Assessment of the safety of nivolumab in people living with HIV with advanced cancer on antiretroviral therapy: the AIDS Malignancy Consortium 095 Study

Abstract

Background: Although immunotherapy has emerged as a therapeutic strategy for many cancers, there are limited studies establishing the safety and efficacy in people living with HIV (PLWH) and cancer.

Methods: PLWH and solid tumors or Kaposi sarcoma (KS) receiving antiretroviral therapy and a suppressed HIV viral load received nivolumab at 3 mg/kg every 2 weeks, in two dose deescalation cohorts stratified by CD4 count (stratum 1: CD4 count > 200/µL and stratum 2: CD4 count 100-199/µL). An expansion cohort of 24 participants with a CD4 count > 200/µL was then enrolled.

Results: A total of 36 PLWH received nivolumab, including 15 with KS and 21 with a variety of other solid tumors. None of the first 12 participants had dose-limiting toxicity in both CD4 strata, and five patients (14%) overall had grade 3 or higher immune related adverse events. Objective partial response occurred in nine PLWH and cancer (25%), including in six of 15 with KS (40%; 95% CI, 16.3-64.7). The median duration of response was 9.0 months overall and 12.5 months in KS. Responses were observed regardless of PDL1 expression. There were no significant changes in CD4 count or HIV viral load.

Conclusions: Nivolumab has a safety profile in PLWH similar to HIV-negative subjects with cancer, and also efficacy in KS. Plasma HIV remained suppressed and CD4 counts remained stable during treatment and antiretroviral therapy, indicating no adverse impact on immune function.

Trial registration: ClinicalTrials.gov Identifier: NCT02408861.

Keywords: CD4 count >100/µL; HIV cancer; immunotherapy; nivolumab.

Figure 1.

CONSORT diagram.

Figure 2.

Swimmer plot demonstrating the duration of therapy in months, best response and time of documented disease progression (months). Unique cases(cases (N=36) are represented as SubjectIDs in y-axis. Axis text in red and blue indicates PD-L1 positive and negative cases, respectively. Cancer types other than KS shown as blue bars, Others included anal cancer (11, 27, 15, and 07), lung cancer (42, 25, 17, 50, and 47), cancers of head & neck (02, 35), colon (54), liver (62), gall bladder (03) and pancreas (61), breast (01), ovary (30), follicular dendritic sarcoma (04), liposarcoma (14), squamous cell carcinoma of skin (06) and inguinal squamous cell cancer (33). Some patients who discontinued therapy before disease. Patients with disease progression were switched to other therapy or not further followed (64, 28, 25, 17, 31, and 26),

Figure 3.

Box and whisker plots of CD4 absolute counts and CD4 CD8 ratio. CD4 absolute counts[a-d] and CD4 CD8 ratio [e-h]: Comparison of the baseline assessment [in blue] to the assessment at four different time points [in yellow; C5D1, C11D1, post-treatment 6 and 16 weeks follow-ups] in same subject. The P-values based on Wilcoxon rank-sum test is shown. Red and blue lines in plots a to d indicates CD4 count levels of 200 and 100 cells/mm3. P-values are based on Wilcoxon test for comparing paired