Key PointsQuestionDid cancer mortality during the COVID-19 pandemic deviate from expected pre-pandemic trends at the site-specific level?FindingsIn this population-based study of more than 60 million cancer deaths in the United States, overall cancer mortality remained aligned with pre-pandemic declines. However, site-specific counterfactual modeling revealed heterogeneous divergence, including excess mortality for Hodgkin lymphoma (mean +9.5%) and prostate cancer (mean +7.9%), and below-expected mortality for liver cancer (mean −15.5%), along with increases in deaths attributed to ill-defined cancer categories (mean +15.2%).MeaningThese findings suggest that pandemic-related health system disruption produced uneven, disease-specific mortality effects that are not captured by aggregate cancer mortality trends, highlighting the importance of site-level monitoring to detect delayed consequences of large-scale healthcare disruption.

Background: Idecabtagene vicleucel (ide-cel) has demonstrated substantial activity in relapsed/refractory multiple myeloma (RRMM), but outcomes in real-world patients remain heterogeneous. Extramedullary disease (EMD) is an adverse phenotype, and prolonged cytopenias may complicate post-CAR-T recovery. We synthesized real-world standard-of-care ide-cel evidence to characterize EMD-associated efficacy outcomes and prolonged hematotoxicity. Methods: We performed a focused evidence synthesis of real-world ide-cel studies reporting EMD-stratified outcomes, cytopenias, hematopoietic interventions, or safety in RRMM. Data were extracted into a structured workbook. Because several US datasets were derived from potentially overlapping registry or consortium populations, primary EMD prevalence and progression-free survival (PFS) synthesis was restricted to non-overlapping EMD-stratified cohorts. Progression-free survival (PFS) was analyzed in parallel across contributing cohorts rather than pooled mathematically. Cytopenia outcomes were summarized descriptively at day 30/month 1 and day 90/month 3. Results: Five real-world studies were included. Across two non-overlapping ide-cel-only EMD-stratified cohorts, 111 of 510 infused patients had reported EMD, corresponding to a combined study-reported prevalence of 21.8% (17.0% in the French registry and 23.9% in the US cohort). Median PFS was shorter with EMD in both contributing cohorts: 6.21 versus 14.82 months in FENIX/DESCAR-T and 5.3 versus 11.1 months in the US EMD-focused cohort. Across both independent cohorts, presence of extramedullary disease was consistently associated with significantly inferior progression-free survival: median PFS was 6.21 months (95% CI: 4.01–NR) versus 14.82 months (95% CI: 11.30–18.37) in the French FENIX/DESCAR-T cohort (adjusted HR 3.15, 95% CI: 1.82–5.47; p < 0.0001), and 5.30 months (95% CI: 4.10–6.90) versus 11.10 months (95% CI: 9.20–12.60) in the US cohort (adjusted HR 1.50, 95% CI: 1.10–2.20; p = 0.02). In the US EMD-focused cohort, day-90 ORR was 52% with EMD versus 82% without EMD. EMD independently predicted inferior PFS in both adjusted analyses. A multicenter cohort evaluating both ide-cel and ciltacabtagene autoleucel (cilta-cel) contributed supportive evidence, with ide-cel-treated EMD patients achieving a best overall response rate (ORR) of 61% (≥PR per IMWG criteria). In the cytopenia-focused cohort, grade ≥ 3 cytopenia was present in 64.7% at day 30 and 40.4% at day 90. Grade ≥ 3 thrombocytopenia was present at day 90/month 3 in 20.8–27.7% across ide-cel-only hematotoxicity studies. Conclusions: Real-world ide-cel data identify EMD as a high-risk phenotype associated with inferior response durability and approximately halved median PFS. Prolonged grade ≥ 3 cytopenias are common after standard-of-care ide-cel, particularly thrombocytopenia and neutropenia. These findings support pre-infusion risk stratification incorporating true EMD status, marrow disease burden, and hematopoietic reserve.