Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium.

PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. CONCLUSION: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Response to selpercatinib in a patient with RET fusion-positive pulmonary large-cell neuroendocrine carcinoma: A case report.

Large-cell neuroendocrine carcinoma (LCNEC) is a rare subtype of non-small-cell lung cancer associated with a poor prognosis. LCNEC is genetically heterogeneous, and studies have revealed distinct molecular subtypes of LCNEC, which may have therapeutic implications. Herein, we present a case of a patient with stage IV LCNEC harboring a KIF5B-RET fusion whose disease responded to the selective RET inhibitor selpercatinib both extra- and intra-cranially, highlighting the importance of comprehensive molecular testing in LCNEC for selection of optimal treatment.

A Rare Case of Autoimmune Demyelinating Polyneuropathy and Hydrocephalus Secondary to Pembrolizumab.

Pembrolizumab is a humanized monoclonal antibody that targets the programmed cell death 1 protein (PD-1) receptor and blocks the inhibitory checkpoint interaction between PD-1 and its ligands. This interaction leads to the upregulation of effector T-cells and downregulating regulatory T-cell production. Although this mechanism is essential for the management of cancer, it may lead to decreased self-tolerance with an autoimmune reaction toward healthy functioning tissue. One of the less commonly reported and less understood immune-related adverse events includes neuromuscular complications. We present a rare case of autoimmune demyelinating polyneuropathy and hydrocephalus secondary to pembrolizumab use for cutaneous squamous cell carcinoma of the cheek.