The incidence of secondary primary malignancies (SPMs) that occurred in cancer survivors after receiving CAR T-cell therapy was statistically comparable to the incidence of SPMs after other standard therapies, according to a systematic review and meta-analysis.
Journal where study was published: Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR)
Author: Kai Rejeski, MD, a visiting scientist and research fellow in the Department of Adult Bone Marrow Transplantation at Memorial Sloan Kettering Cancer Center.
Background: In January 2024, the U.S. Food and Drug Administration (FDA) required that the labeling for all currently available CAR T-cell therapies include a boxed warning to alert prescribers and patients to the potential risks of secondary cancer after CAR T-cell therapy. The boxed warnings specifically alert patients to the possibility that new T-cell cancers can develop that are unrelated to the B-cell lymphoma or multiple myeloma for which patients were treated with CAR T-cell therapy.
The decision was largely based on data from the FDA Adverse Event Reporting System. However, some researchers have raised concerns that the data may have inherent biases, including reporting bias, Rejeski explained. When assessing the risk of SPMs, it is important to consider confounding factors such as age and duration of follow-up, the type of CAR T-cell therapy received, the patient’s original diagnosis, or other types of treatments the patient received before CAR T-cell therapy, Rejeski said.
“Patients read this in the news and ask providers questions accordingly,” Rejeski said. “We need to understand the potential risks, but at the same time, we need to interpret the data carefully and put it into the proper context for our patients.”
How the study was conducted: Rejeski and colleagues conducted a systematic review and meta-analysis of clinical trials in which adult patients with lymphoma or multiple myeloma received one of the six currently approved CAR T-cell therapies: Idecabtagene Vicleucel (Abecma), Lisocabtagene Maraleucel (Breyanzi), Ciltacabtagene Autoleucel (Carvykti), Tisagenlecleucel (Kymriah), Brexucabtagene Autoleucel (Tecartus), or Axicabtagene Ciloleucel (Yescarta). To meet the inclusion criteria, studies had to provide data on the occurrence of SPMs throughout the entire follow-up period, which ranged from 6.6 months to 65.4 months. The final selection included 18 clinical trials and seven real-world studies, involving a total of 326 SPMs in 5,517 patients.
Results: After a median follow-up of 21.7 months, 5.8% of patients developed an SPM. The researchers found no significant differences in SPM rates between patients with different cancers or between patients who received different CAR T-cell products.
Studies in which patients had received a median of more than three lines of therapy before CAR T-cell treatment showed a significantly higher risk of SPMs than studies in which patients had received fewer than three prior lines of therapy. Similarly, the rate of SPMs was 4.2% in studies with a median follow-up time below 21.7 months and 8.5% in studies with a median follow-up time above that.
Of the 326 SPMs identified in this analysis, hematologic malignancies, including myelodysplastic syndrome and acute myeloid leukemia, accounted for the largest proportion of SPMs at 37%. Five cases were T-cell malignancies, representing a rate of 0.09% in the overall study population. In three of these cases, the malignant T-cells were tested to determine if they contained the CAR transgene (an indicator that the malignancy may have arisen from CAR-edited cells), and one case was positive.
Four of the clinical trials included in the study examined the outcomes of patients treated with CAR T-cell therapy compared to standard therapy. Among a total of 1,253 patients in these studies, the rate of SPMs was 5% in those treated with CAR T and 4.9% in those treated with standard therapy, a difference that was not statistically significant.
