Efficacy of Multiple SARS-CoV-2 Vaccine Doses in Patients with B Cell Hematologic Malignancies Receiving Chimeric Antigen Receptor T Cell Therapy: A Contemporary Cohort Analysis.

The mortality due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) approaches 40% in recipients of chimeric antigen receptor (CAR) T cell therapy (CAR-T). The efficacy of repeated vaccine doses, including bivalent boosters, remains unknown. We examined the efficacy of repeated vaccine doses among CAR-T recipients who received at least 2 or more vaccine doses after T cell infusion. This single-center retrospective study included adults age >18 years receiving CAR-T for relapsed/refractory (R/R) B cell hematologic malignancies targeting CD19, BCMA, or CD19 and CD20 between September 2018 through March 2022 and were alive beyond 2021 to receive incremental SARS-CoV-2 vaccine doses with available seroconversion data. Multivariable analyses were performed using the design-adjusted Cox regression and logistic regression approaches with stratification. In multivariable analysis, seroconversion rates were significantly greater with a total of 4 or more vaccine doses (odds ratio [OR], 8.22; P = .008). CAR-T recipients with other B cell hematologic malignancies had significantly lower seroconversion rates and diminished Ab titers compared to those with R/R multiple myeloma (OR, .07; P = .003). One patient died due to COVID-19 in this vaccinated study cohort, accounting for a COVID-19-attributable mortality rate of 1.7%. The results provide baseline vaccine response data in a contemporary cohort including patients with diverse group of SARS-COV2 variants and support the latest Centers for Disease Control and Prevention guidelines for repeated vaccinations directed against the prevalent variant of concern.

Implementation and evaluation of high-dose methotrexate administration guidelines.

BACKGROUND: High-dose methotrexate is used to treat a variety of malignancies. Methotrexate-associated supportive care and the threshold methotrexate level for the discontinuation of supportive care are not consistent among studies. We evaluated the implementation of high-dose methotrexate administration guidelines, which raised the standard threshold methotrexate level for the discontinuation of supportive care from <0.05 to <0.1 µmol. METHODS: A single-center, observational analysis of patients receiving high-dose methotrexate from 1 January 2015 to 31 May 2017 was conducted. The primary endpoint was time from the start of the methotrexate infusion until the discontinuation of the sodium bicarbonate infusion, before and after guideline implementation. RESULTS: Fifty-two patients met the inclusion criteria, which comprised of a total of 136 individual methotrexate doses and were included in the retrospective analysis. Twenty-four patients were included in the prospective analysis, which comprised a total of 46 individual methotrexate doses. The primary endpoint, time until discontinuation of the sodium bicarbonate infusion, was a median of 97.7 h in the retrospective group versus 73.2 h in the prospective group (p = 0.098). Secondary endpoints also favored patients in the prospective group, including hours of hospitalization, number of methotrexate levels checked, weight gained during admission, and adherence to the guideline. CONCLUSION: Among patients who received high-dose methotrexate, implementation of a guideline using a methotrexate threshold of <0.1 µmol was able to significantly decrease the time to discontinuation of supportive care and subsequently may lead to early hospital discharge given that we did not show a statistical significance.