Newly approved myeloma treatment found highly effective in first real-world patient population
CANCER DIGEST – Oct. 6, 2024 – In a first test of more typical patients with multiple myeloma, a newly FDA-approved drug proved nearly as effective as it did in the phase II clinical trial that led to its approval for clinical use.
The significance of the new study is that it shows the newly approved drug is nearly as highly effective in a patient population that is more typical of what is seen by oncologists in everyday cancer settings as it was in patients carefully selected for the trial that led to its approval. The early clinical trial involved patients who were generally in better health in terms of performance status, blood counts, and organ function, than what is typically seen across the spectrum of these patients.
Multiple myeloma is a blood cancer that results in over production of abnormal plasma cells that build up in the bone marrow and crowd out production of a number of other blood cells that fight infections and abnormal cells. According to the American Cancer Society about 35,000 people in the US are diagnosed with multiple myeloma each year.
The new drug is called ciltacabtagene autoleucel or cilta-cel. It is a chimeric antigen receptor (CAR), an engineered protein that helps T-cells identify and attack cancer cells. CAR T-cell immunotherapy has proven very effective for some people with certain cancers.
Much ongoing research, including this study, is aimed at expanding the number of people for whom CAR T-cell therapy is effective. Typically the therapy involves identifying T-cells in the patient’s immune system that already attack the cancer, removing some of those cells, and adding these CAR proteins to make the T-cells more effective, and then growing billions of them in the laboratory for reinfusion into the patient.
In the case of cilta-cel CAR T-cell therapy, the early small clinical trial that led to FDA-approval involved optimally selected patients who underwent the therapy for their multiple myeloma. The results of that trial showed that in 98 percent of patients treated, the multiple myeloma responded to the treatment and 83 percent had a complete response, meaning the cancer disappeared.
In the current larger clinical trial, patient eligibility more closely matched real world make-up of multiple myeloma patients. It involved 255 patients who had undergone a median of six prior lines of treatment without seeing a lasting response.
Of those who started the cilta-cel CAR T-cell therapy 92 percent were able to complete the full therapy. Among the patients who received the CAR T-cell product within the range specified by the FDA, 94 percent experienced a response and 76 percent saw a complete response compared to 20 percent of patients whose CAR T-cells did not fully meet the FDA specifications.
The study found that three-quarters of those who received cilta-cel infusions experienced cytokine release syndrome (CRS), a common CAR T-cell side effect resulting from a stronger than expected immune response that can cause fevers, severe nausea, dizziness, fatigue, and muscle or joint pain. Of those patients experiencing CRS, however, only 5 percent experienced events of grade 3 or higher.
Overall, 14 percent of study participants experienced neurotoxicity, such as confusion, memory loss, or muscle weakness, and 2 percent experienced experienced Parkinsonism, a condition that mimics Parkinson’s disease symptoms such as rigidity and tremors.
Overall, deaths not due to cancer reached 10 percent and was higher compared to similar clinical trials due to infections or CRS, suggesting that more attention to infections and CRS might reduce that rate.
The authors of the study caution that this was a retrospective study, meaning it used data collected and analyzed from previous clinical trials without a control group. Consequently the researchers call for additional studies to find ways to reduce the side effects and determine whether treatment with cilta-cel infusion earlier in the patient’s cancer might reduce toxicity.
Sources: American Society of Hematology (ASH) press release
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