The relationships between absolute lymphocyte counts (ALC), drug- related toxicities, and clinical responses remain unclear in cancer patients treated with PD-1 (programmed cell death 1) inhibitors. We performed a retrospective review of 167 adult solid tumor patients treated with nivolumab or pembrolizumab at a single institution between January 2015 and November 2016. Patients with an ALC >2000 at baseline had an increased risk of irAE (OR 1.996, p<0.05) on multivariate analysis. In a multivariate proportional hazards model, a shorter time to progression was noted in patients who were lymphopenic at baseline (HR 1.45 (p<0.05)) and at three months (HR 2.01 (p<0.05)). Patients with baseline lymphopenia and persistent lymphopenia at month 3 had a shorter time to progression compared to those who had baseline lymphopenia but recovered with ALC > 1000 at 3 months (HR 2.76, p<0.05). Prior radiation therapy was the characteristic most strongly associated with lymphopenia at 3 months (OR 2.24, p<0.001). These data suggest that patients with higher baseline lymphocyte counts have a greater risk for irAE, whereas patients with lymphopenia at baseline and persistent lymphopenia while on therapy have a shorter time to progression on these agents. These associations require further validation in additional patient cohorts.

BackgroundLow absolute lymphocyte count (ALC) has previously been established as a marker of poor prognosis in multiple cancer types. There is growing evidence that ALC may also be associated with response to immunotherapy. This study explores whether response to PD1 inhibitors in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is associated with pretreatment ALC.MethodsThirty-four R/M HNSCC patients who received either nivolumab or pembrolizumab between January 2014 and May 2018 at Johns Hopkins were identified retrospectively. Pretreatment blood counts in patients with and without clinical benefit from PD1 inhibitors were compared. Time-to-progression analyses were performed by dichotomizing the study cohort with the threshold of ALC 600 cells/μl, which is approximately 1.5 standard deviations away from treatment-naïve baseline mean.ResultsPatients with lower ALC appeared to have significantly less clinical benefit from anti-PD1 therapy. Those patients with pretreatment ALC < 600 cells/μl also had shorter PFS than patients with pretreatment ALC ≥ 600 cells/μl (median PFS 60 days vs. 141 days, p < 0.05). These results were consistent with multivariate proportional hazards analyses demonstrating significant association with progression. These observations were further supported by an expansion cohort analysis incorporating additional fourteen R/M HNSCC patients who received other checkpoint immunotherapy regimens at our institution.ConclusionsThis study for the first time demonstrates that pretreatment ALC is significantly associated with response to PD1 inhibitors in R/M HNSCC patients.Electronic supplementary materialThe online version of this article (10.1186/s40425-018-0395-x) contains supplementary material, which is available to authorized users.

(1972). Brit. J. industr. Med., 29,[225][226][227][228]. Chronic inorganic mercury poisoning treated with N-acetyl-D-penicillamine. The case history is presented of a man intoxicated by mercury during his employment as a filler of thermometers. The mean daily urinary excretion of mercury was 661 ,ug for five estimations before treatment. The mean excretion was 875 ,ug for the first 10 days after beginning N-acetyl-D-p_nicillamine, 600 mg/day. This difference is not significant (P < 0 1). The literature of the treatment of mercury poisoning is briefly reviewed.