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IXAZOMIB AND DARATUMUMAB WITHOUT DEXAMETHASONE (I-DARA) IN ELDERLY FRAIL RELAPSING MYELOMA (RRMM) PATIENTS: RESULTS OF THE PHASE 2 STUDY IFM 2018-02 OF THE INTERGROUPE FRANCOPHONE DU MYELOME (IFM).
Author(s): ,
Margaret Macro
Affiliations:
HEMATOLOGY IHBN,University Hospital,CAEN,France;HEMATOLOGY IHBN,University Hospital,CAEN,Frankreich;HEMATOLOGY IHBN,University Hospital,CAEN,Francia;HEMATOLOGY IHBN,University Hospital,CAEN,France;HEMATOLOGY IHBN,University Hospital,CAEN,Francia;HEMATOLOGY IHBN,University Hospital,CAEN,Frankrijk;HEMATOLOGY IHBN,University Hospital,CAEN,França;HEMATOLOGY IHBN,University Hospital,CAEN,Франция ;HEMAT
,
Cyrille Touzeau
Affiliations:
HEMATOLOGY ,University Hospital,Nantes,France;HEMATOLOGY ,University Hospital,Nantes,Frankreich;HEMATOLOGY ,University Hospital,Nantes,Francia;HEMATOLOGY ,University Hospital,Nantes,France;HEMATOLOGY ,University Hospital,Nantes,Francia;HEMATOLOGY ,University Hospital,Nantes,Frankrijk;HEMATOLOGY ,University Hospital,Nantes,França;HEMATOLOGY ,University Hospital,Nantes,Франция ;HEMATOLOGY ,Universit
,
Clara Mariette
Affiliations:
HEMATOLOGY,University Hospital,Grenoble,France;HEMATOLOGY,University Hospital,Grenoble,Frankreich;HEMATOLOGY,University Hospital,Grenoble,Francia;HEMATOLOGY,University Hospital,Grenoble,France;HEMATOLOGY,University Hospital,Grenoble,Francia;HEMATOLOGY,University Hospital,Grenoble,Frankrijk;HEMATOLOGY,University Hospital,Grenoble,França;HEMATOLOGY,University Hospital,Grenoble,Франция ;HEMATOLOGY,Un
,
Salomon Manier
Affiliations:
Hematology,University Hospital,Lille,France;Hematology,University Hospital,Lille,Frankreich;Hematology,University Hospital,Lille,Francia;Hematology,University Hospital,Lille,France;Hematology,University Hospital,Lille,Francia;Hematology,University Hospital,Lille,Frankrijk;Hematology,University Hospital,Lille,França;Hematology,University Hospital,Lille,Франция ;Hematology,University Hospital,Lille,
,
Sabine Brechignac
Affiliations:
Hematology,University Hospital,Paris,France;Hematology,University Hospital,Paris,Frankreich;Hematology,University Hospital,Paris,Francia;Hematology,University Hospital,Paris,France;Hematology,University Hospital,Paris,Francia;Hematology,University Hospital,Paris,Frankrijk;Hematology,University Hospital,Paris,França;Hematology,University Hospital,Paris,Франция ;Hematology,University Hospital,Paris,
,
Laure Vincent
Affiliations:
Hematology,University Hospital,Montpellier,France;Hematology,University Hospital,Montpellier,Frankreich;Hematology,University Hospital,Montpellier,Francia;Hematology,University Hospital,Montpellier,France;Hematology,University Hospital,Montpellier,Francia;Hematology,University Hospital,Montpellier,Frankrijk;Hematology,University Hospital,Montpellier,França;Hematology,University Hospital,Montpellie
,
Bejamin Hebraud
Affiliations:
Hematology,University Hospital,Toulouse,France;Hematology,University Hospital,Toulouse,Frankreich;Hematology,University Hospital,Toulouse,Francia;Hematology,University Hospital,Toulouse,France;Hematology,University Hospital,Toulouse,Francia;Hematology,University Hospital,Toulouse,Frankrijk;Hematology,University Hospital,Toulouse,França;Hematology,University Hospital,Toulouse,Франция ;Hematology,Un
,
Olivier Decaux
Affiliations:
Hematology,University Hospital,Rennes,France;Hematology,University Hospital,Rennes,Frankreich;Hematology,University Hospital,Rennes,Francia;Hematology,University Hospital,Rennes,France;Hematology,University Hospital,Rennes,Francia;Hematology,University Hospital,Rennes,Frankrijk;Hematology,University Hospital,Rennes,França;Hematology,University Hospital,Rennes,Франция ;Hematology,University Hospita
,
Samantha Schulmann
Affiliations:
Hematology,University Hospital,Nancy,France;Hematology,University Hospital,Nancy,Frankreich;Hematology,University Hospital,Nancy,Francia;Hematology,University Hospital,Nancy,France;Hematology,University Hospital,Nancy,Francia;Hematology,University Hospital,Nancy,Frankrijk;Hematology,University Hospital,Nancy,França;Hematology,University Hospital,Nancy,Франция ;Hematology,University Hospital,Nancy,
,
Caroline Lenoir
Affiliations:
Hematology,Private Hospital,Bordeaux,France;Hematology,Private Hospital,Bordeaux,Frankreich;Hematology,Private Hospital,Bordeaux,Francia;Hematology,Private Hospital,Bordeaux,France;Hematology,Private Hospital,Bordeaux,Francia;Hematology,Private Hospital,Bordeaux,Frankrijk;Hematology,Private Hospital,Bordeaux,França;Hematology,Private Hospital,Bordeaux,Франция ;Hematology,Private Hospital,Bordeaux,
,
Pascal Godmer
Affiliations:
Hematology,Community Hospital,Vannes,France;Hematology,Community Hospital,Vannes,Frankreich;Hematology,Community Hospital,Vannes,Francia;Hematology,Community Hospital,Vannes,France;Hematology,Community Hospital,Vannes,Francia;Hematology,Community Hospital,Vannes,Frankrijk;Hematology,Community Hospital,Vannes,França;Hematology,Community Hospital,Vannes,Франция ;Hematology,Community Hospital,Vannes,
,
Agathe Farge
Affiliations:
Hematology,University Hospital,CAEN,France;Hematology,University Hospital,CAEN,Frankreich;Hematology,University Hospital,CAEN,Francia;Hematology,University Hospital,CAEN,France;Hematology,University Hospital,CAEN,Francia;Hematology,University Hospital,CAEN,Frankrijk;Hematology,University Hospital,CAEN,França;Hematology,University Hospital,CAEN,Франция ;Hematology,University Hospital,CAEN,Frankrike
,
Laure Peyro Saint Paul
Affiliations:
Clinical Research,University Hospital,CAEN,France;Clinical Research,University Hospital,CAEN,Frankreich;Clinical Research,University Hospital,CAEN,Francia;Clinical Research,University Hospital,CAEN,France;Clinical Research,University Hospital,CAEN,Francia;Clinical Research,University Hospital,CAEN,Frankrijk;Clinical Research,University Hospital,CAEN,França;Clinical Research,University Hospital,CAE
,
Jean-Jacques Parienti
Affiliations:
Clinical Research,University Hospital,CAEN,France;Clinical Research,University Hospital,CAEN,Frankreich;Clinical Research,University Hospital,CAEN,Francia;Clinical Research,University Hospital,CAEN,France;Clinical Research,University Hospital,CAEN,Francia;Clinical Research,University Hospital,CAEN,Frankrijk;Clinical Research,University Hospital,CAEN,França;Clinical Research,University Hospital,CAE
Xavier Leleu
Affiliations:
Hematology,University Hospital,Poitiers,France;Hematology,University Hospital,Poitiers,Frankreich;Hematology,University Hospital,Poitiers,Francia;Hematology,University Hospital,Poitiers,France;Hematology,University Hospital,Poitiers,Francia;Hematology,University Hospital,Poitiers,Frankrijk;Hematology,University Hospital,Poitiers,França;Hematology,University Hospital,Poitiers,Франция ;Hematology,Un
(Abstract release date: 05/12/22) EHA Library. Macro M. 06/10/22; 357789; P929
Margaret Macro
Margaret Macro
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P929

Type: Poster presentation

Session title: Myeloma and other monoclonal gammopathies - Clinical

Background
Frail patients with multiple myeloma have an inferior outcome, especially in the relapse setting. This adverse prognosis is mainly related to a high discontinuation rate due to treatment (Tx) related adverse events. 

Aims
The aim of this phase 2 study is to evaluate efficacy and tolerability of Ixazomib-Daratumumab (I-Dara) without Dexamethasone in elderly frail patients with relapsed myeloma (RRMM) (NCT03757221).

Methods
Ixa-Dara naïve RRMM patients received oral Ixazomib (4 mg: days 1, 8, 15), IV Daratumumab (16 mg/kg; days 1, 8, 15, 22, cycles 1-2; days 1, 15, cycles 3-6; days 1, cycles 7+) and IV Methylprednisolone before Daratumumab (100 mg at day 1, 8, cycle 1 and then 60 mg). They were enrolled after 1 or 2 prior therapy if their frailty score was ≥ 2 by IMWG score. The primary endpoint was ≥ very good partial response rate (VGPR) at one year. Secondary endpoints included overall response rate (ORR), progression free survival (PFS), overall survival (OS) & toxicity according to NCI-CTCAE version 5

Results
Sixty-three patients were screened and 55 enrolled between 03/2018 and 09/2021. Patient were at first (n = 36) or second relapse (n = 19). Thirty-three patients (60%) were previously exposed to bortezomib, 37 (67%) were previously exposed to lenalidomide (Len) and 20 (36 %) were refractory to Len. Median age was 82 (72-93). All patients had a frailty score ≥2 and 13 (24 %) had a 3 or 4 frailty score. In 41 patients ISS at diagnosis was stage I (n = 11), II (n = 18) or III (n = 12). Seventeen (36%) patients harbored high-risk (HR) cytogenetic, including t(4;14) (n = 8) or del17p (n = 10). The median duration of Tx among 28 pts with ongoing Tx was 10 months [5-32] at data cutoff (February, 2). The median duration of Tx among 27 pts who stopped Tx was 6 months [0-18]: 18 had progressive disease. Nine patients died during the study: Daratumumab-related bronchospasm (D1C1); Ixazomib-related overdose (C2); sepsis (n = 4), progressive disease (n = 3). Regarding toxicity, 27 pts had a ≥grade 3 AE (49%). The most common grade 3-4 toxicities were thrombocytopenia (n = 9), other cytopenias (n = 4), infection (n = 8), hypertension (n = 3) and gastrointestinal disorders (n = 3). Fourteen out of 28 were SAE including 5 infections, 1 bronchospasm, 1 acute respiratory failure and 2 ixazomib overdoses. Overall response rate, including minimal response, was 86 % with a ≥VGPR rate of 32 % in the whole group. In Len refractory patients the ORR was 82 % and ≥VGPR 41%, in HR cytogenetic patients ORR was 85 % and ≥VGPR 46%. With a median follow-up of 11.6 months median PFS is 16 months and median OS NR (76% estimated at one year).

Conclusion
In this elderly frail population Ixa-Dara is a feasible combination with favorable efficacy profile even in Len refractory and HR cytogenetic patients. Early toxicity remains a concern in this population eventhough more manageable with Dara SC.

Keyword(s): Elderly, Immunotherapy, Multiple myeloma, Relapse

Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P929

Type: Poster presentation

Session title: Myeloma and other monoclonal gammopathies - Clinical

Background
Frail patients with multiple myeloma have an inferior outcome, especially in the relapse setting. This adverse prognosis is mainly related to a high discontinuation rate due to treatment (Tx) related adverse events. 

Aims
The aim of this phase 2 study is to evaluate efficacy and tolerability of Ixazomib-Daratumumab (I-Dara) without Dexamethasone in elderly frail patients with relapsed myeloma (RRMM) (NCT03757221).

Methods
Ixa-Dara naïve RRMM patients received oral Ixazomib (4 mg: days 1, 8, 15), IV Daratumumab (16 mg/kg; days 1, 8, 15, 22, cycles 1-2; days 1, 15, cycles 3-6; days 1, cycles 7+) and IV Methylprednisolone before Daratumumab (100 mg at day 1, 8, cycle 1 and then 60 mg). They were enrolled after 1 or 2 prior therapy if their frailty score was ≥ 2 by IMWG score. The primary endpoint was ≥ very good partial response rate (VGPR) at one year. Secondary endpoints included overall response rate (ORR), progression free survival (PFS), overall survival (OS) & toxicity according to NCI-CTCAE version 5

Results
Sixty-three patients were screened and 55 enrolled between 03/2018 and 09/2021. Patient were at first (n = 36) or second relapse (n = 19). Thirty-three patients (60%) were previously exposed to bortezomib, 37 (67%) were previously exposed to lenalidomide (Len) and 20 (36 %) were refractory to Len. Median age was 82 (72-93). All patients had a frailty score ≥2 and 13 (24 %) had a 3 or 4 frailty score. In 41 patients ISS at diagnosis was stage I (n = 11), II (n = 18) or III (n = 12). Seventeen (36%) patients harbored high-risk (HR) cytogenetic, including t(4;14) (n = 8) or del17p (n = 10). The median duration of Tx among 28 pts with ongoing Tx was 10 months [5-32] at data cutoff (February, 2). The median duration of Tx among 27 pts who stopped Tx was 6 months [0-18]: 18 had progressive disease. Nine patients died during the study: Daratumumab-related bronchospasm (D1C1); Ixazomib-related overdose (C2); sepsis (n = 4), progressive disease (n = 3). Regarding toxicity, 27 pts had a ≥grade 3 AE (49%). The most common grade 3-4 toxicities were thrombocytopenia (n = 9), other cytopenias (n = 4), infection (n = 8), hypertension (n = 3) and gastrointestinal disorders (n = 3). Fourteen out of 28 were SAE including 5 infections, 1 bronchospasm, 1 acute respiratory failure and 2 ixazomib overdoses. Overall response rate, including minimal response, was 86 % with a ≥VGPR rate of 32 % in the whole group. In Len refractory patients the ORR was 82 % and ≥VGPR 41%, in HR cytogenetic patients ORR was 85 % and ≥VGPR 46%. With a median follow-up of 11.6 months median PFS is 16 months and median OS NR (76% estimated at one year).

Conclusion
In this elderly frail population Ixa-Dara is a feasible combination with favorable efficacy profile even in Len refractory and HR cytogenetic patients. Early toxicity remains a concern in this population eventhough more manageable with Dara SC.

Keyword(s): Elderly, Immunotherapy, Multiple myeloma, Relapse

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