Effect of CD4+ T cell count on treatment-emergent adverse events among patients with and without HIV receiving immunotherapy for advanced cancer

Abstract

BackgroundThe Food and Drug Administration recommends that people living with HIV (PWH) with a CD4+ T cell count (CD4) ≥350 cells/µL may be eligible for any cancer clinical trial, but there is reluctance to enter patients with lower CD4 counts into cancer studies, including immune checkpoint inhibitor (ICI) studies. Patients with relapsed or refractory cancers may have low CD4 due to prior cancer therapies, irrespective of HIV status. It is unclear how baseline CD4 prior to ICI impacts the proportion of treatment-emergent adverse events (TEAE) and whether it differs by HIV status in ICI treated patients.MethodsWe conducted a pilot retrospective cohort study of participants eligible for ICI for advanced cancers from three phase 1/2 trials in the USA and Spain. We determined whether baseline CD4 counts differed by HIV status and whether the effect of CD4 counts on incidence of TEAE was modified by HIV status using a multivariable logistic regression model.ResultsOf 122 participants, 66 (54%) were PWH who received either pembrolizumab or durvalumab and 56 (46%) were HIV-negative who received bintrafusp alfa. Median CD4 at baseline was 320 cells/µL (IQR 210–495) among PWH and 356 cells/µL (IQR 260–470) among HIV-negative participants (p=0.5). Grade 3 or worse TEAE were recorded among 7/66 (11%) PWH compared with 7/56 (13%) among HIV-negative participants. When adjusted for prior therapies, age, sex, and race, the effect of baseline CD4 on incidence of TEAE was not modified by HIV status for any TEAE (interaction term p=0.7), or any grade ≥3 TEAE (interaction term p=0.1).ConclusionsThere was no significant difference in baseline CD4 or the proportions of any TEAE and grade ≥3 TEAE by HIV status. CD4 count thresholds for cancer clinical trials should be carefully reviewed to avoid unnecessarily excluding patients with HIV and cancer.

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

“…19,20 We showed that the 24-month incidence rate of irAEs of any grade in this group is comparable with PWH with CD41 T-cell counts >200 cells/mL. Similar findings have been reported by Odeny et al, 17 where the effect of baseline CD41 T-cell counts on the incidence of treatment-emergent adverse events was not modified by HIV status. These data further endorse the need to abrogate arbitrary CD4 cutoffs when using ICIs in the appropriate setting for the treatment of PWH and subsequently reduce barriers to ICI access on the basis of their favorable benefit-to-risk profiles.…”

“…11 However, recent clinical trials and retrospective studies that included PWH demonstrated that ICIs were active and safe for PWH, although these observations were hampered by small sample sizes and heterogeneous tumor types. [11][12][13][14][15][16][17][18][19][20][21] Given the potential benefit of ICIs in PWH and cancer, 22 larger real-world cohorts are needed to address the existing knowledge gaps, guide clinical decision making, and increase therapeutic opportunities for PWH. Herein, we implement a grassroots effort and assemble a real-world international cohort of PWH who received ICIs for advanced cancers.…”

Cancer Treatment Decision-Making for People Living With HIV: Physician-Reported Barriers, Facilitators, and Recommendations

“…Furthermore, medical oncologists reported using CD4 counts to determine candidacy for systemic therapy; this may inadvertently exclude PLWHC from receiving novel cancer treatments (eg, immunotherapy) or enrolling in clinical trials. 16 Efforts to address these gaps with design of inclusive trials and dissemination of clinical management guidelines are underway. 17 Several oncologists expressed views that appeared to conflate patient risks with stereotypes of PLWH.…”

Treating Cancer in People With HIV

“…[19][20][21] Comparisons between people with and without HIV receiving anti-PD-(L)1 therapies with CD4 1 T-cell counts <350 cells/mL have not shown significant differences in rates of immune-mediated adverse events. 22 There are also data to support the safety of anti-PD-(L)1 agents with chronic infections frequently seen in PWH. For example, there are data for the safe use of these agents in people with HBV receiving concurrent suppressive HBV therapy as well as in people with untreated HCV.…”