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(s): ,
Katja Weisel
Affiliations:
University Medical Center of Hamburg-Eppendorf,Hamburg,Germany
,
Anne Marie Asemissen
Affiliations:
University Medical Center of Hamburg-Eppendorf,Hamburg,Germany
,
Britta Besemer
Affiliations:
University of Tuebingen,Tuebingen,Germany
,
Mathias Hänel
Affiliations:
Klinikum Chemnitz,Chemnitz,Germany
,
Wolfgang Blau
Affiliations:
Charité,Berlin,Germany
,
Martin Goerner
Affiliations:
Klinikum Bielefeld,Bielefeld,Germany
,
Yon-Dschun Ko
Affiliations:
Johanniter Kliniken,Bonn,Germany
,
Jan Duerig
Affiliations:
University Hospital of Essen,Essen,Germany
,
Peter Staib
Affiliations:
Krankenhaus Eschweiler,Eschweiler,Germany
,
Christoph Mann
Affiliations:
University Hospital of Marburg,Marburg,Germany
,
Raphael Lutz
Affiliations:
University Hospital of Heidelberg,Heidelberg,Germany
,
Markus Munder
Affiliations:
University Hospital of Mainz,Mainz,Germany
,
Ullrich Graeven
Affiliations:
Krankenhaus Mariahilf ,Mönchengladbach,Germany
,
Rudolph Peceny
Affiliations:
Klinikum Osnabrück,Osnabrück,Germany
,
Hans Salwender
Affiliations:
Asklepios Klinik Altona,Hamburg,Germany
,
Manola Zago
Affiliations:
University of Tuebingen,Tuebingen,Germany
,
Axel Benner
Affiliations:
DKFZ,Heidelberg,Germany
,
Diana Tichy
Affiliations:
DKFZ,Heidelberg,Germany
,
Carsten Bokemeyer
Affiliations:
University Medical Center of Hamburg-Eppendorf,Hamburg,Germany
Hartmut Goldschmidt
Affiliations:
University Hospital of Heidelberg,Heidelberg,Germany
EHA Library. Weisel K. 06/12/20; 295024; S204
Katja Weisel
Katja Weisel
Contributions
Abstract

Abstract: S204

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: New insights in the treatment of newly diagnosed multiple myeloma

Background

High-risk multiple myeloma (MM) disease still has an impaired prognostic outcome. Addition of monoclonal anti CD38 antibodies to standard-of-care (SOC) regimens significantly improved response rates, depth of response including minimal residual disease (MRD) negativity, and progression-free survival (PFS) in NDMM and relapsed/refractory MM patients. KRd followed by high-dose therapy (HDT), autologous stem cell transplant (ASCT), and consolidation is an optimized SOC induction treatment for patients with newly-diagnosed (ND)MM. This phase 2 trial (GMMG-CONCEPT; Eudra-CT No 2016-000432-17) evaluated the monoclonal anti CD38 antibody Isatuximab (Isa) plus KRd (Isa-KRd) in NDMM high-risk patients. A 10-pt safety run-in showed no safety concerns.

Aims
Here, we report the results of an exploratory interim analysis (IA) in respect to induction with Isa-KRd in both, transplant-eligible (TE) and non-transplant eligible (TNE) patients.

Methods
The trial was planned to include 153 patients with HR MM defined as presence of del17p or t(4;14) or t(14;16) or > 3 copies 1q21 and ISS 2 or 3 stage disease. Patients should receive 6 cycles of Isa-KRd induction, 4 cycles of Isa-KRd consolidation and Isa-KR maintenance and when eligible to transplantation (arm A) undergo high-dose therapy, whereas ineligible patients (arm B) receive 2 additional cycles of Isa-KRd induction. The primary study endpoint is MRD negativity measured by next-generation flow (NGF) after consolidation. Here we report the results of the planned exploratory IA reports on overall response rates (ORR) after induction and MRD negativity for the first time.

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 patients (10.0%) showing a partial remission (PR), 22 very good partial response (VGPR) (44.0%) and 23 complete remission (CR) (46.0 %). All 4 patients treated in arm B achieved VGPR. MRD analysis was performed in 30 patients achieving at least VGPR. MRD negativity was shown 20/30 patients (67%). Patients in arm A underwent stem cell mobilization. Stem cell yield was 6.6 × 106 CD34+ cells/kg at the median. Safety was analyzed in all 50 patients. Grade 3/4 treatment-related 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%).

Conclusion
To the best of our knowledge, we report for the first time on a trial investigating solely HR NDMM. The 4-drug combination of Isa-KRd was administered for the first time for treatment of MM patients. Isa-KRd induction induces deep responses HR MM patients with a high number of MRD negativity. The overall safety profile of Isa-KRd is consistent with previous reports with anti CD38 antibodies combined with SOC regimens. Stem cell mobilization and ASCT is feasible and will be reported seperately. The study is ongoing, with patients continuing to be included.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Abstract: S204

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: New insights in the treatment of newly diagnosed multiple myeloma

Background

High-risk multiple myeloma (MM) disease still has an impaired prognostic outcome. Addition of monoclonal anti CD38 antibodies to standard-of-care (SOC) regimens significantly improved response rates, depth of response including minimal residual disease (MRD) negativity, and progression-free survival (PFS) in NDMM and relapsed/refractory MM patients. KRd followed by high-dose therapy (HDT), autologous stem cell transplant (ASCT), and consolidation is an optimized SOC induction treatment for patients with newly-diagnosed (ND)MM. This phase 2 trial (GMMG-CONCEPT; Eudra-CT No 2016-000432-17) evaluated the monoclonal anti CD38 antibody Isatuximab (Isa) plus KRd (Isa-KRd) in NDMM high-risk patients. A 10-pt safety run-in showed no safety concerns.

Aims
Here, we report the results of an exploratory interim analysis (IA) in respect to induction with Isa-KRd in both, transplant-eligible (TE) and non-transplant eligible (TNE) patients.

Methods
The trial was planned to include 153 patients with HR MM defined as presence of del17p or t(4;14) or t(14;16) or > 3 copies 1q21 and ISS 2 or 3 stage disease. Patients should receive 6 cycles of Isa-KRd induction, 4 cycles of Isa-KRd consolidation and Isa-KR maintenance and when eligible to transplantation (arm A) undergo high-dose therapy, whereas ineligible patients (arm B) receive 2 additional cycles of Isa-KRd induction. The primary study endpoint is MRD negativity measured by next-generation flow (NGF) after consolidation. Here we report the results of the planned exploratory IA reports on overall response rates (ORR) after induction and MRD negativity for the first time.

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 patients (10.0%) showing a partial remission (PR), 22 very good partial response (VGPR) (44.0%) and 23 complete remission (CR) (46.0 %). All 4 patients treated in arm B achieved VGPR. MRD analysis was performed in 30 patients achieving at least VGPR. MRD negativity was shown 20/30 patients (67%). Patients in arm A underwent stem cell mobilization. Stem cell yield was 6.6 × 106 CD34+ cells/kg at the median. Safety was analyzed in all 50 patients. Grade 3/4 treatment-related 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%).

Conclusion
To the best of our knowledge, we report for the first time on a trial investigating solely HR NDMM. The 4-drug combination of Isa-KRd was administered for the first time for treatment of MM patients. Isa-KRd induction induces deep responses HR MM patients with a high number of MRD negativity. The overall safety profile of Isa-KRd is consistent with previous reports with anti CD38 antibodies combined with SOC regimens. Stem cell mobilization and ASCT is feasible and will be reported seperately. The study is ongoing, with patients continuing to be included.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies