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3390 Updated Comparative Efficacy of Ciltacabtagene Autoleucel Versus Idecabtagene Vicleucel in Patients with Relapsed or Refractory Multiple Myeloma Previously Treated with 2–4 Prior Lines of Therapy Using a Matching-Adjusted Indirect Comparison

Program: Oral and Poster Abstracts
Session: 655. Multiple Myeloma: Cellular Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Health outcomes research, Clinical Research, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Biological therapies, Treatment Considerations, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Nieves Lopez-Muñoz1*, Noffar Bar, MD2, Joris Diels3*, Suzy van Sanden3*, João Mendes4*, Seina Lee4*, Teresa Hernando5*, Nikoletta Lendvai6*, Nitin Patel7*, Tadao Ishida8, Jeremy Er9, Simon J Harrison, MBBS, PhD10 and Urvi A. Shah, MD11

1Hospital Universitario 12 de Octubre, Madrid, Spain
2Department of Internal Medicine, Section of Hematology, Yale University School of Medicine and Yale Cancer Center, New Haven, CT
3Janssen Pharmaceutica NV, Beerse, Belgium
4Janssen Global Services, LLC, Raritan, NJ
5Janssen-Cilag, Madrid, Spain
6Oncology Clinical Development, Johnson and Johnson Innovative Medicine, Bridgewater, NJ
7Legend Biotech USA Inc., Somerset, NJ
8Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan
9Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
10Clinical Haematology and Centre of Excellence for Cellular Immunotherapy, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia
11Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY

Introduction:

Two novel B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor T-cell (CAR-T) therapies, ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma) were initially approved for heavily pre-treated relapsed/refractory multiple myeloma (RRMM) based on the CARTITUDE-1 and KarMMa-1 studies. An extension of indication has been recently approved by the FDA and EMA (2024) for the treatment of adult patients with RRMM who have received at least 1 prior line of therapy (LOT), including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), and are refractory to lenalidomide (cilta-cel; CARTITUDE-4); and in patients with RRMM after 2 or more prior LOT, including an IMiD, a PI, and an anti-CD38 monoclonal antibody (ide-cel; KarMMa-3). In the absence of a head-to-head comparison of these two therapies, an unanchored matching-adjusted indirect comparison (MAIC) was used to estimate their relative efficacy using data from CARTITUDE-4, CARTITUDE-1, and KarMMa-3. Since the initial publication of this MAIC, data from longer follow-ups became available for both CARTITUDE-4 and KarMMa-3, reporting overall survival (OS) outcomes, allowing for an updated assessment of the comparative efficacy between cilta-cel and ide-cel.

Methods:

While both KarMMa-3 and CARTITUDE-4 included DPd in the physician’s choice control arm, no data were published on this subgroup from KarMMa-3, which could be used as common arm in anchored indirect comparisons between both studies. Therefore, an unanchored MAIC was performed utilizing individual patient-level data (IPD) from all apheresed patients from the cilta-cel arms (N=245), including 208 patients from CARTITUDE-4 who had received 1–3 prior LOT and 37 patients from CARTITUDE-1 with 3–4 prior LOT. From this cohort, cilta-cel patients who fulfilled the inclusion criteria from KarMMa-3 (2–4 prior LOT and triple-class exposed) were selected, and their outcomes were compared against published summary data for ide-cel (N=254) from KarMMa-3 using reconstructed IPD for response endpoints and simulated IPD from published Kaplan–Meier (KM) curves for progression-free survival (PFS) and OS. Further imbalances in patient characteristics were adjusted for by weighting the cilta-cel IPD to match the reported baseline characteristics of KarMMa-3 in terms of refractory status, R-ISS stage, time to progression on prior LOT, cytogenetic risk, and presence of extramedullary disease. Comparative efficacy was estimated for overall response rate (ORR), very good partial response or better (≥VGPR) rate, complete response or better (≥CR) rate, PFS and OS. For binary endpoints, relative effects were quantified using relative response ratios (RRs) with 95% confidence intervals (CIs) derived from a weighted logistic regression analysis. For PFS and OS, the hazard ratio (HR) with 95% CIs for cilta-cel versus ide-cel was estimated using a weighted Cox proportional hazards model.

Results:

After applying the KarMMa-3 inclusion and exclusion criteria to the CARTITUDE-1 and CARTITUDE-4 IPD (excluding patients with only 1 prior LOT or no prior daratumumab), 36 patients and 49 patients were included from the cilta-cel trials, respectively. After adjustment, patients in the cilta-cel group (effective sample size [ESS]=41) were significantly more likely to achieve an overall response (RR: 1.20 [95% CI: 1.06, 1.36]; p=0.0167), and to reach deeper levels of response as demonstrated by ≥VGPR (RR: 1.36 [95% CI: 1.18, 1.57]; p= 0.0010), and ≥CR (RR: 1.79 [95% CI: 1.48, 2.17]; p<0.0001) compared to the ide-cel patients. In addition, a statistically significant reduction of 56% in the risk of disease progression or death was observed with cilta-cel versus ide-cel (HR: 0.44 [0.27, 0.70], p=0.0007) as well as a 40% reduction for the risk death (HR: 0.60 [0.35, 1.02], p=0.06).

Conclusions:

This unanchored MAIC demonstrated clinical benefit of cilta-cel over ide-cel across response outcomes, PFS and OS for patients with triple-class exposed RRMM treated with 2–4 prior LOT. These results are consistent with previously published comparative results between both CAR-T treatments, and the new OS results highlight the added value of cilta-cel in this patient population. These comparisons provide valuable information to contextualize the efficacy of cilta-cel compared to ide-cel for the treatment of multiple myeloma.

Disclosures: Diels: J&J Innovative Medicine: Current Employment. van Sanden: J&J Innovative Medicine: Current Employment, Current equity holder in publicly-traded company. Mendes: Johnson & Johnson: Current Employment. Lee: Janssen: Current Employment, Current equity holder in publicly-traded company. Hernando: Janssen: Current Employment, Current equity holder in publicly-traded company. Lendvai: Johnson and Johnson Innovative Medicine: Current Employment, Current equity holder in publicly-traded company. Patel: Legend Biotech, GSK, Freeline, BMS (spouse), AbbVie (spouse): Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Er: Abbvie: Patents & Royalties. Harrison: Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Haematologix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Eusa: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Shah: Sanofi: Honoraria; Bristol Myers Squibb: Research Funding; Janssen: Honoraria, Research Funding.

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