Second primary malignancies following CAR T-cell therapy in patients with hematologic malignancies.

in Journal of hematology & oncology by Elvira Umyarova, Charles Pei, William Pellegrino, Qiuhong Zhao, Nidhi Sharma, Don Benson, Francesca Cottini, Evandro Bezerra, Jonathan Brammer, Naresh Bumma, Hannah Choe, Nathan Denlinger, Srinivas Devarakonda, Abdullah Khan, Sam Penza, Ashley Rosko, Sumithira Vasu, Sarah Wall, Lapo Alinari, Robert Baiocchi, David A Bond, Beth Christian, Walter Hanel, Kami Maddocks, John Reneau, Yazeed Sawalha, Alma Habib, Audrey Sigmund, Timothy J Voorhees, Marcos de Lima, Narendranath Epperla

TLDR

  • CAR-T therapy for R/R B-cell lymphoma and MM may be associated with long-term risks, including second primary malignancies, particularly non-melanoma skin cancer.

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.

Overview

  • The study investigates long-term complications of chimeric antigen receptor T-cell (CAR-T) therapy in patients with relapsed/refractory (R/R) B-cell lymphoma and multiple myeloma.
  • The retrospective analysis includes 246 patients treated at Ohio State University from 2016 to 2022, with a minimum of two years of follow-up.
  • The primary objective is to identify potential long-term risks and recommend strategies for post-treatment surveillance and long-term management.

Comparative Analysis & Findings

  • Twenty-one patients (8.5%) developed a second primary malignancy (SPM), with non-melanoma skin cancer being the most common (52%).
  • Hematologic malignancies accounted for 33% of SPMs, with squamous cell carcinoma accounting for 38% of skin cancers.
  • The most common solid tumors were bladder, prostate, and breast cancer.

Implications and Future Directions

  • The study suggests potential CAR-T-related risks warranting vigilant post-treatment surveillance.
  • Further studies are necessary to elucidate the underlying mechanism and predictive factors for SPM in CAR-T survivors.
  • Long-term management strategies will require careful consideration of patient risk profiles and individualized care plans.
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