Citations

Purpose We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1. Results Of the 655 patients with melanoma enrolled, 327 had ≥ 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived ≥ 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per both criteria (n = 177). Conclusion Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment.

Incorporation of IL-15 into a bispecific antibody recognizing CD16 and CD33 boosted natural killer cells’ survival and activity against acute myeloid leukemia.

Uveal melanoma is a rare type of melanoma, with only five to seven cases per one million persons diagnosed each year. Patients with metastatic melanoma of uveal origin tend to have lower response rates on traditional therapies. Herein we report our experience with 10 patients with metastatic uveal melanoma (MUM) who received pembrolizumab. Eligible patients were more than or equal to 18 years old, had unresectable MUM, progressed on prior ipilimumab therapy, had good performance status (Eastern Cooperative Oncology Group of 0 or 1), and adequate organ and marrow function. Patients could have central nervous system disease, but needed to be clinically stable. Patients were treated with 2 mg/kg pembrolizumab intravenously over 30 min every 3 weeks until disease progression, unacceptable toxicity, or for up to 2 years. Between April 2014 and October 2014, we treated a total of 10 patients with MUM with pembrolizumab. Median age was 65 years, with 70% being female. As of the data cutoff date of 14 May 2015, median progression-free survival was 18 weeks (range 3.14–49.3 weeks), with four patients still currently receiving therapy. Of eight evaluable patients, there was one complete response, two partial responses, and one patient with stable disease. Four patients had rapidly progressive disease. Toxicities were as expected and were usually grade 1/2 in nature. Although this cohort of patients was small, to our knowledge this is the first such report of outcomes in uveal melanoma patients being treated with anti-PD1 therapy. In the absence of a clinical trial, treatment with pembrolizumab appears to be a viable option for patients with MUM.

Memory T cells promote functional differentiation of naïve T cells and impair the antitumor efficacy of adoptive immunotherapy.

Gut microbiota may modulate the efficacy and/or toxicity of immune checkpoint blockade therapy in cancer.

Radiation therapy for prostate cancer can increase androgen receptor signaling and exacerbate the disease in some patients.

Prolonged inhibition of three HER/EGFR subtypes results in regression of HER2-amplified gastrointestinal carcinomas.

The frequency and prognostic association of molecular markers in colorectal carcinoma differ with anatomic tumor site.

Mismatch repair–deficient tumors have a high rate of somatic mutations, have higher neoantigen formation, and are more sensitive to immune checkpoint blockade.

4-1BB can mitigate CAR endodomain-induced T cell exhaustion and prolong T cell survival.