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Background Hematopoietic cell transplant (HCT) or chimeric antigen receptor (CAR) T-cell therapy recipients have high morbidity from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are limited data on outcomes from SARS-CoV-2 infection shortly before cellular therapy and uncertainty whether to delay therapy. Methods We conducted a retrospective cohort study of patients with SARS-CoV-2 infection within 90 days before HCT or CAR-T-cell therapy between January 2020 and November 2022. We characterized the kinetics of SARS-CoV-2 detection, clinical outcomes following cellular therapy, and impact on delays in cellular therapy. Results We identified 37 patients (n = 15 allogeneic HCT, n = 11 autologous HCT, n = 11 CAR-T-cell therapy) with SARS-CoV-2 infections within 90 days of cellular therapy. Most infections (73%) occurred between March and November 2022, when Omicron strains were prevalent. Most patients had asymptomatic (27%) or mild (68%) coronavirus disease 2019 (COVID-19). SARS-CoV-2 positivity lasted a median of 20.0 days (interquartile range, 12.5–26.25 days). The median time from first positive SARS-CoV-2 test to cellular therapy was 45 days (interquartile range, 37.75–70 days); 1 patient tested positive on the day of infusion. After cellular therapy, no patients had recrudescent SARS-CoV-2 infection or COVID-19–related complications. Cellular therapy delays related to SARS-CoV-2 infection occurred in 70% of patients for a median of 37 days. Delays were more common after allogeneic (73%) and autologous (91%) HCT compared to CAR-T-cell therapy (45%). Conclusions Patients with asymptomatic or mild COVID-19 may not require prolonged delays in cellular therapy in the context of contemporary circulating variants and availability of antiviral therapies. [ABSTRACT FROM AUTHOR]

Background The epidemiology of cytomegalovirus (CMV) after chimeric antigen receptor–modified T-cell immunotherapy (CARTx) is poorly understood owing to a lack of routine surveillance. Methods We prospectively enrolled 72 adult CMV-seropositive CD19-, CD20-, or BCMA-targeted CARTx recipients and tested plasma samples for CMV before and weekly up to 12 weeks after CARTx. We assessed CMV-specific cell-mediated immunity (CMV-CMI) before and 2 and 4 weeks after CARTx, using an interferon γ release assay to quantify T-cell responses to IE-1 and pp65. We tested pre-CARTx samples to calculate a risk score for cytopenias and infection (CAR-HEMATOTOX). We used Cox regression to evaluate CMV risk factors and evaluated the predictive performance of CMV-CMI for CMV reactivation in receiver operator characteristic curves. Results CMV was detected in 1 patient (1.4%) before and in 18 (25%) after CARTx, for a cumulative incidence of 27% (95% confidence interval, 16.8–38.2). The median CMV viral load (interquartile range) was 127 (interquartile range, 61–276) IU/mL, with no end-organ disease observed; 5 patients received preemptive therapy based on clinical results. CMV-CMI values reached a nadir 2 weeks after infusion and recovered to baseline levels by week 4. In adjusted models, BCMA-CARTx (vs CD19/CD20) and corticosteroid use for >3 days were significantly associated with CMV reactivation, and possible associations were detected for lower week 2 CMV-CMI and more prior antitumor regimens. The cumulative incidence of CMV reactivation almost doubled when stratified by BCMA-CARTx target and use of corticosteroids for >3 days (46% and 49%, respectively). Conclusions CMV testing could be considered between 2 and 6 weeks in high-risk CARTx recipients. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T‐cell (CAR T) therapy has shown promising efficacy in relapsed and refractory diffuse large B cell lymphoma (DLBCL). While most patients undergo CAR T infusion with active disease, the impact of some clinical variables, such as responsiveness to the pre‐CAR T chemotherapy on the response to CAR T, is unknown. In this single‐institution study, we studied the impact of several pre‐CAR T variables on the post‐CAR outcomes. Sixty patients underwent apheresis for axicabtagene‐ciloleucel (axi‐cel) and 42 of them (70.0%) had primary refractory disease. Bridging therapy between apheresis and lymphodepletion was given in 34 patients (56.7%). After axi‐cel, the overall response rate was 63.3%. Responsiveness to the immediate pre‐CAR T therapy did not show a significant association with response to axi‐cel, progression‐free (PFS) or overall (OS) survival. Multivariable analysis determined that bulky disease before lymphodepletion was independently associated with inferior outcomes, and patients that presented with high‐burden disease unresponsive to immediate pre‐CAR T therapy had a dismal outcome. This data supports proceeding with treatment in CAR T candidates regardless of their response to immediate pre‐CAR T therapy. Interim therapeutic interventions should be considered in patients who have known risk factors for poor outcomes (bulky disease, high LDH). [ABSTRACT FROM AUTHOR]

Cytopenias are important but less studied adverse events following chimeric antigen receptor-engineered T cell (CAR-T) therapy. In our analysis of patients with large cell lymphoma who received axicabtagene ciloleucel (axi-cel), we sought to determine the rate and risk factors of clinically significant short term cytopenias defined as grade ≥3 neutropenia, anemia, or thrombocytopenia, or treatment with growth factors or blood product transfusions between days 20–30 after axi-cel. Fifty-three pts received axi-cel during the study period and severe cytopenias were observed in 32 (60%) pts. Significant cytopenias were more common in non-responders (stable or progressive disease) vs. responders (partial or complete response) (100% vs. 70%; p =.01). In the multivariable model, platelet transfusion within a month before leukapheresis, number of red blood cell and platelet transfusions between leukapheresis to lymphodepletion, pre-lymphodepletion absolute neurophil count, pre-lymphodepletion lactate dehydrogenase, and number of dexamethasone treatments after CAR-T were significantly associated with severe cytopenias after axi-cel. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Relapse and graft‐vs‐host disease (GVHD) are still the main complications after allogeneic hematopoietic stem cell transplantation, especially in the setting of reduced intensity regimen (RIC) and unrelated donor. We compared here anti‐thymocyte globulin (ATG) or alemtuzumab as GVHD prophylaxis in patients with myeloid disease transplanted after RIC and from an unrelated donor. Method: ATG and alemtuzumab patients have been matched by age, gender, HLA matching, comorbidities and cytogenetics risk (119 patients in each group). Results: After matching, we found that ATG decreased the risk of relapse (HR: 0.55, P = .0049) and improved relapse‐free survival (RFS, HR: 0.70, P = .042). The improved RFS with ATG was more pronounced in CMV‐positive patients but was not influenced by disease risk. Regarding overall survival, GVHD‐free relapse‐free survival and transplant‐related mortality, the risk was similar using ATG or alemtuzumab. Conclusion: Even if GVHD risk is lowered by alemtuzumab use, it does not translate in better outcome due to higher risk of relapse. [ABSTRACT FROM AUTHOR]