CARTITUDE-4 Data Leak Reveals Promising Results for Cilta-Cel in Multiple Myeloma


The CAR-T therapy reduced disease progression risk by 74%, according to a data leak reported by STAT News. The data are expected to be presented on May 11 at the 2023 European Hematology Association Congress.

Brian Kenney, the global therapeutic area and cross-sector oncology communication leader for Janssen R&D and Johnson & Johnson External Innovation

Brian Kenney

Among individuals with relapsed and lenalidomide-refractory multiple myeloma (MM), ciltacabtagene autoleucel (Carvykti; Johnson & Johnson/Legend Biotech) has outperformed expectations compared with standard chemotherapy regimens—such as pomalidomide, bortezomib and dexamethasone; or daratumumab, pomalidomide and dexamethasone—according to leaked data from the phase 3 CARTITUDE-4 trial (NCT04181827) obtained by STAT News.1

Based on the data that were obtained, those treated with the chimeric antigen receptor T-cell (CAR-T) therapy—also known as cilta-cel—reported a 74% reduction in the risk of disease progression compared with standard regimens. Additionally, Carvykti is reported to have cut the mortality risk by 22% relative to standard chemotherapy, though this effect appears to have been deemed not statistically significant.1

There has been some suggestion that if positive findings such as these are confirmed, the treatment could possibly be considered for first-line therapy, which would prove to be a paradigm-shifting approach to care. The data are expected to be presented to the public early next month, on May 11, at the annual European Hematology Association Congress, and then a few weeks later, on May 25, at the American Society of Clinical Oncology (ASCO) annual meeting. The trial has an estimated completion date of April 10, 2026.

In January 2023, Johnson & Johnson and Legend Biotech announced that the Independent Data Monitoring Committee for CARTITUDE-4 had recommended an unblinding of the trial after the treatment met the primary end point—progression-free survival (PFS)—but no data were shared.2 All in all, the trial enrolled 419 patients aged 18 years and older who had received between 1 and 3 prior lines of therapy for MM, including a proteasome inhibitor and an immunomodulatory drug. The trial’s various secondary end points include complete response rate, overall minimal residual disease negative rate, overall survival, overall response rate, time to worsening of symptoms, and incidence and severity of adverse events.

READ MORE: Afami-cel Prompts Antitumor Immune Response in Synovial Sarcoma, Myxoid/Round Cell Liposarcoma

As for safety, STAT reported that serious adverse events (AEs) occurred in 97% of cilta-cel–treated patients, including 76% of those with immune-related AEs. There were no data regarding treatment-related deaths included in the report.

Cilta-cel is an autologous immunotherapy that genetically modifies T-cells to encode for CAR-Ts. These receptors seek out and bind to the B-cell maturation antigen (BCMA) protein, which activates T-cells and promotes antitumor activity. The treatment was initially approved by the FDA in March 2022 to treat patients with relapsed or refractory MM who had undergone and failed 4 or more prior lines of therapy. That approval was supported by efficacy data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207), in which cilta-cel elicited an objective response rate (ORR) of 98% (95% CI, 92.7%-99.7%) in this patient population, as well as a complete response rate of 78% (95% CI, 68.8%-86.1%). The median duration of response was 21.8 months at a median 18 months of follow-up.3

These promising leaked data may pose a shift toward the positive for cilta-cel, as the leak follows a recent announcement that Janssen Biotech, of Johnson & Johnson, would be withdrawing its UK application for approval to the UK’s National Institute of Health and Care Excellence (NICE), which was reported by the charity group Myeloma UK in March.4 That decision, though, appears to be related to production issues that have affected the ability of manufacturers to meet the demand for CAR-T therapies. Myeloma UK noted that manufacturing issues have affected the availability of CAR-T therapies developed by other companies, including Bristol Myers Squibb’s ide-cel.

At the time, Brian Kenney, the global therapeutic area and cross-sector oncology communication leader for Janssen R&D and Johnson & Johnson External Innovation, said in a statement issued to CGTLive that, “Janssen agreed with NICE to withdraw the assessment of cilta-cel in the UK for the treatment of heavily pre-treated patients with multiple myeloma. Despite our efforts and commitment to advancing this cell therapy for patients and physicians, we are not currently in a position to progress through the NICE appraisal process.”

“While the withdrawal means that patients will not be able to access cilta-cel through the National Health Service at this time, the clinical trial program in the UK is not impacted by this development,” Kenney added. “We recognize the high unmet need of patients with multiple myeloma and remain committed to bringing CAR-T therapy to the multiple myeloma community.”

1. Feuerstein A. Leaked study results show a CAR-T from J&J providing big benefit for patients with multiple myeloma. STAT. April 19, 2023. Accessed April 19, 2023.
2. Janssen Announces Unblinding of Phase 3 CARTITUDE-4 Study of CARVYKTI® (cilta-cel) as Primary Endpoint Met in Treatment of Patients with Relapsed and Refractory Multiple Myeloma. News release. Johnson & Johnson. January 27, 2023. Accessed April 19, 2023.
3. Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314-324. doi:10.1016/S0140-6736(21)00933-8
4. Pharmaceutical company halts access to CAR-T cell treatment for UK myeloma patients. News release. Myeloma UK. March 13, 2023. Accessed April 19, 2023.
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