French Early Nationwide Idecabtagene Vicleucel (Ide-Cel) Chimeric Antigen Receptor (CAR) T-Cell Therapy Experience in Patients with Relapsed/Refractory Multiple Myeloma (FENIX): An IFM Study from the Descar-T Registry

Introduction Prognosis of patients with relapsed/refractory multiple myeloma (RRMM) is poor, particularly in triple-class refractory patients (refractory to a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody). Idecabtagene vicleucel (Ide-Cel) is the first chimeric antigen receptor (CAR) T-cell therapy targeting the B-cell maturation antigen (BCMA) approved by both the European Medicines Agency and the US FDA and has been available in France through the Early Access Program for treatment (≥ 3 lines) of RRMM since June 2021. Approval was granted based on data from the KarMMa phase 2 trial including 54 patients receiving the approved dose that showed a response rate of 81%, complete response (CR) or better in 39% of patients, and an estimated median progression-free survival (PFS) of 12.1 months. However, up to now, real-world data are missing. In France, all patients treated with CAR T-cells including Ide-cel are consecutively enrolled in the DESCAR-T registry and clinical/biological data are directly collected from medical records which can be correlated with outcomes.

Methods We conducted a multicenter, retrospective, observational study that included all consecutive patients with RRMM treated with Ide-Cel in France up to March 2022 who were registered in the DESCAR-T database of patients treated with CAR T therapy. The main objective was to analyze efficacy in terms of response rates: overall response rate (ORR), partial response (PR), very good PR (VGPR), CR, PFS and overall survival (OS). Secondary objectives included evaluation of safety in terms of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenia and infection.

Results From June 2021 to December 2021, 53 patients were registered in DESCAR-T and underwent leukapheresis to be treated with Ide-cel, 49 (92%) were infused; 4 were not infused due to rapidly progressive disease and worsening clinical conditions. Median age of the 53 patients was 61 years (range 42-77), 66% were male, median number of prior treatment lines was 5 (range 2-8) including prior autologous stem cell transplantation (ASCT) in 49 (93%); 46 (87%) were triple-refractory, 38 (72%) were penta-refractory. At diagnosis, 6/33 (18%) had R-ISS stage III disease.

Regarding high-risk cytogenetic abnormality, 9/34 had a del(17p), 6/36 had t(4;14), and 13/50 (26%) had extramedullary disease. Fourteen (26%) patients did not meet KarMMa inclusion criteria: cytopenia (n=4), kidney failure (n=3), performance score (PS) >1 (n=2), prior anti BCMA drug conjugate antibody (n=3), prior allograft (n=2).

Forty-seven (89%) received bridging therapy of which 14 (30%) responded (13 PR; 1 VGPR). All patients received fludarabine-cyclophosphamide as the lymphodepletion regimen. Median time from apheresis to infusion was 64 days (range 51-131).

Among the 49 infused patients, median follow-up after infusion was 4.2 months. At month (M)1, ORR was 88% (n=43) with 11 (23%) CR, 9 (19%) VGPR and 23 (47%) PR. At M3, ORR was 76% (n=34/45) with 3 (7%) SCR, 15 (33%) CR, 9 (20%) VGPR and 7 (16%) PR. Eighteen of 39 (46%) patients with non-progressive disease at M1 deepened their response at M3: 8 achieved CR (PR to CR n=5, VGPR to CR n=3). The 3-month PFS rate was 82% and OS at 3 months was 93%.

CRS occurred in 45 (92%) patients, with 90% occurring within the first two days and only 1 case had severe (grade ≥ 3) CRS. ICANS occurred in 8 (16%) patients (3 with grade ≥ 3); 31 (63%) patients received tocilizumab, and 12 (24%) received steroids.

Persistent cytopenia at M1 was observed in 35 (71%) patients with grade ≥ 3 thrombocytopenia, anemia and neutropenia in 17 (35%), 6 (12%) and 23 (47%) patients, respectively.

Grade ≥ 3 infections were observed in 8 (16%) patients during the first month after infusion, including one patient with mucormycosis.

At data cut-off, 8 patients died: 2 of acute toxicity (1 sepsis and 1 severe bleeding) and 6 of disease progression.

Conclusion This study is the first European real-world multicenter retrospective study evaluating safety and efficacy of Ide-cel in patients with RRMM. Response rates and safety were comparable to those reported in the registration trial. Twenty-six percent of patients would not have been eligible for the KarMMa study and 72% were penta-refractory as compared to 15% in the "450x10^6” cohort in the KarMMa study. Longer follow-up and additional data will be presented at the ASH meeting.

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. Touzeau:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Leleu:Sanofi: Honoraria; Amgen: Honoraria; Janssen: Honoraria; BMS: Honoraria; Takeda: Honoraria; Amgen, Merck, BMS, GSK, Janssen, Oncopeptide, Takeda, Roche, Novartis, AbbVie, Sanofi, Gilead, Pfizer, Harpoon Therapeutic, Regeneron, Iteos: Consultancy, Honoraria; Pfizer: Honoraria; Amgen, BMS/Celgene, Janssen, Takeda, Novartis, Sanofi, Merck, Oncopeptide, Karyopharm, Roche, Abbvie, Carsgen, GSK, and Harpoon Therapeutics: Honoraria. Perrot:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; 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. Bories:Novartis, Kite/Gilead, BMS-Celgene, Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Vincent:BMS: 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; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Financing meeting participation; Sanofi: Honoraria, Other: Financing meeting participation; Pfizer: Other: Financing meeting participation, congress participation; Sandoz: Other: Education course paid by sandoz; Amgen: Membership on an entity's Board of Directors or advisory committees. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding; Amgen: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Adaptive Biotechnologies: Honoraria; Oncopeptides: Honoraria; Pfizer,: Honoraria; GSK: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria. Malard:Therakos/Mallinckrodt: Honoraria; Sanofi: Honoraria; Astellas: Honoraria; JAZZ pharmaceuticals: Honoraria; Biocodex: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Gilead: Honoraria; Celgene-BMS: Honoraria. Yakoub-Agha:Bristol Myers Squibb: Honoraria; Janssen: Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Brisou:Incyte: Honoraria; Gilead: Honoraria; BMS: Honoraria; Novartis: Honoraria. Decaux:Gilead: Honoraria; Roche: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; GSK: Honoraria; BMS: Honoraria; Janssen: Honoraria. Houot:Kite/Gilead, Novartis, BMS/Gelgene, ADC THerapeutics, Incyte, Miltenyi: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead, Novartis, Incyte, Janssen, MSD, Takeda, Roche: Honoraria. Le Gouill:Novartis, Kite/Gilead, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support. Moreau:AbbVie, Janssen, Celgene, Amgen, and Sanofi: Honoraria. Arnulf:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: 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; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; GSK: Membership on an entity's Board of Directors or advisory committees.