PD-1 blockade with nivolumab in endemic Kaposi sarcoma

Delyon, Julie; Bizot, Alexandra; Battistella, Maxime; Madelaine, Isabelle; Vercellino, Laëtitia; Lebbe, Célèste

doi:10.1093/annonc/mdy006

Cited by 36 publications

(33 citation statements)

References 5 publications

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“…No serious toxicity above grade 2 was observed in the study, and the most common side effects were fatigue, muscle aches and pruritus. Similar results were published in two cases of HIV-negative KS treated with nivolumab 49 . The authors’ publication supports our provocative findings that PD-1 checkpoint blockade could have a therapeutic role in HIV-KS even in the presence of weak or no PD-L1 tumour expression in a similar way that good responses are observed in other virally induced tumours such as polyomavirus (MCPyV)-associated Merkel cell carcinoma 50 .…”

Section: Recent Advancessupporting

confidence: 86%

Recent advances in HIV-associated Kaposi sarcoma

et al. 2019

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Kaposi sarcoma (KS) is a mesenchymal tumour caused by KS-associated herpesvirus and is an AIDS-defining illness. Despite a decline in incidence since the introduction of combination anti-retroviral therapy, KS remains the most common cancer in people living with HIV in sub-Saharan Africa, where it causes significant morbidity and mortality. This review reflects on recent epidemiological data as well as current management, unmet needs and future perspectives in the treatment of HIV-associated KS with particular emphasis on the potential role of immune checkpoint inhibitors.

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Section: Recent Advancessupporting

confidence: 86%

Recent advances in HIV-associated Kaposi sarcoma

et al. 2019

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“…Indeed, PDL1 and PD1 are expressed in HIV-positive KS tissue samples 237 , including samples derived from patients on cART with well-controlled HIV and high CD4 cell counts 238 . Pilot studies of the use of immune checkpoint inhibitors in KS have been promising both in patients with HIV 239 and in patients who are HIV seronegative 240 .…”

Section: Discussionmentioning

confidence: 99%

Kaposi sarcoma

Cesarman

Damania

Krown³

et al. 2019

Nat Rev Dis Primers

453

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Kaposi sarcoma (KS) gained public attention as an AIDS-defining malignancy; its appearance on the skin was a highly stigmatizing sign of HIV infection during the height of the AIDS epidemic. The widespread introduction of effective antiretrovirals to control HIV by restoring immunocompetence reduced the prevalence of AIDS-related KS, although KS does occur in individuals with well-controlled HIV infection. KS also presents in individuals without HIV infection in older men (classic KS), in sub-Saharan Africa (endemic KS) and in transplant recipients (iatrogenic KS). The aetiologic agent of KS is KS herpesvirus (KSHV; also known as human herpesvirus-8), and viral proteins can induce KS-associated cellular changes that enable the virus to evade the host immune system and allow the infected cell to survive and proliferate despite viral infection. Currently, most cases of KS occur in sub-Saharan Africa, where KSHV infection is prevalent owing to transmission by saliva in childhood compounded by the ongoing AIDS epidemic. Treatment for early AIDS-related KS in previously untreated patients should start with the control of HIV with antiretrovirals, which frequently results in KS regression. In advanced-stage KS, chemotherapy with pegylated liposomal doxorubicin or paclitaxel is the most common treatment, although it is seldom curative. In sub-Saharan Africa, KS continues to have a poor prognosis. Newer treatments for KS based on the mechanisms of its pathogenesis are being explored.

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“…Retrospective reports have described responses to anti−PD-1 therapy in HIV-associated and endemic KS. 37,38 Prospective evaluation is warranted to evaluate the efficacy of anti−PD-1 monoclonal antibodies for KS. To date, tumor regression was noted in 5 of 6 participants with relapsed or refractory KS, although this did not meet criteria for partial response at the time of analysis.…”

Section: Discussionmentioning

confidence: 99%

Assessment of the Safety of Pembrolizumab in Patients With HIV and Advanced Cancer—A Phase 1 Study

et al. 2019

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; for the Cancer Immunotherapy Trials Network (CITN)-12 Study Team IMPORTANCE Anti−PD-1 (anti−programmed cell death 1) and anti−PD-L1 (anti−programmed cell death ligand 1) regimens are preferred therapies for many cancers, including cancers associated with HIV. However, patients with HIV were excluded from most registered trials. OBJECTIVE The primary objective was to evaluate the safety of pembrolizumab in people with HIV and advanced cancer; the secondary objective was to evaluate tumor responses. DESIGN, SETTING, AND PARTICIPANTS Open-label, nonrandomized, phase 1 multicenter study conducted at 7 Cancer Immunotherapy Trials Network sites. Patients with HIV and advanced cancer as well as a CD4 count greater than or equal to 100 cells/μL, antiretroviral therapy (ART) for 4 or more weeks, and an HIV viral load of less than 200 copies/mL were eligible. Exclusion criteria included uncontrolled hepatitis B or C infection, active immunosuppressive therapy, or a history of autoimmune disease requiring systemic therapy. INTERVENTIONS Pembrolizumab, 200 mg, administered intravenously every 3 weeks for up to 35 doses in 3 CD4 count−defined cohorts. Participants continued ART. MAIN OUTCOMES AND MEASURES Safety and tolerability were assessed using current NCI Common Terminology Criteria for Adverse Events. Immune-related adverse events grade 2 or higher were considered immune-related events of clinical interest (irECI). Tumor responses were evaluated using standard tumor-specific criteria. RESULTS Thirty participants (28 men and 2 women; median [range] age, 57 [39-77] years) were enrolled from April 2016 through March 2018; 6 had Kaposi sarcoma (KS), 5 had non-Hodgkin lymphoma (NHL), and 19 had non−AIDS-defining cancers. Safety was observed over 183 cycles of treatment with pembrolizumab. Most treatment-emergent adverse events at least possibly attributed to pembrolizumab were grade 1 or 2 (n = 22), and 20% (n = 6) were grade 3. The irECI included hypothyroidism (6 participants), pneumonitis (3 participants), rash (2 participants), an elevated aminotransferase/alanine aminotransferase level (1 participant), and a musculoskeletal event (1 participant). One participant with pretreatment KS herpesvirus (KSHV) viremia developed a polyclonal KSHV-associated B-cell lymphoproliferation and died. HIV was controlled in all participants. Increases in CD4 count were not statistically significant (median increase, 19 cells/μL; P = .18). Best tumor responses included complete response (lung, 1 patient), partial response (NHL, 2 patients), stable disease for 24 weeks or more (KS, 2 patients), stable disease for less than 24 weeks (15 patients), and progressive disease (8 patients); 2 patients were not evaluable. CONCLUSIONS AND RELEVANCE Pembrolizumab has acceptable safety in patients with cancer, HIV treated with ART, and a CD4 + T-cell count of greater than 100 cells/μL but may be associated with KSHV-associated B-cell lymphoproliferation. Clinical benefit was noted in lung cancer, NHL, and KS. Anti−PD-1 therapy is appropriate for US ...

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PD-1 blockade with nivolumab in endemic Kaposi sarcoma

Cited by 36 publications

References 5 publications

Recent advances in HIV-associated Kaposi sarcoma

Recent advances in HIV-associated Kaposi sarcoma

Kaposi sarcoma

Assessment of the Safety of Pembrolizumab in Patients With HIV and Advanced Cancer—A Phase 1 Study

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