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IXAZOMIB, POMALIDOMIDE AND DEXAMETHASONE (IXPD) IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM) CHARACTERIZED WITH HIGH-RISK CYTOGENETICS. IFM 2014-01
Author(s): ,
Arthur Bobin
Affiliations:
CHU de Poitiers,Poitiers,France;CHU de Poitiers,Poitiers,Frankreich;CHU de Poitiers,Poitiers,Francia;CHU de Poitiers,Poitiers,France;CHU de Poitiers,Poitiers,Francia;CHU de Poitiers,Poitiers,Frankrijk;CHU de Poitiers,Poitiers,França;CHU de Poitiers,Poitiers,Франция ;CHU de Poitiers,Poitiers,Frankrike
,
Salomon Manier
Affiliations:
chu de lille,lille,France;chu de lille,lille,Frankreich;chu de lille,lille,Francia;chu de lille,lille,France;chu de lille,lille,Francia;chu de lille,lille,Frankrijk;chu de lille,lille,França;chu de lille,lille,Франция ;chu de lille,lille,Frankrike
,
Joe De Keizer
Affiliations:
CHU de Poitiers,Poitiers,France;CHU de Poitiers,Poitiers,Frankreich;CHU de Poitiers,Poitiers,Francia;CHU de Poitiers,Poitiers,France;CHU de Poitiers,Poitiers,Francia;CHU de Poitiers,Poitiers,Frankrijk;CHU de Poitiers,Poitiers,França;CHU de Poitiers,Poitiers,Франция ;CHU de Poitiers,Poitiers,Frankrike
,
Lionel Karlin
Affiliations:
CHU de Lyon,Lyon,France;CHU de Lyon,Lyon,Frankreich;CHU de Lyon,Lyon,Francia;CHU de Lyon,Lyon,France;CHU de Lyon,Lyon,Francia;CHU de Lyon,Lyon,Frankrijk;CHU de Lyon,Lyon,França;CHU de Lyon,Lyon,Франция ;CHU de Lyon,Lyon,Frankrike
,
Aurore Perrot
Affiliations:
CHU de Toulouse,Toulouse,France;CHU de Toulouse,Toulouse,Frankreich;CHU de Toulouse,Toulouse,Francia;CHU de Toulouse,Toulouse,France;CHU de Toulouse,Toulouse,Francia;CHU de Toulouse,Toulouse,Frankrijk;CHU de Toulouse,Toulouse,França;CHU de Toulouse,Toulouse,Франция ;CHU de Toulouse,Toulouse,Frankrike
,
Cyrille Hulin
Affiliations:
CHU de Bordeaux,Bordeaux,France;CHU de Bordeaux,Bordeaux,Frankreich;CHU de Bordeaux,Bordeaux,Francia;CHU de Bordeaux,Bordeaux,France;CHU de Bordeaux,Bordeaux,Francia;CHU de Bordeaux,Bordeaux,Frankrijk;CHU de Bordeaux,Bordeaux,França;CHU de Bordeaux,Bordeaux,Франция ;CHU de Bordeaux,Bordeaux,Frankrike
,
Denis Caillot
Affiliations:
CHU de Dijon,Dijon,France;CHU de Dijon,Dijon,Frankreich;CHU de Dijon,Dijon,Francia;CHU de Dijon,Dijon,France;CHU de Dijon,Dijon,Francia;CHU de Dijon,Dijon,Frankrijk;CHU de Dijon,Dijon,França;CHU de Dijon,Dijon,Франция ;CHU de Dijon,Dijon,Frankrike
,
Clara Mariette
Affiliations:
CHU de Grenoble,Grenoble,France;CHU de Grenoble,Grenoble,Frankreich;CHU de Grenoble,Grenoble,Francia;CHU de Grenoble,Grenoble,France;CHU de Grenoble,Grenoble,Francia;CHU de Grenoble,Grenoble,Frankrijk;CHU de Grenoble,Grenoble,França;CHU de Grenoble,Grenoble,Франция ;CHU de Grenoble,Grenoble,Frankrike
,
Pascal Lenain
Affiliations:
CHU de Rouen,Rouen,France;CHU de Rouen,Rouen,Frankreich;CHU de Rouen,Rouen,Francia;CHU de Rouen,Rouen,France;CHU de Rouen,Rouen,Francia;CHU de Rouen,Rouen,Frankrijk;CHU de Rouen,Rouen,França;CHU de Rouen,Rouen,Франция ;CHU de Rouen,Rouen,Frankrike
,
Valentine Richez
Affiliations:
CHU de Nice,Nice,France;CHU de Nice,Nice,Frankreich;CHU de Nice,Nice,Francia;CHU de Nice,Nice,France;CHU de Nice,Nice,Francia;CHU de Nice,Nice,Frankrijk;CHU de Nice,Nice,França;CHU de Nice,Nice,Франция ;CHU de Nice,Nice,Frankrike
,
Mourad Tiab
Affiliations:
CH la Roche sur Yon,La Roche Sur Yon,France;CH la Roche sur Yon,La Roche Sur Yon,Frankreich;CH la Roche sur Yon,La Roche Sur Yon,Francia;CH la Roche sur Yon,La Roche Sur Yon,France;CH la Roche sur Yon,La Roche Sur Yon,Francia;CH la Roche sur Yon,La Roche Sur Yon,Frankrijk;CH la Roche sur Yon,La Roche Sur Yon,França;CH la Roche sur Yon,La Roche Sur Yon,Франция ;CH la Roche sur Yon,La Roche Sur Yon,
,
Cyrille Touzeau
Affiliations:
CHU de Nantes,Nantes,France;CHU de Nantes,Nantes,Frankreich;CHU de Nantes,Nantes,Francia;CHU de Nantes,Nantes,France;CHU de Nantes,Nantes,Francia;CHU de Nantes,Nantes,Frankrijk;CHU de Nantes,Nantes,França;CHU de Nantes,Nantes,Франция ;CHU de Nantes,Nantes,Frankrike
,
Arnaud Jaccard
Affiliations:
CHU de Limoges,Limoges,France;CHU de Limoges,Limoges,Frankreich;CHU de Limoges,Limoges,Francia;CHU de Limoges,Limoges,France;CHU de Limoges,Limoges,Francia;CHU de Limoges,Limoges,Frankrijk;CHU de Limoges,Limoges,França;CHU de Limoges,Limoges,Франция ;CHU de Limoges,Limoges,Frankrike
,
Olivier Decaux
Affiliations:
CHU de Rennes,Rennes,France;CHU de Rennes,Rennes,Frankreich;CHU de Rennes,Rennes,Francia;CHU de Rennes,Rennes,France;CHU de Rennes,Rennes,Francia;CHU de Rennes,Rennes,Frankrijk;CHU de Rennes,Rennes,França;CHU de Rennes,Rennes,Франция ;CHU de Rennes,Rennes,Frankrike
,
Carla Araujo
Affiliations:
CH de Bayonne,Bayonne,France;CH de Bayonne,Bayonne,Frankreich;CH de Bayonne,Bayonne,Francia;CH de Bayonne,Bayonne,France;CH de Bayonne,Bayonne,Francia;CH de Bayonne,Bayonne,Frankrijk;CH de Bayonne,Bayonne,França;CH de Bayonne,Bayonne,Франция ;CH de Bayonne,Bayonne,Frankrike
,
Karim Belhadj
Affiliations:
CHU de Créteil-APHP,Créteil,France;CHU de Créteil-APHP,Créteil,Frankreich;CHU de Créteil-APHP,Créteil,Francia;CHU de Créteil-APHP,Créteil,France;CHU de Créteil-APHP,Créteil,Francia;CHU de Créteil-APHP,Créteil,Frankrijk;CHU de Créteil-APHP,Créteil,França;CHU de Créteil-APHP,Créteil,Франция ;CHU de Créteil-APHP,Créteil,Frankrike
,
Lofti Benboubker
Affiliations:
CHU de Tours,Tours,France;CHU de Tours,Tours,Frankreich;CHU de Tours,Tours,Francia;CHU de Tours,Tours,France;CHU de Tours,Tours,Francia;CHU de Tours,Tours,Frankrijk;CHU de Tours,Tours,França;CHU de Tours,Tours,Франция ;CHU de Tours,Tours,Frankrike
,
Cécile Déal
Affiliations:
Intergroupe Francophone du Myélome,Paris,France;Intergroupe Francophone du Myélome,Paris,Frankreich;Intergroupe Francophone du Myélome,Paris,Francia;Intergroupe Francophone du Myélome,Paris,France;Intergroupe Francophone du Myélome,Paris,Francia;Intergroupe Francophone du Myélome,Paris,Frankrijk;Intergroupe Francophone du Myélome,Paris,França;Intergroupe Francophone du Myélome,Paris,Франция ;Inter
,
Margaret Macro
Affiliations:
CHU de Caen,Caen,France;CHU de Caen,Caen,Frankreich;CHU de Caen,Caen,Francia;CHU de Caen,Caen,France;CHU de Caen,Caen,Francia;CHU de Caen,Caen,Frankrijk;CHU de Caen,Caen,França;CHU de Caen,Caen,Франция ;CHU de Caen,Caen,Frankrike
,
Laure Vincent
Affiliations:
CHU de Montpellier,Montpellier,France;CHU de Montpellier,Montpellier,Frankreich;CHU de Montpellier,Montpellier,Francia;CHU de Montpellier,Montpellier,France;CHU de Montpellier,Montpellier,Francia;CHU de Montpellier,Montpellier,Frankrijk;CHU de Montpellier,Montpellier,França;CHU de Montpellier,Montpellier,Франция ;CHU de Montpellier,Montpellier,Frankrike
,
bertrand Arnulf
Affiliations:
Hopital Saint Louis,Paris,France;Hopital Saint Louis,Paris,Frankreich;Hopital Saint Louis,Paris,Francia;Hopital Saint Louis,Paris,France;Hopital Saint Louis,Paris,Francia;Hopital Saint Louis,Paris,Frankrijk;Hopital Saint Louis,Paris,França;Hopital Saint Louis,Paris,Франция ;Hopital Saint Louis,Paris,Frankrike
,
Benoit Bareau
Affiliations:
Hopital Privé Sevigne,Cesson Sevigne,France;Hopital Privé Sevigne,Cesson Sevigne,Frankreich;Hopital Privé Sevigne,Cesson Sevigne,Francia;Hopital Privé Sevigne,Cesson Sevigne,France;Hopital Privé Sevigne,Cesson Sevigne,Francia;Hopital Privé Sevigne,Cesson Sevigne,Frankrijk;Hopital Privé Sevigne,Cesson Sevigne,França;Hopital Privé Sevigne,Cesson Sevigne,Франция ;Hopital Privé Sevigne,Cesson Sevigne,
,
Thorsten Braun
Affiliations:
Hopital Avicenne,Bobigny,France;Hopital Avicenne,Bobigny,Frankreich;Hopital Avicenne,Bobigny,Francia;Hopital Avicenne,Bobigny,France;Hopital Avicenne,Bobigny,Francia;Hopital Avicenne,Bobigny,Frankrijk;Hopital Avicenne,Bobigny,França;Hopital Avicenne,Bobigny,Франция ;Hopital Avicenne,Bobigny,Frankrike
,
Claire Calmettes
Affiliations:
CH de Périgueux,Périgueux,France;CH de Périgueux,Périgueux,Frankreich;CH de Périgueux,Périgueux,Francia;CH de Périgueux,Périgueux,France;CH de Périgueux,Périgueux,Francia;CH de Périgueux,Périgueux,Frankrijk;CH de Périgueux,Périgueux,França;CH de Périgueux,Périgueux,Франция ;CH de Périgueux,Périgueux,Frankrike
,
Dib mamoun
Affiliations:
CHU de Angers,Angers,France;CHU de Angers,Angers,Frankreich;CHU de Angers,Angers,Francia;CHU de Angers,Angers,France;CHU de Angers,Angers,Francia;CHU de Angers,Angers,Frankrijk;CHU de Angers,Angers,França;CHU de Angers,Angers,Франция ;CHU de Angers,Angers,Frankrike
,
Hacene Zerazhi
Affiliations:
CH de Avignon,Avignon,France;CH de Avignon,Avignon,Frankreich;CH de Avignon,Avignon,Francia;CH de Avignon,Avignon,France;CH de Avignon,Avignon,Francia;CH de Avignon,Avignon,Frankrijk;CH de Avignon,Avignon,França;CH de Avignon,Avignon,Франция ;CH de Avignon,Avignon,Frankrike
,
Helene Demarquette
Affiliations:
CH de Dunkerque,Dunkerque,France;CH de Dunkerque,Dunkerque,Frankreich;CH de Dunkerque,Dunkerque,Francia;CH de Dunkerque,Dunkerque,France;CH de Dunkerque,Dunkerque,Francia;CH de Dunkerque,Dunkerque,Frankrijk;CH de Dunkerque,Dunkerque,França;CH de Dunkerque,Dunkerque,Франция ;CH de Dunkerque,Dunkerque,Frankrike
,
Pierre Feugier
Affiliations:
CHRU de Nancy,Nancy,France;CHRU de Nancy,Nancy,Frankreich;CHRU de Nancy,Nancy,Francia;CHRU de Nancy,Nancy,France;CHRU de Nancy,Nancy,Francia;CHRU de Nancy,Nancy,Frankrijk;CHRU de Nancy,Nancy,França;CHRU de Nancy,Nancy,Франция ;CHRU de Nancy,Nancy,Frankrike
,
Cécile Fohrer-sonntag
Affiliations:
CHU de Strasbourg,Strasbourg,France;CHU de Strasbourg,Strasbourg,Frankreich;CHU de Strasbourg,Strasbourg,Francia;CHU de Strasbourg,Strasbourg,France;CHU de Strasbourg,Strasbourg,Francia;CHU de Strasbourg,Strasbourg,Frankrijk;CHU de Strasbourg,Strasbourg,França;CHU de Strasbourg,Strasbourg,Франция ;CHU de Strasbourg,Strasbourg,Frankrike
,
Sophie Godet
Affiliations:
CHU de Reims,Reims,France;CHU de Reims,Reims,Frankreich;CHU de Reims,Reims,Francia;CHU de Reims,Reims,France;CHU de Reims,Reims,Francia;CHU de Reims,Reims,Frankrijk;CHU de Reims,Reims,França;CHU de Reims,Reims,Франция ;CHU de Reims,Reims,Frankrike
,
Marie-Odile Petillon
Affiliations:
chu de lille,lille,France;chu de lille,lille,Frankreich;chu de lille,lille,Francia;chu de lille,lille,France;chu de lille,lille,Francia;chu de lille,lille,Frankrijk;chu de lille,lille,França;chu de lille,lille,Франция ;chu de lille,lille,Frankrike
,
Hervé Avet-Loiseau
Affiliations:
CHU de Toulouse,Toulouse,France;CHU de Toulouse,Toulouse,Frankreich;CHU de Toulouse,Toulouse,Francia;CHU de Toulouse,Toulouse,France;CHU de Toulouse,Toulouse,Francia;CHU de Toulouse,Toulouse,Frankrijk;CHU de Toulouse,Toulouse,França;CHU de Toulouse,Toulouse,Франция ;CHU de Toulouse,Toulouse,Frankrike
Xavier Leleu
Affiliations:
CHU de Poitiers,Poitiers,France;CHU de Poitiers,Poitiers,Frankreich;CHU de Poitiers,Poitiers,Francia;CHU de Poitiers,Poitiers,France;CHU de Poitiers,Poitiers,Francia;CHU de Poitiers,Poitiers,Frankrijk;CHU de Poitiers,Poitiers,França;CHU de Poitiers,Poitiers,Франция ;CHU de Poitiers,Poitiers,Frankrike
(Abstract release date: 05/12/22) EHA Library. Leleu X. 06/10/22; 357752; P891
Dr. Xavier Leleu
Dr. Xavier Leleu
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: P891

Type: Poster presentation

Session title: Myeloma and other monoclonal gammopathies - Clinical

Background
High risk (HR) cytogenetics remains of poor prognosis, particularly in the RRMM setting. IFM 2010-02, Pd in advanced HR RRMM, had demonstrated limited activity with no addition of a proteasome inhibitor (PI), and a good safety profile. We hypothesized that addition of Ixazomib (oral PI at increased dose density) to Pd (IxPd) in HR RRMM would improve convenience, thus adherence to treatment, and in parallel improve efficacy with no increased toxicity.

Aims

We aimed to determine the efficacy and safety profile of the association ixazomib, pomalidomide and dexamethasone HR RRMM.

 

Methods

Eligible patients had a RRMM in L2 refractory to lenalidomide but not to pomalidomide and ixazomib. HR was defined by presence of either del(17p) and/or t(4;14) at diagnosis or study entry. Patients received 17 induction cycles, 21-days long, consisting of ixazomib 3mg/day (d 1, 4, 8 and 11), pomalidomide 4mg/day (d1 to 14) and weekly dexamethasone, followed by a maintenance phase of 28-day cycles with ixazomib 4mg/day (d 1, 8 and 15) and pomalidomide 4mg/day (d 1 to 21), until progression. The primary endpoint was time to progression (TTP). The number of patients to be recruited was initially calculated based on an expected doubling of the median TTP obtained in IFM 2010-02 with Pd in either 2 HR RRMM population, but the number was recalculated due to difficulties in recruitment to demonstrate an expected doubling of the median TTP from 3 months, as a whole. No statistical comparison can be done across HR groups given that the study was powered to analyze the 2 groups as a whole and not separately with 26 patients.

Results

Twenty-six patients were enrolled in the study. Median age was 72 years (Interquartile range: 67-78). Ten patients presented with del(17p) and twelve patients with t(4;14). All patients were refractory to lenalidomide.

With a median follow-up time of 9.8 months, the median TTP was 9.7 months (95% confidence interval (CI) 4.4;-). The median OS was 12.2 months (CI95% 11.1;-). The ORR and VGPR rate was 15 (58%) pts and 7 pts (27%) in the study as a whole. The ≥VGPR rate was 30% and 33% in del(17p) and t(4;14), respectively. No CR was observed with IxPd in our series.

The most common adverse events (≥10% occurrence) were neutropenia (n=13), thrombocytopenia (n=12), asthenia (n=9), anemia (n=7), rash (n=4), diarrhea (n=3), dizziness (n=3), general physical health deterioration (n=3), muscle spasms (n=3), peripheral oedema (n=3), pyrexia (n=3). Ten SUSARs were declared with no modification to the safety profile of ixazomib and pomalidomide according to the independent data monitoring committee.

Conclusion

The study IFM 2014-01/IxPd in HR L2 RRMM met its primary end point objective since the median TTP was superior to 3 months, the median TTP reported in IFM2010-02 as a whole, with the addition of Ixazomib to Pomalidomide and dexamethasone in this population characterized with a very poor outcome. This data confirms the importance of proteasome inhibitors in HR RRMM. This phase 2 study needs confirmation in a larger cohort.

Keyword(s): Cytogenetics, High risk, 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: P891

Type: Poster presentation

Session title: Myeloma and other monoclonal gammopathies - Clinical

Background
High risk (HR) cytogenetics remains of poor prognosis, particularly in the RRMM setting. IFM 2010-02, Pd in advanced HR RRMM, had demonstrated limited activity with no addition of a proteasome inhibitor (PI), and a good safety profile. We hypothesized that addition of Ixazomib (oral PI at increased dose density) to Pd (IxPd) in HR RRMM would improve convenience, thus adherence to treatment, and in parallel improve efficacy with no increased toxicity.

Aims

We aimed to determine the efficacy and safety profile of the association ixazomib, pomalidomide and dexamethasone HR RRMM.

 

Methods

Eligible patients had a RRMM in L2 refractory to lenalidomide but not to pomalidomide and ixazomib. HR was defined by presence of either del(17p) and/or t(4;14) at diagnosis or study entry. Patients received 17 induction cycles, 21-days long, consisting of ixazomib 3mg/day (d 1, 4, 8 and 11), pomalidomide 4mg/day (d1 to 14) and weekly dexamethasone, followed by a maintenance phase of 28-day cycles with ixazomib 4mg/day (d 1, 8 and 15) and pomalidomide 4mg/day (d 1 to 21), until progression. The primary endpoint was time to progression (TTP). The number of patients to be recruited was initially calculated based on an expected doubling of the median TTP obtained in IFM 2010-02 with Pd in either 2 HR RRMM population, but the number was recalculated due to difficulties in recruitment to demonstrate an expected doubling of the median TTP from 3 months, as a whole. No statistical comparison can be done across HR groups given that the study was powered to analyze the 2 groups as a whole and not separately with 26 patients.

Results

Twenty-six patients were enrolled in the study. Median age was 72 years (Interquartile range: 67-78). Ten patients presented with del(17p) and twelve patients with t(4;14). All patients were refractory to lenalidomide.

With a median follow-up time of 9.8 months, the median TTP was 9.7 months (95% confidence interval (CI) 4.4;-). The median OS was 12.2 months (CI95% 11.1;-). The ORR and VGPR rate was 15 (58%) pts and 7 pts (27%) in the study as a whole. The ≥VGPR rate was 30% and 33% in del(17p) and t(4;14), respectively. No CR was observed with IxPd in our series.

The most common adverse events (≥10% occurrence) were neutropenia (n=13), thrombocytopenia (n=12), asthenia (n=9), anemia (n=7), rash (n=4), diarrhea (n=3), dizziness (n=3), general physical health deterioration (n=3), muscle spasms (n=3), peripheral oedema (n=3), pyrexia (n=3). Ten SUSARs were declared with no modification to the safety profile of ixazomib and pomalidomide according to the independent data monitoring committee.

Conclusion

The study IFM 2014-01/IxPd in HR L2 RRMM met its primary end point objective since the median TTP was superior to 3 months, the median TTP reported in IFM2010-02 as a whole, with the addition of Ixazomib to Pomalidomide and dexamethasone in this population characterized with a very poor outcome. This data confirms the importance of proteasome inhibitors in HR RRMM. This phase 2 study needs confirmation in a larger cohort.

Keyword(s): Cytogenetics, High risk, Myeloma, Relapse

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