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1939 Multicenter Open Label Phase 2 Study of Isatuximab Plus Pomalidomide and Dexamethasone with Carfilzomib in Relapsed or Refractory Multiple Myeloma. Iskpd - IFM2018-03

Program: Oral and Poster Abstracts
Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster I
Hematology Disease Topics & Pathways:
Combination therapy, Therapies
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Arthur Bobin1*, Jerome Lambert, MD, PhD2*, Stéphanie Ragot3*, Aurore Perrot, MD, PhD4*, Salomon Manier, MD, PhD5, Lionel Karlin6*, Denis Caillot, MD7*, Cyrille Hulin8*, Lotfi Benboubker, MD9*, Carla Araujo10*, Jean Fontan, MD11*, Thorsten Braun, MD, PhD12, Clara Mariette, MD13*, Elodie Scherman, MD14*, Olivier Decaux, MD, PhD15*, jean Sebastien Blade16*, Faida Keddar17*, Christophe Roul, MD18*, Mamoun Dib, MD19*, Jill Corre20*, Frederique Orsini21*, Laure Vincent, MD22*, Mohamad Mohty, MD PhD23, Cyrille Touzeau24,25*, Philippe Moreau, MD26*, Herve Avet Loiseau, MD, PhD27 and Xavier Leleu, MD, PhD28

1Service d'Hématologie et de thérapie cellulaire, CHU de Poitiers, Poitiers, France
2Biostatistics Department, University of Paris, AP-HP, Saint Louis Hospital, Paris, FRA
3Inserm CIC 1402, University Hospital, Poitiers, France
4Centre Hospitalier Universitaire de Toulouse, Service d'Hématologie, Toulouse, France
5Department of Medical Oncology, Hopital Claude Huriez, CHU Lille, Lille, France
6Service d’Hématologie Clinique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
7Hematology Department, Dijon University Hospital, Dijon, France
8Department of Hematology, University Hospital Bordeaux, Bordeaux, France
9Hématologie Thérapie Cellulaire, CHRU TOURS, Tours, FRA
10Centre Hospitalier de la Cote Basque, Bayonne, France, Bayonne, FRA
11Jean Minjoz Hôpital, Besancon, France
12Hematology, Avicenne Hospital, Bobigny, France
13Service d'Hématologie, CHU de Grenoble, Grenoble, France
14Hopital de Nimes, NIMES, FRA
15Service d'hématologie clinique, Centre Hospitalier Universitaire de Rennes, Rennes, France
16Hôpital d’Instruction des Armées Service de Médecine interne - Oncologie, Hôpital d’Instruction des Armées Sainte Anne, Toulon, France
17Centre Hospitalier Valenciennes, Valenciennes, France
18La Rochelle Hospital, La Rochelle, FRA
19Hématologie - CHU - Hôpital du Bocage, Angers, France
20Toulouse, and CRCT, Toulouse, France, Toulouse, France
21Service Hématologie, CH Annecy, ANNECY, France
22Department of Hematology, Montpellier University Hospital, Montpellier, France
23EBMT Paris study office / CEREST-TC, Paris, France, Department of Hematology, Saint Antoine Hospital, Paris, France, INSERM UMR 938, Sorbonne University, Paris, France
24Centre Hospitalier Universitaire (CHU) de Nantes, INSERM, Université de Nantes, Nantes, France
25University Hospital Hôtel Dieu, Nantes Cedex 1, FRA
26CHU de Nantes, Nantes, France
27Unite de Genomique du Myelome, IUC-Oncopole, Toulouse, France
28Department of Oncology, Hematology and Cellular Therapy, Poitiers University Hospital, Poitiers, France

Background. RRMM (relapsed or refractory multiple myeloma) remains a major change in the Myeloma disease development as it implies a shortening in overall survival with subsequent relapses; and consequently, RRMM is in constant need of novel treatment options to prolong survival. The triplet-based association of antiCD38 immunotherapy (antiCD38 IT) with either second generation of Imids (Pomalidomide) and dexamethasone or second-generation proteasome inhibitors (PI) such as Carfilzomib and dexamethasone has become the new standard of care in early relapse MM. However, quadruplet-based regimens (antiCD38 immunotherapy +Imids +PI +dexamethasone) have transformed the treatment landscape in the upfront setting, improving MRD (minimal residual disease) and survivals.


We hypothesized that a quadruplet-based regimens (antiCD38 immunotherapy +Imids +PI +dexamethasone) would further improved MRD and survival in early RRMM. Here, we describe a phase II multicentric, open-label study, of isatuximab (antiCD38 IT), pomalidomide and dexamethasone plus carfilzomib (IsKPd/ IFM2018-03, NCT04287855) for patients with early RRMM.


Study design and Methods. Approximately 90 patients will receive the association isatuximab, pomalidomide and dexamethasone with carfilzomib (IsKPd). Eligible patients are adults aged ≥18 years old with RRMM previously treated with 1 or 2 lines of therapy, including lenalidomide, prior to the study entry. Patients were excluded if they were refractory to any anti-CD38 monoclonal antibody or to carfilzomib, or if they were previously exposed to pomalidomide. Isatuximab will be given by IV route at 10 mg/kg on days 1, 8, 15, and 22 of cycle 1, on days 1 and 15 from cycle 2 to 12 and on day 1 only from cycle 13, 28-day cycles. Carfilzomib will be given by IV route at 20/27 mg/m² on days 1-2, 8-9, 15-16 during cycle 1, at 56mg/m² on days 1, 8, 15 from cycle 2 to 13 and at 56mg/m² on days 1 and 15 after cycle 13. Pomalidomide will be administered by oral route at 3 mg daily on days 1 to 21 in cycle 1 and at 4 mg daily from cycle 12. Dexamethasone will be given by oral route at 40/20 mg daily on days 1, 8, 15 and 22. The primary objective is to evaluate the MRD rate at 10-5 in patients with RRMM treated with IsKPd. Patients will pursue Isa-KPd until progression or unacceptable toxicity. Key secondary objectives include the survival analysis (OS, PFS, EFS, TTNT), response rates and duration of response and evaluation of the safety profile.
The IFM2018-03 study is currently enrolling patients in several centers in France. The study is expected to complete recruitment in 2022 and read primary end point in 2023. Clinical trial information: NCT04287855.

Disclosures: Perrot: Abbvie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Manier: AbbVie, Adaptive Biotechnology, Amgen, Celgene/BMS, GlaxoSmithKline, Janssen, Novartis, Oncopeptide, Regeneron, Roche, Takeda: Consultancy. Karlin: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial Support travel & scientific meetings; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial Support travel & scientific meetings; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene-BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Hulin: Sanofi: Honoraria; Takeda: Honoraria; GSK: Honoraria; BMS: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Decaux: Takeda: Honoraria; Sanofi: Honoraria; Gilead: Honoraria; Roche: Honoraria; BMS: Honoraria; GSK: Honoraria; Janssen: Honoraria. Vincent: Sanofi: Honoraria, Other: Financing meeting participation; Sandoz: Other: Education course paid by sandoz; Pfizer: Other: Financing meeting participation, congress participation; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Financing meeting participation; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financing meeting participation; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Financing meeting participation; Amgen: Membership on an entity's Board of Directors or advisory committees. Mohty: Oncopeptides: Honoraria; Pfizer,: Honoraria; Takeda: Honoraria; GSK: Honoraria; Adaptive Biotechnologies: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Jazz Pharmaceuticals: Honoraria, Research Funding; Celgene: Honoraria; Bristol Myers Squibb: Honoraria; Gilead: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Moreau: AbbVie, Amgen, Celgene, Janssen, Oncopeptides, Sanofi: Honoraria. Leleu: Takeda: Honoraria; BMS: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Amgen, Merck, BMS, GSK, Janssen, Oncopeptide, Takeda, Roche, Novartis, AbbVie, Sanofi, Gilead, Pfizer, Harpoon Therapeutic, Regeneron, Iteos: Consultancy, Honoraria; Amgen, BMS/Celgene, Janssen, Takeda, Novartis, Sanofi, Merck, Oncopeptide, Karyopharm, Roche, Abbvie, Carsgen, GSK, and Harpoon Therapeutics: Honoraria.

*signifies non-member of ASH