were similar between RVd and Isa-RVd (36.3% vs. 34.8%, p=0.75). Eight (RVd) and four (Isa-RVd) patients died during induction.

Conclusions: The GMMG-HD7 trial met its primary endpoint. To the best of our knowledge this is the first phase III trial to demonstrate superiority of MRD negativity rates after induction by adding a CD38-moAb to RVd. There were no increased rates of SAE or early discontinuation in patients treated with Isa-RVd compared to RVd. The trial is ongoing, including analyses post autologous transplantation, which is followed by a second randomization to compare the efficacy of the addition of Isa to lenalidomide maintenance.

Disclosures: Goldschmidt: Takeda: Consultancy, Research Funding; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Adaptive Biotechnology: Consultancy; Incyte: Research Funding; GSK: Honoraria; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Novartis: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding. Mai: Celgene / BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Glaxo Smith Kline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding. Fenk: Takeda: Honoraria; GSK: Honoraria; Amgen: Honoraria; Janssen: Honoraria; BMS/Celgene: Honoraria. Besemer: Takeda: Honoraria; Janssen: Honoraria; GSK: Honoraria. Dürig: Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Schroers: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Takeda: Honoraria. Metzler: Takeda: Consultancy; BMS: Consultancy; GSK: Consultancy; Amgen: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy. Haenel: Takeda: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; GSK: Consultancy; Bayer Vital: Honoraria; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy; Celgene: Consultancy, Honoraria. Mann: Cellgene: Consultancy. Asemissen: GSK: Honoraria; Pfizer: Honoraria; Celgene BMS: Honoraria. Heilmeier: Sanofi-Aventis Dtld. GmbH: Consultancy. Kriegsmann: Sanofi: Honoraria. Weinhold: Sanofi: Honoraria. Holderried: Amgen: Speakers Bureau; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Eurocept Pharmaceuticals: Other: Travel support; MSD: Speakers Bureau; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Other: Travel support; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Travel support; Therakos: Other: Travel support; Daiichi Sankyo: Other: travel support; Medac: Other: Travel support; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Trautmann-Grill: Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Gezer: Amgen: Consultancy, Other: Invited Speaker; Takeda: Consultancy, Other: Invited Speaker; BMS: Consultancy, Other: Invited Speaker; Celgene: Consultancy, Other: Invited Speaker. Khandanpour: GSK: Honoraria; Takeda: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria, Research Funding; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; BMS/Celgene: Honoraria. Knauf: Amgen: Honoraria; Abbvie: Honoraria; Beigene: Consultancy, Honoraria; BMS: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Honoraria; AstraZeneca: Consultancy, Honoraria. Munder: GSK: Consultancy; Amgen: Honoraria; Sanofi: Consultancy; Takeda: Consultancy, Honoraria; Abbvie: Consultancy; BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Incyte: Research Funding. Hoffmann: Sanofi-Aventis: Consultancy. Raab: Roche: Consultancy; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Salwender: GlaxoSmithKline: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Chugai: Honoraria; Oncopeptides: Honoraria; Takeda: Honoraria; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; AbbVie: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Janssen-Cilag: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Bristol-Myers Squibb/Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Pfizer: Honoraria. Weisel: Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria.

OffLabel Disclosure: Isatuximab prior to ASCT in NDMM

Previous Abstract | Next Abstract >>
*signifies non-member of ASH