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Efficacy and Safety of Cilta-Cel in Patients with Progressive Multiple Myeloma after Exposure to Non-Cellular Anti-BCMA Immunotherapy

2022; Elsevier BV; Volume: 140; Issue: Supplement 1 Linguagem: Inglês

10.1182/blood-2022-158563

1528-0020

Adam D. Cohen, María‐Victoria Mateos, Yaël Cohen, Paula Rodríguez‐Otero, Bruno Paiva, Niels W.C.J. van de Donk, Thomas G. Martin, Attaya Suvannasankha, Christina Corsale, Jordan M. Schecter, Kevin C. De Braganca, Carolyn C. Jackson, Helen Varsos, William Deraedt, Tito Roccia, Pankaj Mistry, Xiaoying Xu, Katherine Li, Enrique Zudaire, Muhammad Akram, Lida Pacaud, Irit Avivi, Jesús F. San Miguel,

Protein Degradation and Inhibitors

Introduction: With the availability of multiple therapy classes targeting BCMA for multiple myeloma (MM), data are needed to understand effective treatment (tx) sequencing. CARTITUDE-2 (NCT04133636) is a phase 2, multicohort study evaluating the efficacy and safety of cilta-cel, an anti-BCMA CAR-T therapy, in several MM patient populations. We present updated results with a longer follow-up on cohort C patients with previous exposure to a non-cellular anti-BCMA immunotherapy. Methods: Cohort C patients had progressive MM after tx with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and non-cellular BCMA-targeting agent. A single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg) was administered 5-7 days post lymphodepletion. The primary endpoint was minimal residual disease (MRD) negativity at 10-5. Secondary endpoints included overall response rate (ORR; assessed by IMWG criteria), duration of response (DOR), and adverse events (AEs). Results: As of June 1, 2022, 20 patients (13-ADC exposed; 7 BsAb exposed; 1 patient in the ADC group also had prior BsAb exposure) were treated with cilta-cel. Four patients did not receive cilta-cel due to either low cellular yield (n=2, 1 patient in each group) or death due to progressive disease (PD) prior to dosing (n=2, 1 patient in each group). Six patients (30%) received anti-BCMA tx as their last line of therapy (LOT; n=4 ADC, n=2 BsAb). During prior anti-BCMA tx, best responses included very good partial response (VGPR; 2 patients in ADC group, 1 patient in BsAb group), stringent complete response (sCR, 1 patient in ADC group), and complete response (CR; 1 patient in BsAb group); the rest had best response of stable disease (SD) or PD (1 patient was not evaluable [NE]). At baseline, median age was 62.5 y (range, 44-81), 60% were male, 3 (15%) had high risk cytogenetics (all del17p), and 5 (25%) had baseline extramedullary disease. Patients had received a median of 8 (range, 4-13) prior LOT; 18 (90%) were triple-class refractory, 11 (55%) penta-drug refractory, and 16 (80%) refractory to non-cellular anti-BCMA treatment (Figure 1A). The median time from last anti-BCMA agent to cilta-cel infusion was 195 d (range, 62-749). Median administered dose of cilta-cel was 0.65x106 (range, 0.21x106- 1.11x106) CAR+ viable T cells/kg; 1 patient received a below-target dose. At a median follow-up of 18.0 mo (range, 0.6-22.7), 7 of 10 evaluable patients (70%) were MRD-negative at 10-5 (5 of 7 evaluable patients [71.4%] in the ADC group, and 2 of 3 evaluable patients [66.7%] in the BsAb group). The ORR was 60% (95% CI, 36.1 - 80.9) for the full cohort (61.5% [95% CI, 31.6-86.1] in the ADC group and 57.1% [95% CI, 18.4-90.1] in the BsAb group; Figure 1B). Median DOR (95% CI) was 12.8 mo (7.9-NE) in the full cohort, 12.8 mo (7.9-NE) in the ADC group, and 8.2 mo (4.4-NE) in the BsAb group. Median PFS (95% CI) was 9.1 (1.5-13.8) mo in the full cohort, 9.5 mo (1.0-15.2) in the ADC group, and 5.3 mo (0.6-NE) in the BsAb group. Patients who responded to cilta-cel had a shorter median duration of last anti-BCMA agent exposure (29.5 d, range 1-277) compared with non-responders (63.5 d, range 54-260). Responders also had a longer median time from last anti-BCMA tx exposure to apheresis (161.0 d, range 26-695) than non-responders (56.5 d, range 40-77). The most common AEs were hematologic. CRS occurred in 12 (60%) patients (all grade 1/2), with median time to onset of 7.5 d (range, 2-10) and median duration of 6.0 d (3-10). ICANS occurred in 4 (20%) patients (2 grade 3/4), with median time to onset of 9.0 d (range, 4-13) and median duration of 7.0 d (range, 4-20). ICANS was recovered or resolved in 3 patients. No patient had movement or neurocognitive tx emergent AE/parkinsonism. There were 12 deaths: 8 due to PD, 2 due to COVID-19 pneumonia (not tx related), and 1 each due to subarachnoid hemorrhage (not tx related) and C. difficile colitis (tx related). Conclusions: Heavily pretreated MM patients with previous exposure to a non-cellular anti-BCMA therapy had favorable responses following cilta-cel. However, depth and DOR appear lower than that seen in anti-BCMA-naïve patients treated with cilta-cel (at 27.7 mos, median DOR was not reached in heavily pre-treated but anti-BCMA naïve CARTITUDE-1 patients). These results may inform tx plans, including sequencing and washout period between BCMA-targeting agents. Figure 1: (A) Patient Demographics and Disease Characteristics, (B) ORR Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal