Risk of graft-versus-host disease with rituximab-containing conditioning regimens in allogeneic hematopoietic stem cell transplant.

Graft-versus-host disease represents a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant patients. There is growing evidence that B lymphocytes may play a role in the pathogenesis of acute graft-versus-host disease. The purpose of this retrospective cohort study was to evaluate the efficacy of rituximab-containing conditioning regimens in decreasing graft-versus-host disease in allogeneic hematopoietic stem cell transplant patients who received standardized tacrolimus-based graft-versus-host disease prophylaxis regimens. Patients were divided into two cohorts, based on the presence (RTX, n = 54) or absence (No-RTX, n = 105) of rituximab in the conditioning regimen and were matched 1:2 for major graft-versus-host disease risk factors. The incidence of grade II-IV acute graft-versus-host disease was not different between the two groups (37% vs. 26%, p = 0.147). When restricting the analysis to recipients of peripheral blood hematopoietic stem cell transplants, the RTX group had a higher incidence of grade II-IV acute graft-versus-host disease, relapse, or death prior to day 100 (55% vs. 36%, p = 0.037). The median time to the onset of acute graft-versus-host disease was no different between the RTX and No-RTX groups (67 vs. 74 days, respectively, p = 0.141). Inhibition of antigen presentation by B cells with rituximab-based conditioning regimens does not appear to reduce the incidence of acute graft-versus-host disease in allogeneic hematopoietic stem cell transplant recipients.

Comparing 2-day vs 3-day flu-CY lymphodepleting regimens for CD19 CAR T-cell therapy in patients with non-hodgkin's lymphoma.

Introduction: Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency. Methods: We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity. Results: From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026). Discussion: As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.

Implementation of the Quality Oncology Practice Initiative at a university comprehensive cancer center.

PURPOSE: The Quality Oncology Practice Initiative (QOPI) is a voluntary program developed by the American Society of Clinical Oncology (ASCO) to aid oncology practices in quality self-assessment. Few academic cancer centers have been QOPI participants. METHODS: We implemented the QOPI process at the University of Michigan Comprehensive Cancer Center, a large, hospital-based academic cancer center, and report our experience with five rounds of data collection. Patient medical records were selected using QOPI-specified procedures and abstracted locally; results were entered into an ASCO-maintained database and analyzed. RESULTS: Abstractors who were not directly involved with patient care required an average of 62.3 minutes per medical record (4.7 minutes per data element) to abstract data. We found that compliance with quality measures was uniformly high when measures were structured into our electronic medical record. Results from other measures, including those measuring chemotherapy administration in the last 2 weeks of life, were initially markedly different from those reported by other QOPI participants. Our practice changed toward the QOPI national practice norm after a presentation of the results at a faculty research conference. We found that other measures were consistently greater than 90%, including disease-specific diagnosis and treatment measures. CONCLUSION: Measuring and showing performance data to physicians was sufficient to change some aspects of physician behavior. Improvement in other measures requires structural practice changes. QOPI, an oncologist-developed system, can be adapted for use in practice improvement at an academic medical center.