Michele Waters

Figure S3. Subgroup analysis for ICI-treated patients.

Figure S4. Subgroup analyses for 5-FU-treated patients

Figure S2. Survival following ICI start stratified by SARS-CoV-2 vaccination status from 2017-2022.

Figure S6. Landmarked analysis in the MD Anderson cohort (NSCLC) starting ICI 2020-2022.

Figure S5. Overall survival for patients treated with osimertinib.

Table S1. Characteristics of patients treated with immune checkpoint inhibitors (ICI). Table S2. Characteristics of patients treated with immune checkpoint inhibitors (ICI) stratified by year of ICI start.

Figure S1. Changing event rates over time.

Real-world data suggest that SARS-CoV-2 mRNA vaccines, administered within 100 days of immune checkpoint inhibitor (ICI) treatment (“peri-ICI vaccination”), may improve ICI effectiveness through synergistic immune priming. In an independent real-world cohort and reanalysis of a published cohort, both from tertiary cancer centers in the United States, multiple analyses did not support a treatment-synergy hypothesis. Applying a prior analytic framework, although longer survival with peri-ICI vaccination was observed at the start of the pandemic, this association was not seen in periods when vaccination was broadly available. Longer survival with vaccination in the early pandemic was also not specific to ICI therapies. Progression-free survival during periods of high vaccine uptake was not longer than in prevaccination periods. Together, these findings indicate that the previously reported vaccination survival advantage is largely explained by selection bias, with patients who had more favorable prognoses more likely to receive the SARS-CoV-2 vaccination, particularly in the early pandemic. Significance:The impact of tumor antigen–agnostic vaccination on immunotherapy response is unclear. In a reanalysis of published data and in an independent cohort, after adjustment for multiple confounders, SARS-CoV-2 mRNA vaccination did not improve immunotherapy-related survival in patients with cancer.

Cancer cachexia is a wasting syndrome with outsized impact on morbidity and mortality, yet its drivers and systemic consequences remain poorly defined. In this study, we repurposed longitudinal clinicogenomic data from 52,236 patients with cancer profiled by MSK-IMPACT (2010–2024) at Memorial Sloan Kettering Cancer Center to define episode-resolved trajectories of consensus-defined cachectic weight loss and linked these events to outcomes, serology and tumor genotypes. Cachectic episodes clustered near periods of disease progression and were associated with inferior outcomes in nearly all cancer types. Across diverse malignancies, cachectic weight loss episodes exhibited a consistent serologic signature characterized by lower albumin and hemoglobin and higher levels of liver enzymes. Numerous somatic tumor genotypes, including TP53 mutation across several diseases, were also associated with more frequent onset of cachectic episodes. Motivated by these observations, we developed a multivariate model to predict impending risk of cachectic weight loss in patients with lung, colorectal and prostate cancer, validated in an independent, external cohort from Dana-Farber Cancer Institute (n = 5,785). Routine clinicogenomic data are, therefore, a scalable resource for discovery in cancer cachexia.