Patient-Reported Outcomes for Cancer Patients Receiving Checkpoint Inhibitors: Opportunities for Palliative Care-A Systematic Review.

CONTEXT: Immune checkpoint inhibitors (ICIs) are increasingly used to treat a variety of cancers, but comparatively little is known about patient-reported outcomes (PROs) and health-related quality of life (HRQoL) among patients receiving these novel therapies. OBJECTIVES: We performed a systematic review to examine PROs and HRQoL among cancer patients receiving ICIs as compared to other anticancer therapies. METHODS: We systematically searched PubMed, CINAHL, Embase, Web of Science, and Scopus, using search terms representing ICIs, PROs, and HRQoL on August 10, 2018. Eligible articles were required to involve cancer patients treated with ICIs and to report PROs and/or HRQoL data. RESULTS: We screened 1453 references and included 15 publications representing 15 randomized controlled trials in our analysis. Studies included several cancer types (melanoma, lung cancer, genitourinary cancer, and head/neck cancer), used four different ICIs (nivolumab, pembrolizumab, atezolizumab, and ipilimumab), and compared ICIs to a wide range of therapies (chemotherapy, targeted therapies, other immunotherapy strategies, and placebo). Studies used a total of seven different PROs to measure HRQOL, most commonly the European Organisation for the Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) (n = 12, 80%). PRO data were reported in a variety of formats and at a variety of time points throughout treatment, which made direct comparison challenging. Some trials (n = 11, 73%) reported PROs on specific symptoms. In general, patients receiving ICIs had similar-to-improved HRQoL and experiences when compared to other therapies. CONCLUSION: Despite the broad clinical trials experience of ICI therapies across cancer types, relatively few randomized studies reported PROs and patient HRQoL data. Available data suggest that ICIs are well tolerated in terms of HRQoL compared to other anticancer therapies although the conclusions are limited by the heterogeneity of trial designs and outcomes. Currently used instruments may fail to capture important symptomatology unique to ICIs, underscoring a need for PROs designed specifically for ICIs.

Severe hemophagocytic lymphohistiocytosis in a melanoma patient treated with ipilimumab + nivolumab.

BACKGROUND: Treatment of metastatic melanoma patients with immune checkpoint inhibitors is an important standard of care. Side effects are due to immune activation, can affect virtually all organ systems, and are occasionally severe. Although hematologic toxicity has been reported, we present a case of hemophagocytic lymphohistiocytosis (HLH) due to immune checkpoint inhibitor therapy. CASE PRESENTATION: A patient with metastatic melanoma was treated with one course of ipilimumab + nivolumab and presented 3 weeks later with severe anemia and hyperferritinemia. A bone marrow biopsy revealed necrotic tumor cells, infiltrating T cells, and hemophagocytosis. The patient was treated with high-dose steroids; 12 months later, the patient remains off all therapy and in complete remission of both HLH and metastatic melanoma. CONCLUSIONS: The hemophagocytic syndromes are attributable to dysregulated immune activation and share pathophysiologic mechanisms with immune activation from checkpoint inhibitors. Increasing use of regimens that include immune checkpoint inhibition require vigilant monitoring for immune-activating side effects as they can occasionally be life threatening, as in this case of HLH.