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PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIV
Diwakar Davar1, Melissa Wilson1, Chelsea Pruckner1
1Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA.
Abstract:
On the basis of remarkable antitumor activity, programmed death receptor-1 (PD-1) inhibitors pembrolizumab and nivolumab were approved for the treatment of advanced melanoma in the second-line setting following progression on either CTLA-4 inhibitor ipilimumab or BRAF/MEK inhibitors (for BRAF mutated melanoma). Given hypothesized risk of triggering exacerbations of autoimmune diseases and/or chronic viral infections, clinical trials (including regulatory studies) evaluating checkpoint blocking antibodies PD-1 and CTLA-4 have excluded patients with autoimmune diseases, chronic hepatitis B/C virus (HBV/HCV), and/or human immunodeficiency virus (HIV) infections. Herein, we describe two patients with advanced melanoma and concomitant HCV/HIV infections treated with PD-1 inhibitor pembrolizumab. Patient 2 with HIV/HCV coinfection progressed after 2 doses of pembrolizumab. Patient 1 who had HCV alone was treated with pembrolizumab with initial partial response. HCV viral load remained stable after 9 cycles of pembrolizumab following which 12-week course of HCV-directed therapy was commenced, resulting in prompt reduction of HCV viral load below detectable levels. Response is ongoing and HCV viral load remains undetectable. In both patients, no significant toxicities were observed when pembrolizumab was initiated. We argue for the further investigation of checkpoint inhibition in cancer patients with underlying chronic viral infections in the context of carefully designed clinical trials.
Insights
Programmed death receptor-1 (PD-1) inhibitors show promise for advanced melanoma patients with chronic viral infections like hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Further clinical trials are warranted to explore this treatment approach.
Area of Science:
- Oncology
- Immunology
- Infectious Diseases
Background:
- Programmed death receptor-1 (PD-1) inhibitors are approved for advanced melanoma.
- Patients with autoimmune diseases and chronic viral infections (hepatitis B/C virus [HBV/HCV], human immunodeficiency virus [HIV]) are typically excluded from clinical trials.
- The safety and efficacy of PD-1 inhibitors in these patient populations remain largely unexplored.
Purpose of the Study:
- To describe the outcomes of two patients with advanced melanoma and concomitant HCV/HIV infections treated with the PD-1 inhibitor pembrolizumab.
- To assess the safety and tolerability of pembrolizumab in this patient cohort.
- To advocate for further investigation of PD-1 inhibitors in cancer patients with chronic viral infections.
Main Methods:
- Case report of two patients with advanced melanoma and concurrent HCV/HIV infections.
- Treatment with PD-1 inhibitor pembrolizumab.
- Monitoring of melanoma response and viral load.
Main Results:
- One patient with HCV alone achieved a partial response and maintained undetectable HCV viral load after concurrent HCV-directed therapy.
- One patient with HIV/HCV coinfection progressed after two doses of pembrolizumab.
- No significant toxicities were observed in either patient upon initiation of pembrolizumab.
Conclusions:
- Pembrolizumab may be a viable treatment option for advanced melanoma patients with chronic viral infections.
- Carefully designed clinical trials are needed to further evaluate checkpoint inhibition in this population.
- The exclusion criteria for PD-1 inhibitor trials may be too restrictive.
