“Lenalidomide has become a foundation of care for people with myeloma, but as its use has expanded, so has the number of patients whose disease will no longer respond to the treatment. Ciltacabtagene autoleucel has not only shown that it delivers remarkably effective outcomes compared to patients’ current options, but also that it can be used safely earlier in the treatment phase,” said ASCO Expert Oreofe Odejide, MD, ASCO Expert.
ALEXANDRIA, Va. — Ciltacabtagene autoleucel (Carvykti®), a BCMA-targeting CAR T-cell therapy, significantly slows or stops progression of multiple myeloma when compared with standard-of-care treatments among those for whom lenalidomide no longer works. The research will be presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.
Study at a Glance
Multiple myeloma that no longer responds to treatment with lenalidomide (Revlimid®)
419 people with multiple myeloma that no longer responded to lenalidomide
These results support the use of ciltacabtagene autoleucel when disease is refractory to (no longer responds to) lenalidomide as early as first relapse, in addition to the currently approved 4 lines of therapy or more.
The global, phase III CARTITUDE-4 clinical trial included 419 people with multiple myeloma who had already received one to three lines of treatment, including lenalidomide, which was no longer effective. There were 208 participants in the ciltacabtagene autoleucel arm and 211 participants in the standard-of-care treatment arm, which used either a combination of bortezomib (Velcade) pomalidomide (Pomalyst), and dexamethasone or a combination of daratumumab (Darzalex), pomalidomide, and dexamethasone.
Ciltacabtagene autoleucel is a chimeric antigen receptor (CAR) T-cell therapy. In CAR T-cell therapy, some T cells are removed from the patient’s blood and are modified in a laboratory, so they have specific proteins called receptors. The receptors allow the modified T cells to recognize the cancer cells. When the modified T cells are returned to the patient’s body, they seek out and destroy cancer cells.
After a median follow-up of 16 months, the researchers found that ciltacabtagene autoleucel reduced the risk of disease progression by 74%, compared with the standard-of-care treatments. Objective response rates, which is the percentage of patients whose cancer responded to the treatment, were 84.6% in the group assigned to ciltacabtagene autoleucel, compared with 67.3% in the group assigned to standard-of-care treatment. Those assigned to the CAR T-cell therapy also had better minimal residual disease negativity (60.6%), compared with those assigned to standard of care (15.6%). Minimal residual disease negativity indicates the percentage of patients for whom testing did not find any cancer cells remaining after treatment.
“Lenalidomide-based therapies are used extensively as frontline treatments, in both young and elderly patients and including those who are transplant-eligible and transplant-ineligible. This causes an increase in the number of cases where the disease no longer responds to lenalidomide early in the course of the disease,” said lead study author Binod Dhakal, MD, of Medical College of Wisconsin, Milwaukee, WI. “These findings show that ciltacabtagene autoleucel is highly effective in patients with lenalidomide-refractory multiple myeloma as early as after first relapse.”
Most participants (97% receiving ciltacabtagene autoleucel and 94% receiving standard of care) experienced grade 3/4 adverse events, including infections (27% vs. 25%) and low blood cell counts (94% vs. 86%), including neutropenia, thrombocytopenia, and anemia. Cytokine release syndrome, which may arise as immune cells are sent into overdrive by the treatment, developed in 76% of participants who received ciltacabtagene autoleucel. Around 5% of those receiving the CAR T-cell therapy developed immune effector cell-associated neurotoxicity syndrome (ICANS), a syndrome that affects a person’s nervous system.
About the Study
CARTITUDE-4 enrolled participants from 16 countries, including the United States, Europe, Asia, and Australia. The study participants were around 61 years of age, 55% were men, and 75% were White. It is one of only two phase III clinical trials investigating CAR T-cell therapy in the early lines of therapy for multiple myeloma. CARTITUDE-4 is the only phase III study to currently explore using CAR T-cell therapy after the first relapse of the disease.
The researchers will continue to follow the study participants to determine the long-term effects of ciltacabtagene autoleucel. Additional analyses of the data are ongoing, such as health-related quality of life, subgroup analyses, and biomarker analyses. The researchers hope to publish and present additional findings when they are available. Ciltacabtagene autoleucel is also being studied as frontline therapy in additional ongoing clinical trials.
This clinical trial was funded by Janssen Research & Development and Legend Biotech USA.
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