EFFECT OF PROLONGED TREATMENT WITH CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE IN RELAPSED AND REFRACTORY MULTIPLE MYELOMA
Author(s): ,
Cécile Gruchet
Affiliations:
CHU Poitiers,Poitiers,France;CHU Poitiers,Poitiers,France
,
Niels Moya
Affiliations:
CHU Poitiers,Poitiers,France
,
Florence Sabirou
Affiliations:
CHU Poitiers,Poitiers,France
,
Anthony Levy
Affiliations:
CHU Poitiers,Poitiers,France
,
Arthur Bobin
Affiliations:
CHU Poitiers,Poitiers,France
,
Hélène Gardeney
Affiliations:
CHU Poitiers,Poitiers,France
,
Laly Nsiala Makunza
Affiliations:
CHU Poitiers,Poitiers,France
,
Laura Cailly
Affiliations:
CHU Poitiers,Poitiers,France
,
Emilie Cayssials
Affiliations:
CHU Poitiers,Poitiers,France
,
Pilar Gallego
Affiliations:
CHU Poitiers,Poitiers,France
,
Jose Torregrosa
Affiliations:
CHU Poitiers,Poitiers,France
,
Deborah Desmier
Affiliations:
CHU Poitiers,Poitiers,France
,
Thomas Systchenko
Affiliations:
CHU Poitiers,Poitiers,France
,
Géraldine Durand
Affiliations:
CHU Poitiers,Poitiers,France
,
Sabrina Bouyer
Affiliations:
CHU Poitiers,Poitiers,France
,
Franck Bridoux
Affiliations:
CHU Poitiers,Poitiers,France
,
Audrey Sibille
Affiliations:
CHU Poitiers,Poitiers,France
,
Florent Joly
Affiliations:
CHU Poitiers,Poitiers,France
,
Gaelle Olivier
Affiliations:
CH Niort,Niort,France
,
Carine Motard
Affiliations:
CH Niort,Niort,France
,
Christophe Roul
Affiliations:
CH La Rochelle,La Rochelle,France
,
Anne Corby
Affiliations:
CH La Rochelle,La Rochelle,France
,
Cécile Tomowiak
Affiliations:
CHU Poitiers,Poitiers,France
,
Stephanie Guidez
Affiliations:
CHU Poitiers,Poitiers,France
Xavier Leleu
Affiliations:
CHU Poitiers,Poitiers,France
EHA Library. Gruchet C. 06/12/20; 293542; EP1053
Dr. Cécile Gruchet
Dr. Cécile Gruchet
Contributions
Abstract

Abstract: EP1053

Type: e-Poster

Presentation during EHA25: All e-Poster 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.

Background
Carfilzomib, Revlimid and Dexamethasone (KRd) combination has emerged in recent years as a promising treatment for multiple myeloma (MM), particularly in relapsed and refractory multiple myeloma (RRMM). Previous studies already prooved that the use of weekly Carfilzomib at dose of 56mg/m2 have an acceptable safety profile with similar efficacy to the twice-weekly regimen (dose of 27mg/m2). Nevertheless, despite encouraging overall response rates in multi-treated patients, we know that after discontinuation of treatment, the majority of patients will relapse more or less early.

Aims
In this study, we report new data regarding the prolonged use of the KRd combination administered until progression.

Methods
42 patients with RRMM (median age : 59 years, range 33 – 76) treated in Poitiers hospital was includied. 36 patients have 1 prior line of treatment and 6 patients have 2 prior line. All the patients received treatment by KRd until progression or significant adverse event. Carfilzomib was administered at 56mg/m2 on days 1,8,15 ;  Lenalidomide was given 21/28 days at 25mg and Dexamethasone was administered weekly.

Results
The median number of KRd cycles is 15 (range from 1 to 44) with 8/42 patients (19%) who received more than 30 cycles. Overall response rate (ORR) was 80,9% with a median DOR of 14 months (range 2 to 41).18/42 patients (42,8%) achieving complete response (CR) and 6 patients have negative MRD at 10-6 and normalized PET CT. Median time to best response is 9 months (range from 1 to 24). With a median follow-up at start of KRd of 25 months, 20/42 patients (47,6%) died and 21/42 patients (50%) relapsed. Median of OS is not reached and the median PFS and EFS was at 16 months (range 1 to 44).  22 patients (53,3%) have pejorative prognostic factor including cytogenetic characteristic (t(4;14) or deletion 17p), presence of extramedullary disease and presence of plasmablastic cells. In this subgroup, ORR was 77,3% including 8 patients with CR and he median of PFS and OS war respectively 17 month (range 1 to 43) and 26,4 months (range 2,5 to 43,1). Only 4 patients stopped KRd for safety issues. Hematologic and non-hematologic adverse events ≥ grade 3 were reported in 57% and 36% of patients. Adverse events ≥ grade 3 seen in ≥10% of patients were neutropenia, thrombocytopenia, vomiting and pyrexia. Of note, 11 patients (26,2%) were ≥ 65 years old and these patients showed similar data compared to the studied cohort.

Conclusion
Prolonged exposure to weekly KRd shows promising results in terms of overall survival and progression-free survival even in poorly prognostic disease.  Interestingly, prolonged KRd treatment can improve the depth of response in some patients. Moreover, treatment until progression have acceptable tolerance profile even on frailty patients. Further studies are warranted to confirm this data on a larger population for validate the concept of long duration treatment using Carfilzomib weekly.

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

Keyword(s): Immunomodulatory thalidomide analog, Myeloma, Progression, Proteasome inhibitor

Abstract: EP1053

Type: e-Poster

Presentation during EHA25: All e-Poster 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.

Background
Carfilzomib, Revlimid and Dexamethasone (KRd) combination has emerged in recent years as a promising treatment for multiple myeloma (MM), particularly in relapsed and refractory multiple myeloma (RRMM). Previous studies already prooved that the use of weekly Carfilzomib at dose of 56mg/m2 have an acceptable safety profile with similar efficacy to the twice-weekly regimen (dose of 27mg/m2). Nevertheless, despite encouraging overall response rates in multi-treated patients, we know that after discontinuation of treatment, the majority of patients will relapse more or less early.

Aims
In this study, we report new data regarding the prolonged use of the KRd combination administered until progression.

Methods
42 patients with RRMM (median age : 59 years, range 33 – 76) treated in Poitiers hospital was includied. 36 patients have 1 prior line of treatment and 6 patients have 2 prior line. All the patients received treatment by KRd until progression or significant adverse event. Carfilzomib was administered at 56mg/m2 on days 1,8,15 ;  Lenalidomide was given 21/28 days at 25mg and Dexamethasone was administered weekly.

Results
The median number of KRd cycles is 15 (range from 1 to 44) with 8/42 patients (19%) who received more than 30 cycles. Overall response rate (ORR) was 80,9% with a median DOR of 14 months (range 2 to 41).18/42 patients (42,8%) achieving complete response (CR) and 6 patients have negative MRD at 10-6 and normalized PET CT. Median time to best response is 9 months (range from 1 to 24). With a median follow-up at start of KRd of 25 months, 20/42 patients (47,6%) died and 21/42 patients (50%) relapsed. Median of OS is not reached and the median PFS and EFS was at 16 months (range 1 to 44).  22 patients (53,3%) have pejorative prognostic factor including cytogenetic characteristic (t(4;14) or deletion 17p), presence of extramedullary disease and presence of plasmablastic cells. In this subgroup, ORR was 77,3% including 8 patients with CR and he median of PFS and OS war respectively 17 month (range 1 to 43) and 26,4 months (range 2,5 to 43,1). Only 4 patients stopped KRd for safety issues. Hematologic and non-hematologic adverse events ≥ grade 3 were reported in 57% and 36% of patients. Adverse events ≥ grade 3 seen in ≥10% of patients were neutropenia, thrombocytopenia, vomiting and pyrexia. Of note, 11 patients (26,2%) were ≥ 65 years old and these patients showed similar data compared to the studied cohort.

Conclusion
Prolonged exposure to weekly KRd shows promising results in terms of overall survival and progression-free survival even in poorly prognostic disease.  Interestingly, prolonged KRd treatment can improve the depth of response in some patients. Moreover, treatment until progression have acceptable tolerance profile even on frailty patients. Further studies are warranted to confirm this data on a larger population for validate the concept of long duration treatment using Carfilzomib weekly.

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

Keyword(s): Immunomodulatory thalidomide analog, Myeloma, Progression, Proteasome inhibitor

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