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207 Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone Induction and Consolidation with Tandem Transplant in High-Risk Newly Diagnosed Myeloma Patients: Final Results of the Phase 2 Study IFM 2018-04Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Multiple Myeloma: Prospective Therapeutic Trials: Smoldering and Newly Diagnosed Myeloma
Hematology Disease Topics & Pathways:
Therapies, Minimal Residual Disease
Saturday, December 9, 2023: 2:30 PM

Cyrille Touzeau, MD, PhD1*, Aurore Perrot, MD, PhD2*, Cyrille Hulin, MD3*, Salomon Manier, MD, PhD4, Margaret Macro, MD5*, Marie-Lorraine Chretien, MD6*, Lionel Karlin7*, Olivier Decaux, MD, PhD8*, Caroline Jacquet, MD9*, Mourad Tiab, MD10*, Xavier Leleu, MD11, Jill Corre, PharmD, PhD12*, Alexandra Jobert13*, Lucie Planche14*, Herve Avet-Loiseau, MD, PhD15* and Philippe Moreau, MD, PhD16*

1Centre Hospitalier Universitaire de Nantes, Nantes, France
2Toulouse, and CRCT, Toulouse, France, Toulouse, France
3Centre Hospitalier Universitaire de Bordeaux, Pessac Cedex, FRA
4Centre Hospitalier Universitaire - Hôpital Huriez, Lille, France
5Hopital Cote De Nacre, Caen, France
7CH Lyon Sud, Pierre Benite Cedex, FRA
8Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou, Rennes, France
9CHU de Nancy, Vandoeuvre Les Nancy, FRA
10Centre Hospitalier Departemental, La Roche Sur Yon Cedex 9, FRA
11Service D'Hématologie Et Thérapie Cellulaire, Poitiers, France
12Institut universitaire du cancer de Toulouse Oncopole,, Toulouse, France
13Centre Hospitalier Universitaire, Nantes, France
14Chu Nantes, Nantes, FRA
15Institut universitaire du cancer de Toulouse Oncopole, Toulouse, France
16Hematology Clinic, University Hospital Hotel-Dieu, Nantes, France

Background: High-risk (HR) cytogenetic is associated with poor outcome in transplant eligible (TE) newly diagnosed multiple myeloma (NDMM). The triplet combination carfilzomib lenalidomide and dexamethasone (KRD) plus transplantation demonstrated high efficacy with favorable safety profile in TE-NDMM patients (FORTE). The addition of daratumumab (Dara) to frontline therapy also improved response rate and progression free-survival in TE-NDMM patients (CASSIOPEIA, GRIFFIN). Double transplant also improved outcome of HR TE NDMM patients (EMN02). The phase 2 trial 2018-04 from the Intergroupe Francophone du Myelome (IFM) evaluated an intensive strategy with Dara-KRD induction and consolidation plus double transplant in HR TE NDMM (NCT03606577).

Methods: HR MM was defined by the presence of del17p, t(4;14) and/or t(14;16). Treatment strategy included Dara-KRD induction (6 cycles), autologous stem cell transplantation (ASCT), Dara-KRD consolidation (4 cycles), second ASCT, Dara-lenalidomide maintenance for 2 years. The primary endpoint was the feasibility of this intensive strategy.

Results: Fifty patients with previously untreated NDMM were included from july 2019 to march 2021 in 11 IFM centers. Median age was 57 (range 38 -65). Based on inclusion criteria, all patients had HR cytogenetic, including 17p deletion (n=20, 40%), t(4;14) (n=26, 52%) or t(14;16) (n=10, 20%). Four (8%) patients had extramedullary disease. At data cut-off, the study met the primary endpoint with 36 (72%) patients completing second transplant. Twenty-one patients (42%) discontinued the study, due to stem-cell collection failure (n=8), disease progression (n=8), adverse event (n=4), consent withdrawal (n=1). Grade 3-4 Dara-KRD induction/consolidation related adverse event (>5% of patients) were neutropenia (44%), anemia (22%), thrombocytopenia (24%) and infection (14%). Four patients discontinued treatment due to severe adverse event (COVID-19 infection, drug-induced hepatitis, JC virus related encephalopathy, intracerebral hemorrhage). Seven patients died, 5 due to disease progression and 2 due to infection. Responses deepened over time with an overall response rate before maintenance of 100%, including 81 % complete response. Among evaluable patients (33/36), pre maintenance Minimal Residual Disease negativity rate (NGS, 10-6) was 94%. After a median follow up of 32 months, the 24-months PFS is 87% (78-87%) and the 24-months OS is 94% (87-100%).

Conclusions: Dara-KRD induction/consolidation with tandem transplant was feasible in TE NDMM patients with high-risk cytogenetic profile, and resulted in high MRD negativity rate and high progression free survival.

Disclosures: Touzeau: Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Perrot: AbbVie: Honoraria; Takeda: Honoraria, Research Funding; Pfizer: Honoraria; Adaptive Biotechnologies: Honoraria; Sanofi: Honoraria, Research Funding; Amgen: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding; Janssen: Honoraria. Hulin: Amgen: Honoraria; Sanofi: Honoraria; AbbVie: Honoraria; Pfizer: Honoraria; Janssen: Honoraria; Bristol Myers Squibb: Honoraria. Manier: Janssen: Consultancy; BMS: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Abbvie: Consultancy; Regeneron: Consultancy; Roche: Consultancy; Sanofi: Consultancy. Macro: Janssen, Takeda: Honoraria, Other: Travel/accommodation, Research Funding; GSK, Sanofi: Honoraria. Karlin: AbbVie, Amgen, Celgene, Janssen, Sanofi, Takeda: Honoraria; Amgen, Celgene, GSK, Janssen, Takeda: Consultancy. Decaux: Janssen, BMS, GSK, Sanofi, Takeda, Roche, Gilead: Honoraria. Leleu: AbbVie: Honoraria; GSK: Honoraria; Merck: Honoraria; Harpoon Therapeutics: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Amgen: Honoraria; BMS/Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Moreau: janssen, celgene BMS, abbvie, sanofi, amgen, takeda, pfizer: Honoraria, Other: advisory boards; GSK: Honoraria, Other: Advisory Board.

*signifies non-member of ASH