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BACKGROUND The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern. METHODS We reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR T cells, and the normal hematopoietic cells in the patient. RESULTS A total of 724 patients who had received T-cell therapies at our center were in- cluded in the study. A lethal T-cell lymphoma was identified in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma, and both lymphomas were deeply profiled. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein-Barr virus and were associated with DNMT3A and TET2 mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques. CONCLUSIONS Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.). [ABSTRACT FROM AUTHOR]

Indolent CD4+ cytotoxic chimeric antigen receptor (CAR) T-cell lymphoma involving the small intestine was diagnosed in a patient who had previously received ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy for treatment of myeloma. Targeted messenger RNA sequencing revealed the presence of CAR gene product in tumor cells. Whole-genome sequencing of samples of tumor and peripheral blood identified a single lentiviral insertion site within the second intron of the SSU72 gene. In addition, numerous genetic alterations that may have contributed to malignant transformation were identified in the tumor sample. (Funded by MedStar Georgetown University Hospital. [ABSTRACT FROM AUTHOR]

BACKGROUND Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear. METHODS We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored. RESULTS After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease--negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100). CONCLUSIONS Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.) [ABSTRACT FROM AUTHOR]

The article focuses on the contrasting outcomes of CAR T-cell therapy in patients with systemic lupus erythematosus (SLE) and systemic sclerosis, highlighting prompt clinical and serologic remission in SLE patients but less complete remission in systemic sclerosis patients, suggesting that CAR T-cell therapy efficacy may vary based on autoimmune condition and emphasizing the need for tailored approaches rather than a universal solution.

The article focuses on secondary cancers that have arisen after Chimeric Antigen Receptor (CAR) T-cell therapy, highlighting the risks associated with this innovative treatment for hematologic cancers. Topics discussed include the incidence of T-cell cancers following CAR T-cell therapy, mechanisms of oncogenesis related to retroviral vectors, and recommendations for monitoring and reporting adverse events to regulatory agencies.

The article focuses on the contrasting outcomes of CAR T-cell therapy in patients with systemic lupus erythematosus (SLE) and systemic sclerosis, highlighting prompt clinical and serologic remission in SLE patients but less complete remission in systemic sclerosis patients, suggesting that CAR T-cell therapy efficacy may vary based on autoimmune condition and emphasizing the need for tailored approaches rather than a universal solution.

The article focuses on the contrasting outcomes of CAR T-cell therapy in patients with systemic lupus erythematosus (SLE) and systemic sclerosis, highlighting prompt clinical and serologic remission in SLE patients but less complete remission in systemic sclerosis patients, suggesting that CAR T-cell therapy efficacy may vary based on autoimmune condition and emphasizing the need for tailored approaches rather than a universal solution.