Optimization of older adults by a geriatric assessment-guided multidisciplinary clinic before CAR T-cell therapy.

ABSTRACT: The optimal means of assessing candidacy of older adults (≥65 years) for chimeric antigen receptor T-cell (CAR-T) therapy are unknown. We explored the role of a geriatric assessment (GA)-guided multidisciplinary clinic (GA-MDC) in selecting and optimizing older adults for CAR-T. Sixty-one patients were evaluated in a GA-MDC (median age, 73 years; range, 58-83). A nonbinding recommendation ("proceed" or "decline") regarding suitability for CAR-T was provided for each patient based on GA results. Fifty-three patients ultimately received CAR-T (proceed, n = 47; decline, n = 6). Among patients who received B-cell maturation antigen (BCMA)-directed (n = 11) and CD19-directed CAR-T (n = 42), the median overall survival (OS) was 14.2 months and 16.6 months, respectively. GA uncovered high rates of geriatric impairment among patients proceeding to CAR-T therapy, with fewer impairments in those recommended "proceed." Patients recommended "proceed" had shorter median length of stay (17 vs 31 days; P = .05) and lower rates of intensive care unit admission (6% vs 50%; P = .01) than those recommended "decline." In patients receiving CD19- and BCMA-directed CAR-T therapy, a "proceed" recommendation was associated with superior OS compared with "decline" (median, 16.6 vs 11.4 months [P = .02]; and median, 16.4 vs 4.2 months [P = .03], respectively). When controlling for Karnofsky performance status, C-reactive protein, and lactate dehydrogenase at time of lymphodepletion, the GA-MDC treatment recommendation remained prognostic for OS (hazard ratio, 3.26; P = .04). Patients optimized via the GA-MDC without serious vulnerabilities achieved promising outcomes, whereas patients with high vulnerability experienced high toxicity and poor outcomes after CAR-T therapy.

Treatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era.

ABSTRACT: Progression of myeloproliferative neoplasms (MPNs) to accelerated or blast phase is associated with poor survival outcomes. Since 2017 there have been several therapies approved for use in acute myeloid leukemia (AML); these therapies have been incorporated into the management of accelerated/blast-phase MPNs (MPN-AP/BP). We performed a multicenter analysis to investigate outcomes of patients diagnosed with MPN-AP/BP in 2017 or later. In total, 202 patients were identified; median overall survival (OS) was 0.86 years. We also analyzed patients based on first-line treatment; the 3 most common approaches were intensive chemotherapy (n = 65), DNA methyltransferase inhibitor (DNMTi)-based regimens (n = 65), and DNMTi + venetoclax-based regimens (n = 54). Median OS was not significantly different by treatment type. In addition, we evaluated response by 2017 European LeukemiaNet AML criteria and 2012 MPN-BP criteria in an effort to understand the association of response with survival outcomes. We also analyzed outcomes in 65 patients that received allogeneic hematopoietic stem cell transplant (allo-HSCT); median OS was 2.30 years from time of allo-HSCT. Our study demonstrates that survival among patients with MPN-AP/BP is limited in the absence of allo-HSCT even in the current era of therapeutics and underscores the urgent need for new agents and approaches.

First-Line Respiratory Support for Children With Hematologic Malignancy and Acute Respiratory Failure.

OBJECTIVES: To characterize trends in noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) use over time in children with hematologic malignancy admitted to the PICU with acute respiratory failure (ARF), and to identify risk factors associated with NIV failure requiring transition to IMV. DESIGN: Retrospective cohort analysis using the Virtual Pediatric Systems (VPS, LLC) between January 1, 2010 and December 31, 2019. SETTING: One hundred thirteen North American PICUs participating in VPS. PATIENTS: Two thousand four hundred eighty children 0-21 years old with hematologic malignancy admitted to participating PICUs for ARF requiring respiratory support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 3013 total encounters, of which 868 (28.8%) received first-line NIV alone (NIV only), 1544 (51.2%) received first-line IMV (IMV only), and 601 (19.9%) required IMV after a failed NIV trial (NIV failure). From 2010 to 2019, the NIV only group increased from 9.6% to 43.1% and the IMV only group decreased from 80.1% to 34.2% (p < 0.001). The NIV failure group had the highest mortality compared with NIV only and IMV only (36.6% vs. 8.1%, vs. 30.5%, p < 0.001). However, risk-of-mortality (ROM) was highest in the IMV only group compared with NIV only and NIV failure (median Pediatric Risk of Mortality III ROM 8.1% vs. 2.8% vs. 5.5%, p < 0.001). NIV failure patients also had the longest median PICU length of stay compared with the other two study groups (15.2 d vs. 6.1 and 9.0 d, p < 0.001). Higher age was associated with significantly decreased odds of NIV failure, and diagnosis of non-Hodgkin lymphoma was associated with significantly increased odds of NIV failure compared with acute lymphoid leukemia. CONCLUSIONS: For children with hematologic malignancy admitted to the PICU with ARF, NIV has replaced IMV as the most common initial therapy. NIV failure rate remains high with high-observed mortality despite lower PICU admission ROM.