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Pembrolizumab demonstrates acceptable safety among patients with cancer and HIV
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CHICAGO — Pembrolizumab exhibited an acceptable safety profile among patients with cancer and HIV who had more than 100 CD4 cells/µL and received antiretroviral therapy, according to results of a phase 1 trial presented at ASCO Annual Meeting.
“We don’t look at CD4 counts that commonly in [patients with] cancer, but many [patients with] cancer who receive cancer therapies also have low CD4 counts,” Thomas S. Uldrick, MD, MS, deputy head of global oncology, associate member of the vaccine and infectious disease division and associate member of the clinical research division at Fred Hutchinson Cancer Research Center, said in an interview with HemOnc Today. “Because it’s difficult to differentiate what is due to a cancer therapy and what is due to HIV, we decided to come up with criteria around lack of opportunistic infections, so we could look across a broad range of CD4 counts.”
In the multicenter, phase 1 trial, Uldrick and colleagues evaluated 30 patients (median age, 57 years; range, 39-77; 28 men; 60% white; 30% black; 10% Hispanic) with advanced cancer, an ECOG score of 1 or less, 100 or more CD4 cells/L (median, 285 cells/L; range, 132-966), 4 or more weeks of antiretroviral therapy, and an HIV viral load of less than 200 copies/mL.
Patients had Kaposi sarcoma (n = 6), non-Hodgkin lymphoma (n =5) and non-AIDS defining cancers (n =19), the most common of which were anal (n = 6) and squamous cell skin cancer (n = 3). Nineteen patients had previously undergone radiation, and the number of median prior systemic therapies was two (range, 0-8).
The researchers assigned participants to the following cohorts based on CD4 counts: C1 (100-199 cells/L; n = 6); C2 (200-350 cells/L; n = 12) and C3 (more than 350 cells/L; n = 12). Participants received 200 mg IV pembrolizumab (Keytruda, Merck) every 3 weeks for up to 35 doses. The researchers used Common Terminology Criteria for Adverse Events to evaluate grade 2 or higher immune-related adverse events. They estimated clinical benefit based on tumor shrinkage or stable disease for at least 24 weeks.
Upon completion of patient accrual for C2 and C3 and administration of at least two cycles of treatment to all participants, the researchers locked data for safety analysis and publication. They continued accrual for six C1 participants and a new phase 1b Kaposi sarcoma cohort.
Results showed pembrolizumab appeared safe over 183 treatment cycles.
Adverse events that emerged after treatment and may have been linked to pembrolizumab were primarily grade 1 and grade 2, with 20% of patients experiencing grade 3 adverse events. Immune-related events of clinical interest included hypothyroidism (n = 6); elevated aspartate aminotransferase/alanine aminotransferase (n = 1); pneumonitis (n = 3); rash (n = 2) and musculoskeletal adverse events (n = 1).
One patient in the Kaposi sarcoma group developed and died of Kaposi sarcoma herpesvirus-related multicentric Castleman disease.
The researchers observed HIV control and increases in CD4 counts among the cohorts.
Uldrick said future studies will further evaluate pembrolizumab among patients with non-Hodgkin lymphoma achieved partial response and two patients with Kaposi sarcoma experienced stable disease for 24 weeks or more. Thirteen patients had stable disease for less than 24 weeks, 10 patients had progressive disease and two could not be assessed.
Uldrick said future studies will further evaluate pembrolizumab among patients with HIV and specifically assess its effect among patients with Kaposi sarcoma.
“The next step, if one were to think about drug development for specific indications, would be to evaluate efficacy. The original hypothesis we had is that the drug may work as well or better in HIV patients with cancers for which we know the drug works, like lung cancer and classic Hodgkin lymphoma,” Uldrick told HemOnc Today. “Trying to determine efficacy in at least these diseases is of interest. We’re also continuing a phase 1b study to evaluate whether pembrolizumab has a role on top of antiretroviral therapy that may replace chemotherapy for patients with Kaposi sarcoma who require additional therapy.” – by Jennifer Byrne
Reference:
Uldrick TS, et al. Abstract 2500 Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Disclosures: Uldrick reports research funding to his institution from Bayer, Celgene, Merck and Roche/Genentech; and a provisional patent application regarding methods of treatment for Kaposi sarcoma and Kaposi sarcoma herpesvirus-induced lymphoma using immunomodulatory compounds and biomarkers. Please see the abstract for all other authors’ relevant financial disclosures.