A final analysis of data from CARTITUDE-1 was also presented at SOHO 2023, which revealed a PFS of 24.9 months in treated patients.
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Patients with heavily pretreated relapsed/refractory multiple myeloma (MM) treated with ciltacabtagene autoleucel (cilta-cel; Carvykti) that had minimal residual disease (MRD) negativity sustained for 6 months or longer had longer duration of responses (DOR) and progresion-free survival (PFS) compared with those who had MRD negativity sustained for less than 6 months, according to a new analysis from the phase 1b/2 CARTITUDE-1 study (NCT03548207).
The new data were presented at the 2023 Society of Hematologic Oncology (SOHO) 11th Annual Meeting, held September 6-9 in Houston, Texas, by Yi Lin, MD, PhD, a hematologist and oncologist at Mayo Clinic.
“Patients who are able to achieve sustained MRD-negativity for at least 6 months or longer are the patients who were able to achieve the deepest and best response, had the longest duration of response, as well as PFS,” Lin said during an oral abstract presentation of the results at the SOHO meeting.
Cilta-cel was approved by the FDA in February 2022 for the treatment of adult patients with relapsed or refractory MM after 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This approval was based on findings from the open-label CARTITUDE-1 study.
CARTITUDE-1 treated 97 patients with a single infusion of cilta-cel at a target dose of 0.75 x 106 CAR-positive cells per kg after conditioning therapy with cyclophosphamide at 300 mg/m2 and fludarabine at 30 mg/m2 5 and 3 days before infusion. Participants had a median of 6 prior lines of therapy (range, 3-18) and almost all (99%) were refractory to their last line of therapy. Of those enrolled, 42% were penta-drug refractory and 88% were triple-class refractory.
The final analysis of CARTITUDE-1, also presented at the SOHO meeting, revealed that median PFS with cilta-cel was 34.9 months.2 The objective response rate (ORR) was 97.9%, which included a stringent complete response (sCR) for 82.5% of patients treated with the CAR T cells. The median duration of response was 33.9 months and the overall survival had not yet been reached, with nearly two-thirds of patients still alive at a 3-year follow up (62.9%).
Of the responses, 61 were evaluable for MRD at any point, with 56 of these patients (91.8%) testing negative for MRD with a threshold of 10-5. Overall, there were 22 patients who were MRD-negative for less than 6 months and 34 patients who were MRD-negative for 6 months or longer. Of these patients, 10 were MRD-negative for 6 to 12 months and 24 were negative for 12 months or longer.
Baseline characteristics did not vary significantly between those with a sustained MRD-negative response and those without, although there was an insignificant trend toward longer time since diagnosis in those with a sustained MRD-negative response of 12 months or longer, Lin noted. In those with an MRD-negative response of less than 6 months, the median time from diagnosis was 4.8 months (range, 1.6-16.3). In those with an MRD-negative response that was sustained for 12 months or longer, the median time since diagnosis was 7.0 years (range, 2.5-18.2).
There was also a trend toward those with fewer plasmacytomas having a longer MRD-negative response, but these numbers were small, Lin cautioned. Overall, 27.3% of those who were MRD-negative for less than 6 months had plasmacytomas (n = 6) compared with 20% (n = 2) and 8.3% (n = 2) in the 6- to 12- and 12- or more month groups, respectively.
An sCR was achieved by all patients with a sustained response of 6 months or longer. In those with an MRD-negative response of less than 6 months, the CR rate was 55%, the very good partial response rate was 36%, and the partial response rate was 5%. There was 1 patient without a defined response for an ORR of 95% in this group.
The median DOR was not yet evaluable for those in the sustained MRD-negative groups. In the group that was MRD-negative for 6 months or less, the median DOR was 10.3 months (95% CI, 5.1-15.6). Similarly, median PFS was not available for those with a sustained response. In those with MRD for less than 6 months, the median PFS was 11.0 months (95% CI, 5.4-16.6).
Other characteristics of response to cilta-cel are under exploration, including the expansion and proliferation of the cells in vivo. In the study, only a portion of patients were assessable for MRD, and having a proxy like cell expansion could serve as a useful marker of depth of response, suggested session moderator Thomas G. Martin, MD, associate director of the UCSF Helen Diller Family Comprehensive Cancer Center myeloma program. “There are some patients who receive cilta-cel and by day 15 their white [blood cell] count is 30,000 and it is 28% lymphocytes,” he said. “The question is whether those are the same patients who achieve MRD, and that would be awesome to know.”