KEY TAKEAWAYS
- CARTITUDE-2 is a multicohort phase 2 study that assessed cilta-cel in patients with multiple myeloma who were refractory to lenalidomide and had 1-3 prior lines of therapy.
- The study’s primary endpoint was minimal residual disease (MRD) negativity at 105 by next-generation sequencing.
- Patients received a single infusion of cilta-cel at a target dose of 0.75×106 CAR+ viable T cells/kg after lymphodepletion.
- The results showed an overall response rate of 95%, with 90% of patients achieving ≥complete response and 95% achieving ≥ excellent partial response.
CARTITUDE-2 (NCT04133636) assessed cilta-cel, a BCMA-targeting CAR-T therapy, in len-refractory. Study eligibility required patients to have progressive multiple myeloma (MM) after 1-3 prior lines of therapy (LOT) that included a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD). Patients must have been refractory to lenalidomide (len) and had no prior exposure to BCMA-targeting agents. After lymphodepletion, patients were administered a single infusion of cilta-cel at a target dose of 0.75×106 CAR+ viable T cells/kg, and the safety and efficacy of cilta-cel were assessed.
The study’s primary endpoint was MRD negativity at 105 by next-gen sequencing. Patient management strategies were used to reduce MNTs risk. Other assessments included pharmacokinetic (PK) analyses, which measured the Cmax and Tmax of CAR+ T-cell transgene levels in the blood, levels of cytokine release syndrome (CRS)-related cytokines such as IL-6 over time, peak levels of cytokines by response and CRS, the association of cytokine levels with immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR+ T cell CD4/CD8 ratio by reply, CRS, and ICANS.
As of January 2022, the median follow-up of the multicohort phase 2 CARTITUDE-2 study was 17.1 months (range: 3.3-23.1). In this cohort, 20 patients (65% male) with a median age of 60 years (38-75) were administered cilta-cel. A median of 2 prior LOT had been used, and a median of 3.5 years had passed since the diagnosis of multiple myeloma (MM). Of the patients, 95% were refractory to their last LOT, and 40% were triple-class refractory. The response rate was 95%, with 90% of patients achieving ≥ complete response and 95% achieving ≥ perfect partial response. The median response time was one month (within a range of 0.7-3.3), and the median response time within 0.9-13.6 was 2.6 months. All 16 individuals with an MRD evaluation achieved MRD negative at 10-5. The median time for a response was not met. The 12-month progression-free survival rate was 75%, and the 12-month event-free rate was 79%.
95% of patients experienced CRS (grade 3/4: 10%); median time to onset was 7 days; range, 5-9); median duration, 3 days; range, 2-12). Neurotoxicity occurred in 30% of patients (5 grade 1/2 and 1 grade 3/4), while ICANS occurred in 3 patients (15%; all grade 1/2), with 1 patient experiencing facial paralysis (grade 2). No MNTs were observed, but one death due to COVID-19 was deemed treatment-related by the investigator. Additionally, two deaths occurred due to progressive disease and one due to sepsis (unrelated to treatment).
The median persistence of CAR-T cells was 153.5 days (range: 57.1-336.8), according to preliminary PK assessments of the CAR transgene performed by qPCR. The most remarkable expansion of CAR-T cells occurred at day 10.5 (range: 8.7-42.9).
Cilta-cel induced durable responses in len-refractory MM patients with prior LOT. Ongoing follow-up will provide more information on safety and efficacy. PK, cytokine, and CAR-T subset analyses are forthcoming, with further study in CARTITUDE-4.
Source: https://library.ehaweb.org/eha/2022/eha2022-congress/357819/jens.hillengass.ciltacabtagene.autoleucel.in.lenalidomide-refractory.patients.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2233%2Aot_id%3D26843%2Amarker%3D1769%2Afeatured%3D17676
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04133636
Hillengass, J.1,*; Cohen, A. D.2; Delforge, M.3; Einsele, H.4; Goldschmidt, H.5; Weisel, K.6; Raab, M.-S.7; Scheid, C.8; Schecter, J. M.9; De Braganca, K. C.9; Varsos, H.9; Yeh, T.-M.9; Mistry, P.10; Roccia, T.10; Corsale, C.9; Akram, M.11; Pacaud, L.11; Nesheiwat, T.11; Agha, M.12; Cohen, Y. C.13. CILTACABTAGENE AUTOLEUCEL IN LENALIDOMIDE-REFRACTORY PATIENTS WITH PROGRESSIVE MULTIPLE MYELOMA AFTER 1-3 PRIOR LINES OF THERAPY: CARTITUDE-2 BIOLOGICAL CORRELATIVE ANALYSES AND UPDATED CLINICAL DATA. DOI: 10.1097/01.HS9.0000846704.03590.a5
