CAR T-cell therapy Carvykti shows promise in early myeloma
Treatment results seen in 17 patients in the Phase 2 CARITITUDE-2 clinical trial
A single infusion of the CAR T-cell therapy Carvykti (ciltacabtagene autoleucel) was sufficient to control disease activity in most multiple myeloma patients who hadn’t fully responded to a standard autologous stem cell transplant (ASCT).
That’s according to new data from the 17 patients in cohort D of the Phase 2 CARITITUDE-2 clinical trial (NCT04133636), which tested Carvykti in different patient groups based on previous treatments.
“We are excited to unveil these results from our CARTITUDE-2 cohort D study, which show the significant impact of Carvykti on multiple myeloma patients in the earliest treatment setting to date,” said Mythili Koneru, MD, PhD, chief medical officer of Legend Biotech, in a company press release. Legend developed Carvykti with Janssen.
The findings were shared in a presentation at the 2024 American Society of Clinical Oncology (ASCO) annual meeting, May 31-June 4, in Chicago and virtually. The talk was titled “Efficacy and safety of ciltacabtagene autoleucel [with or without] lenalidomide maintenance in newly diagnosed multiple myeloma with suboptimal response to frontline autologous stem cell transplant: CARTITUDE-2 cohort D.”
“Patients who achieve a less than complete response following ASCT may experience less durable response with future treatments,” said Melissa Alsina, MD, a study investigator at H. Lee Moffitt Cancer Center and Research Institute. “The outcomes from this study showed encouraging efficacy results and indicated the potential benefit of Carvykti in this patient population.”
“We believe CARVYKTI may produce deep and durable responses earlier in the multiple myeloma treatment paradigm, so we are conducting Phase 3 studies to determine if patients will benefit from CARVYKTI as early as frontline treatment,” Koneru said.
The studies include the CARTITUDE-5 trial (NCT04923893) and the CARTITUDE-6 study (NCT05257083), which are evaluating Carvykti in people with newly diagnosed myeloma. Both are recruiting participants at sites worldwide.
Treatment response to Carvykti
With Carvykti, a type of immune cell called T-cells are collected from a patient and engineered to be equipped with a chimeric antigen receptor, or CAR, that targets BCMA, a protein highly present in myeloma cells. The modified T-cells are then infused back into the patient, where the receptor directs them to attack and kill cells producing BCMA.
The therapy was first approved in the U.S. in 2022 for adults with relapsed or refractory multiple myeloma (RRMM) who’d received at least four lines of treatment, including an immunomodulatory agent (iMiD), a proteasome inhibitor (PI), and a CD38 inhibitor.
Carvykti’s indication was recently expanded as a second-line treatment for adults with RRMM whose disease is resistant to Revlimid (lenalidomide) and who received at least one line of treatment, including an iMiD and a PI.
In group D, 17 newly diagnosed patients had had a less than optimal response to a standard autologous stem cell transplant. Most received treatment with Revlimid along with a single Carvykti dose after the transplant.
After a median follow-up of 22 months, or nearly two years, all but one patient (94%) had a complete response to treatment. Most (80%) of the 15 patients with evaluable data were negative for minimal residual disease (MRD), that is, the small number of myeloma cells that may remain after treatment and cause a relapse.
After about 1.5 years, all these patients were still alive without any sign of disease progression. Legend didn’t provide details on the patient who failed to respond to therapy and died.
Safety data from this cohort were consistent with the known profile of Carvykti. Most patients had serious side effects such as low immune cell counts and infections.
In a separate presentation titled “Ciltacabtagene autoleucel vs standard of care in patients with functional high-risk multiple myeloma: CARTITUDE-4 subgroup analysis,” researchers shared results from 79 RRMM patients with high-risk disease who participated in the Phase 3 CARTITUDE-4 trial (NCT04181827).
The study tested Carvykti against two standard treatment regimens in more than 400 adults with myeloma who’d been given one to three lines of therapy. Previous results showed that patients given Carvykti as an earlier line of therapy were significantly less likely to have disease progression, supporting its label expansion.
All 79 patients had high-risk chromosome abnormalities, Revlimid-resistant disease, and had received one line of therapy, including a PI and an IMiD. About half were treated with Carvykti while the other half were given standard treatments.
The cell therapy was associated with a 73% lower risk of disease progression or death. Also, the Carvykti-treated patients showed consistently higher rates of overall responses (88% vs. 80%), complete response or better (68% vs. 39%), MRD negativity (65% vs. 10%), and a longer median duration of response than those on standard treatments.
At the 2024 European Hematology Association (EHA) Congress, researchers presented data from a subgroup analysis in the presentation “Ciltacabtagene autoleucel vs standard of care in lenalidomide-refractory multiple myeloma: Phase 3 CARTITUDE-4 subgroup analysis by cytogenetic risk,” which showed Carvykti’s superiority over a placebo in both high-risk and standard-risk subgroups based on chromosomal abnormalities.
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