Second primary malignancies following CAR T-cell therapy in patients with hematologic malignancies
Elvira Umyarova, Charles Pei, William Pellegrino, Qiuhong Zhao, Nidhi Sharma, Don Benson, Francesca Cottini, Evandro D. Bezerra, Jonathan E. Brammer, Naresh Bumma, Hannah Choe, Nathan Denlinger, Srinivas Devarakonda, Abdullah Khan, Sam Penza, Ashley Rosko, Sumithira Vasu, Sarah Wall, Lapo Alinari, Robert A. Baiocchi, David A. Bond, Beth Christian, Walter Hanel, Kami J. Maddocks, John Reneau, Yazeed Sawalha, Alma Habib, Audrey M. Sigmund, Timothy Voorhees, Marcos de Lima, Narendranath Epperla
Abstract
Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of patients with relapsed/refractory (R/R) hematologic malignancies, including B-cell lymphomas and multiple myeloma (MM). While data pertaining to the efficacy and toxicity associated with CAR-T have been widely reported, there are limited data on long-term complications. We retrospectively analyzed 246 patients treated with CAR-T for R/R B-cell lymphoma (n = 228) and MM (n = 18) at Ohio State University from 2016 to 2022, with a minimum of two years of follow-up. The median age was 66 years, and the median number of prior treatments was four. With a median follow-up of 38 months (range 11-66), 21 patients (8.5%) developed a second primary malignancy (SPM), with non-melanoma skin cancer being the most common (52%), followed by hematologic malignancies (33%) and non-skin solid tumors (14%). Squamous cell carcinoma accounted for 38% of skin cancers, while myelodysplastic syndrome and acute myeloid leukemia were the predominant hematologic malignancies. Solid tumors included bladder, prostate, and breast cancer. The distinct pattern of SPMs suggests potential CAR-T-related risks, warranting vigilant post-treatment surveillance. Further studies are necessary to elucidate underlying mechanism and predictive factors and guide long-term management of SPM risk in CAR-T survivors.