Margarida de Magalhaes Silverman

The cumulative impact of baseline comorbidities on outcomes of chimeric antigen receptor T-cell (CAR-T) therapy is not well established. Therefore, we developed and validated a Cellular Therapy Comorbidity Index (CT-CI) to predict outcomes following CD19-directed CAR-T therapy for large B-cell lymphoma (LBCL). Patients aged 18 or older receiving commercial CAR-T therapy for LBCL during 2017 to 2020 were selected from the Center for International Blood and Marrow Transplant Research registry. Patients were randomly assigned to training or validation cohorts. Comorbidities given weighted scores comprised the CT-CI, which was then validated for overall survival (OS) prognostication. A total of 1916 patients from 97 medical centers were included, with a median age of 64 years (19-91 years). About 70% of patients had comorbidities, such as cardiac disease (12%); diabetes (14%); hepatic dysfunction (mild, 8%; moderate to severe, 2%); psychiatric disturbance (18%); and pulmonary dysfunction (moderate, 15%; severe, 12%). The CT-CI was calculated, stratified patients in 3 categories, and was associated with increased mortality. Patients with higher CT-CI scores had worse OS (CT-CI 1: hazard ratio [HR], 1.37 [95% confidence interval [CI], 1.16-1.62; P< .001]; CT-CI 2: HR, 1.49 [95% CI, 1.17-1.89; P = .001]; CT-CI ≥ 3: HR, 2.55 [95% CI, 1.90-3.42; P< .001]). Higher CT-CI scores predicted treatment-related mortality and relapse. There was no correlation between the CT-CI score and CAR-T–related toxicities. The novel CT-CI score stratifies the effect of patient comorbidities on survival after CAR-T therapy and can be used for clinical decision-making and treatment selection in high-risk populations. However, comorbidities and fear of increased toxicity should not preclude patients from this effective therapy.

E18515 Background: The outcome of genetically high risk acute myeloid leukemia (AML) patients (pts) remains poor, with a median overall survival (OS) of a few months after the failure of regimens. Long-term survival requires complete remission followed by allogeneic stem cell transplantation (ASCT).Clofarabine, a deoxyadenosine analog, at 20mg/m2 days 1-5, in combination with low-dose cytarabine (LDAC) has reported efficacy and tolerability in older newly diagnosed AML pts (Cancer 2015;121:2375). We have therefore prioritized this combination for relapsed/refractory(R/R) pts. Aims:Determine the efficacy of Clofarabine and low dose cytarabine in R/R AML pts who are eligible for ASCT. Methods: Using Holden Comprehensive Cancer Center database, we performed a retrospective chart review on 16 pts of R/R AML who were treated with Clofarabine and LDAC between January 2014 and Dec 2016. Each patient received Clofarabine 20mg/m²on days 1-5 IV and LDAC on days 1-10 subcutaneous. The primary endpoint was complete remission (CR) or complete remission with incomplete marrow recovery (CRi). Secondary endpoint was median OS. Results: Sixteen pts were analyzed. The median age was 58 years (range 27-78). Nine pts (56%) had AML with high risk characteristics (complex karyotype and/or presence of FLT3-ITD). Nine pts achieved either a CR or CRi. Responses were observed in 7of 9 pts with genetically high-risk features. 2 pts had mutated TP53, and both of them achieved CR. The median OS time was 13.25 months (range 3.6-19.2 months). 4 pts received ASCT after treatment combination. Conclusions: These results suggest that Clofarabine is well-tolerated and effective in the treatment of R/R AML pts, especially those with high-risk genetics. Clofarabine and LDAC could be used as a bridging therapy prior to ASCT for high-risk R/R AML pts. Future clinical trials are warranted to explore additional modifications to this combination in order to optimize therapy for this group of high-risk and heavily treated R/R AML pts.

(2012). Phase II trial of the pan-deacetylase inhibitor panobinostat as a single agent in advanced relapsed/refractory multiple myeloma. Leukemia & Lymphoma: Vol. 53, No. 9, pp. 1820-1823.

We report 4 cases of invasive zygomycosis in hematopoietic stem cell transplant recipients, all occurring after May 2003, when voriconazole began to