Immune checkpoint inhibitors (ICIs) have improved outcomes for patients with cancer but related hematologic toxicities have been poorly described. Using VigiBase, the World Health Organization's pharmacovigilance database of individual case safety reports of adverse drug reactions, this study aimed to identify such cases of hematologic toxicities.

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BackgroundImmune checkpoint inhibitors (ICIs) have transformed treatment for melanoma, but identifying reliable biomarkers of response and effective modifiable lifestyle factors has been challenging. Obesity has been correlated with improved responses to ICI, although the association of body composition measures (muscle, fat, etc) with outcomes remains unknown.MethodsWe performed body composition analysis using Slice-o-matic software on pretreatment CT scans to quantify skeletal muscle index (SMI=skeletal muscle area/height2), skeletal muscle density (SMD), skeletal muscle gauge (SMG=SMI × SMD), and total adipose tissue index (TATI=subcutaneous adipose tissue area + visceral adipose tissue area/height2) of each patient at the third lumbar vertebrae. We then correlated these measures to response, progression-free survival (PFS), overall survival (OS), and toxicity.ResultsAmong 287 patients treated with ICI, body mass index was not associated with clinical benefit or toxicity. In univariable analyses, patients with sarcopenic obesity had inferior PFS (HR 1.4, p=0.04). On multivariable analyses, high TATI was associated with inferior PFS (HR 1.7, p=0.04), which was particularly strong in women (HR 2.1, p=0.03). Patients with intermediate TATI and high SMG had the best outcomes, whereas those with low SMG/high TATI had inferior PFS and OS (p=0.02 for both PFS and OS).ConclusionsBody composition analysis identified several features that correlated with improved clinical outcomes, although the associations were modest. As with other studies, we identified sex-specific associations that warrant further study.

Background: Anti-programmed cell death protein 1 (PD-1) antibodies (PD1) prolong recurrence-free survival in high-risk resected melanoma; however, approximately 25%e30% of patients recur within 1 year. This study describes the pattern of recurrence, management and outcomes of patients who recur with adjuvant PD1 therapy. Patients and methods: Consecutive patients from 16 centres who recurred having received adjuvant PD1 therapy for resected stage III/IV melanoma were studied. Recurrence characteristics, management and outcomes were examined; patients with mucosal melanoma were analysed separately. Results: Melanoma recurrence occurred in 147 (17%) of w850 patients treated with adjuvant PD1. In those with cutaneous melanoma (n ¼ 136), median time to recurrence was 4.6 months (range 0.3e35.7); 104 (76%) recurred during (ON) adjuvant PD1 after a median 3.2 months and 32 (24%) following (OFF) treatment cessation after a median 12.5 months, including in 21 (15%) who ceased early for toxicity. Fifty-nine (43%) recurred with locoregional disease only and 77 (57%) with distant disease. Of those who recurred locally, 22/59 (37%) subsequently recurred distantly. Eighty-nine (65%) patients received systemic therapy after recurrence. Of those who recurred ON adjuvant PD1, none (0/6) responded to PD1 alone; 8/33 assessable patients (24%) responded to ipilimumab (alone or in combination with PD1) and 18/23 (78%) responded to BRAF/MEK inhibitors. Of those who recurred OFF adjuvant PD1, two out of five (40%) responded to PD1 monotherapy, two out of five (40%) responded to ipilimumab-based therapy and 9/10 (90%) responded to BRAF/MEK inhibitors. Conclusions: Most patients who recur early despite adjuvant PD1 develop distant metastases. In those who recur ON adjuvant PD1, there is minimal activity of further PD1 monotherapy, but ipilimumab (alone or in combination with PD1) and BRAF/MEK inhibitors have clinical utility. Retreatment with PD1 may have activity in select patients who recur OFF PD1.

Purpose We investigated pre- to post-diagnosis weight change and functional limitations in a cohort of breast cancer survivors. Methods A cohort of 1,841 early-stage breast cancer survivors provided information on pre- and post-diagnosis weight and physical function on average 2 years post-diagnosis. The mean number of limitations for each BMI category and each weight change category were compared using the Wilcoxon test. Cross-sectional associations between weight change, from 1 year prior to diagnosis to 2 years post-diagnosis, and functional limitations were determined using logistic regression. Results Women with BMI≥30 kg/m2 had significantly higher physical limitations compared to women with BMI<25 kg/m2 (2.06 vs 0.96 for moderate/severe limitations, 3.92 vs 3.27 for mild limitations, 1.31 vs 0.47 for lower body limitations, and 0.76 vs 0.49 for all other limitations; P<0.0001). Women who reported a large weight gain (≥10 % of pre-diagnosis weight) were more likely to report any limitation (OR=1.79; 95 % confidence interval (CI)=1.23–2.61), a moderate/severe limitation (OR=2.30; 95 % CI=1.75–3.02), and a lower body limitation (OR=2.05; 95 % CI=1.53–2.76) compared to women who maintained weight within 5 % of pre-diagnosis weight. However, associations between weight loss and functional limitations depended on pre-diagnosis BMI and comorbidity status. Among women without comorbidity, large weight loss (≥10 % of pre-diagnosis weight) in normal-weight women was associated with higher risk of functional limitations, whereas among overweight/obese women, large weight loss appeared to be associated with a lower risk of limitations. Among women with comorbidity, moderate weight loss in overweight/obese women was associated with a higher risk of a moderate/severe physical limitation. Conclusions Large weight gain was associated with a higher risk of physical functional limitations, but associations between weight loss and functional limitations may depend on initial BMI and comorbidity status. Implications for Cancer Survivors In this study we found that both weight loss and weight gain among breast cancer survivors were associated with a higher risk of physical functional limitations. Weight maintenance, therefore, may be an important factor in preventing and/or reducing the risk of functional decline in breast cancer survivors.