Immune checkpoint blockade has emerged as a therapeutic strategy for cancers. The objective of this phase I study was to evaluate the safety/tolerability and describe immune-mediated effects of nivo in patients (pts) with HIV-associated ST.
Pts received nivo at 3 mg/kg q 2 wk, in two dose de-escalation cohorts stratified by CD4 count (Stratum 1: CD4 counts
A total of 37 pts were treated with nivo (n=4, 9, 24 for strata 1/2 and expansion cohorts). Histologies included Kaposi Sarcoma [KS](n=15), anal cancer [ca](n=5), lung ca (n=4) and other ST (n=13). No pts experienced dose-limiting toxicities (evaluable n=3 [stratum 1] and n=6 [stratum 2]). Treatment-related adverse events (AEs) were experienced by 14 (38%) pts. The most common treatment-related AEs were fatigue (n=5) and maculo-papular rash (n=4); of which, grade 3/4 severity was experienced by 2 pts each. Objective response rate (RR) by modified WHO criteria was 24% (9/37); with partial response (PR) in pts with KS (n=5), anal ca (n=1), colon ca (n=1), adenocarcinoma of the gall bladder (n=1), and squamous cell ca (n=1). There were no significant changes detected in HIV viral load (VL) during the study, which was undetectable for 97% of participants at baseline. Baseline median absolute CD4 was 315 (IQR, 225-434), and there was a trend for a reduction at 6-week (wk) post-treatment follow-up [f/u] (median difference: -35 (IQR, -83 to 37), p=0.072). Median CD4/CD8 ratio at baseline was 0.41 (IQR, 0.33-0.75) and increased by a median of 0.10 (IQR, -0.05 to 0.14, p=0.060) and 0.08 (IQR, 0 to 0.18, p=0.021) at 6- and 16 wk post-treatment f/u.
Nivo has acceptable safety in HIV patients with ST. Plasma viremia remained suppressed during the study suggesting no viral reactivation, and CD4/CD8 count ratio was increased at 16 wk post-treatment. A RR of 24% was observed in tumors known to be responsive to ICB. Thus, it is appropriate for HIV+ pts with ST treated with ART and a CD4+ T-cell count of greater than 100 cells/μL and undetectable VL to receive nivo in clinical trials and FDA-approved indications.
AMC (AIDS Malignancy Consortium).
NCI Grant #UM1CA121947.
L. Rajdev: Honoraria (self), Travel/Accommodation/Expenses: Bayer Pharmaceuticals. R. Baiocchi: Honoraria (self), Advisory/Consultancy, Leadership role, Research grant/Funding (self): Prelude Tx, Viracta. C-C.J. Wang, M.S. Lee: Research grant/Funding (institution): Bristol-Myers Squibb. All other authors have declared no conflicts of interest.