Chimeric antigen receptor T-cell immunotherapies adverse events reported to FAERS database: focus on cytopenias.

Chimeric antigen receptor (CAR) T-cell therapy presents a promising treatment for hematologic malignancies, displaying high efficacy but not being exempt from toxicity. In this observational study, we assessed adverse events (AEs) reported to the Food and Drug Adverse Event Reporting System (FAERS) including any of the six approved CAR T-cell therapies. A total of 5249 reports mentioning a CAR T-cell as a suspect product were retrieved from the FAERS database, containing a total of 24333 AEs, of which 3236 (13.3%) were cytopenias. The highest number of AEs mentioned by the report was observed for tisagenlecleucel (mean = 6.7), with the lowest for ciltacabtagene (mean = 1.3). Among all reports, hematopoietic leukopenia was the most frequently reported AEs (n = 1386, 5.7%), with hematopoietic erytropenia the least reported (n = 291, 1.2%). Tisagenlecleucel showed a high reporting odds ratio for hematopoietic erythropenia (27.28, 95%CI 14.04-53.00), leukopenia (4.04, 95%CI 3.52-4.64), and thrombocytopenia (4.01, 95%CI 3.19-5.03). Cytopenias represent one of the most frequently reported AEs in FAERS, a CAR T-cell therapy is indicated, with haematopoetic leukopenia being the most common. When comparing different CAR-T cell therapies, the cytopenias' reporting odds ratio was particularly high for tisagenlecleucel, especially in relation to hematopoietic erythropenia.

Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma.

Nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody, showed promising activity in relapsed or refractory (R/R) follicular lymphoma (FL) in a phase 1 study. We conducted a phase 2 trial to further evaluate its efficacy and safety in patients with R/R FL and to explore biomarkers of response. Patients with R/R FL and at least 2 prior lines of therapy, each containing a CD20 antibody or an alkylating agent, were treated with nivolumab 3 mg/kg every 2 weeks. The primary end point was objective response rate (ORR) assessed by an independent radiologic review committee. Biomarker analyses included gene expression profiling and multiplex immunofluorescence studies of pretreatment tumor samples. A total of 92 patients were treated. After a minimum follow-up of 12 months, ORR was 4% (4 of 92 patients). Median progression-free survival (PFS) was 2.2 months (95% confidence interval [CI], 1.9-3.6 months). Median duration of response was 11 months (95% CI, 8-14 months). Exploratory analyses suggested that responders had significantly higher proportion of CD3+ T cells in the tumor microenvironment than nonresponders, but no significant differences in PD-1 or programmed death-ligand 1 expression were observed. High expression of a set of tumor-associated macrophage genes was associated with reduced PFS (hazard ratio, 3.28; 95% CI, 1.76-6.11; P = .001). The safety profile was consistent with previous reports of nivolumab. In conclusion, nivolumab monotherapy was associated with very limited activity in patients with R/R FL. Better understanding of the immune biology of this disease may facilitate the development of effective checkpoint-based strategies. This trial was registered at www.clinicaltrials.gov as #NCT02038946.

Bone marrow evaluation in initial staging of lymphoma: 18F-FDG PET/CT versus bone marrow biopsy.

PURPOSE: The evaluation of bone marrow infiltration (BMI) is of crucial importance in the staging of lymphoma. Although bone marrow biopsy (BMB) is the reference standard for the evaluation of BMI, it has limitations. PET/CT has become an excellent tool in staging of lymphoma, and bone marrow uptake is correlated with the involvement of lymphoma. The aim of this study was to assess the utility of PET/CT and its concordance with BMB in the detection of BMI in patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). PATIENTS AND METHODS: One hundred forty-seven patients with DLBCL (84) and HL (63) were referred for a PET/CT and a BMB (unilateral) at the initial staging. The reference standard was BMB. RESULTS: Bone marrow infiltration was detected by PET/CT in 39 (26%) and by BMB in 21 (14%) cases. There was concordance between PET/CT and BMB in 128 patients (87%) (74 DLBCL, 54 HL), 21 with positive PET/CT and BMB results and 107 with negative PET/CT and BMB results. Discordant results were observed in 19 patients (14%); 18 of them with positive PET/CT and negative standard BMB results (not performed in active sites). The sensitivity, specificity, accuracy, as well as positive and negative predictive values of FDG-PET/CT for the detection of BMI were 95%, 86%, 87%, 54%, and 99%, respectively. CONCLUSIONS: PET/CT detects more bone marrow involvement in DLBCL and HL compared with BMB. Its good concordance with BMB makes it a complementary technique, as it helps select the biopsy site in cases with negative results.