Depth of response to isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: Interim analysis of the GMMG-CONCEPT trial.

Author:

Weisel Katja1,Asemissen Anne Marie2,Besemer Britta3,Haenel Mathias4,Blau Igor W.5,Goerner Martin6,Ko Yon-Dschun7,Dürig Jan8,Staib Peter9,Mann Christoph10,Lutz Raphael11,Munder Markus12,Graeven Ullrich13,Peceny Rudolph14,Salwender Hans15,Zago Manola16,Benner Axel17,Tichy Diana17,Bokemeyer Carsten18,Goldschmidt Hartmut19

Affiliation:

1. University Medical Center of Hamburg-Eppendorf, Hamburg, Germany;

2. Medical Center of Hamburg-Eppendorf, Hamburg, Germany;

3. University Hospital Tuebingen, Tübingen, Germany;

4. Klinik für Innere Medizin III, Klinikum Chemnitz, Chemnitz, Germany;

5. Department of Internal Medicine III, Charité Campus Benjamin Franklin, Berlin, Germany;

6. Klinikum Bielefeld, Bielefeld, Germany;

7. Johanniter Krankarhaus, Bonn, Germany;

8. Universitätsklinikum Essen (AöR), Essen, Germany;

9. St Antonius Hospital, Eschweiler, Germany;

10. University Hospital Marburg, Marburg, Germany;

11. University Hospital Heidelberg, Heidelberg, Germany;

12. University Medical Center of the Johannes Gutenberg-University, Third Department of Medicine, Mainz, Germany;

13. Kliniken Maria Hilf GmbH, Mönchengladbach, Germany;

14. Klinikum Osnabrück GmbH, Osnabrueck, Germany;

15. Asklepios Tumorzentrum Hamburg, AK Altona and AK St Georg, Hamburg, Germany;

16. Center for Clinical Trials, University Hospital of Tuebingen, Tübingen, Germany;

17. Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany;

18. University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

19. University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT), Heidelberg, Germany;

Abstract

8508 Background: High-risk (HR) multiple myeloma (MM) still has a significant impaired prognostic outcome. Addition of CD38 monoclonal antibodies to standard-of-care regimens significantly improved response rates and depth of response in newly diagnosed (ND) and relapsed/refractory MM patients (pts). Here, we report the prespecified end of induction interim analysis (IA) of the investigator-initiated GMMG-CONCEPT trial (NCT03104842), evaluating the quadruplet regimen isatuximab plus carfilzomib, lenalidomide and dexamethasone (Isa-KRd) in HR NDMM pts. Methods: 153 pts with HR NDMM are planned to be included into the trial. HR MM is defined by the presence of del17p or t(4;14) or t(14;16) or > 3 copies 1q21 and ISS 2 or 3 stage disease. Pts receive 6 cycles of Isa-KRd induction, 4 cycles of Isa-KRd consolidation and Isa-KR maintenance. Transplant eligible pts (arm A) undergo high-dose therapy. Transplant ineligible pts (arm B) receive 2 additional cycles of Isa-KRd induction. The primary endpoint is MRD negativity measured by next-generation flow after consolidation. This IA reports on overall response rates (ORR) after induction. Additional MRD analysis will be presented. Results: 50 pts (46 arm A, 4 arm B) were included in the IA population for ORR. HR MM was defined by del17p in 52%, t(4;14) in 38%, t(14;16) in 12% and > 3 copies 1q21 in 42%. 39/46 pts in arm A and 4/4 pts in arm B completed induction treatment. ORR was 100%, with 5 pts (10.0%) showing partial response (PR), 22 (44.0%; including 4 in arm B) very good partial response (VGPR) and 23 (46.0 %) complete response (CR). Median stem cell yield was 6.6 × 106CD34+ cells/kg. Grade 3/4 treatment-emergent adverse events (≥ 10%) with Isa-KRd included neutropenia (34.0%), leukopenia (26.0%) and thrombocytopenia (14.0%). Main non-hematologic toxicities grade 3/4 were hypertension (12.0%) and infection (8.0%). Conclusions: To the best of our knowledge, we report for the first time on a trial investigating solely HR NDMM and Isa-KRd quadruplet treatment. Isa-KRd induction induces deep responses in HR MM pts. The overall safety profile of Isa-KRd is expected and consistent with previous reports. The study is ongoing, with pts continuing to be included. Clinical trial information: 03104842 .

Funder

Sanofi, Celgene, Amgen

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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