Clinical Characterization of Immunotherapy-Related Pruritus Among Patients Seen in 2 Oncodermatology Clinics

Immunotherapies are landmark disease-modifying agents in cancer but have the potential to cause adverse events that can lead to treatment interruptions, decreased quality of life (QOL), or morbidity.¹ Immunotherapy agents include monoclonal antibodies that target downregulators or checkpoints of the immune response, including cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), programmed cell death 1 (PD1), and programmed death ligand 1 (PD-L1), activating the immune system against tumor cells. Pruritus occurs in 14% to 47% of patients treated with immune checkpoint inhibitors and can range in severity from mild and localized to debilitating and widespread in 1% to 3% of patients.² Pruritus in various dermatologic conditions is associated with lower QOL,³ but to our knowledge the repercussions of immunotherapy-related pruritus among patients with cancer have not been reported.

Patients referred to the oncodermatology clinics at Memorial Sloan Kettering Cancer Center in New York City and the University of Naples Federico II in Naples, Italy, for pruritus attributed to immunotherapy between December 1, 2014, and November 30, 2017, were given the ItchyQoL pruritus assessment, visual analog scale, and body distribution diagram. This study was approved by Memorial Sloan Kettering Cancer Center’s Institutional Review Board, and written informed consent was obtained from all participants. ItchyQoL is validated to assess QOL regarding pruritus symptoms, functional status, and emotional well-being. Each ItchyQoL item is scored from 1 to 5, with higher scores indicating greater burden on QOL.⁴ ItchyQoL is reported as a single score consisting of the mean of the responses to all the items. In the visual analog scale, participants rate their degree of itch on a 100-mm horizontal visual analog scale; possible scores range from 0 to 100, with a score of 0 indicating no itch and 100, extreme itch. Relevant clinical and demographic data were abstracted from electronic medical records. Pruritus was graded by following the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.⁵ Questionnaire responses and patient data were analyzed using SPSS, version 24 (IBM Corp); a 2-sided P < .05 was considered statistically significant.

Seventy-nine patients evaluated by a dermatologist for pruritus attributed to immunotherapy were included; data were unavailable on pruritus grade, number of therapy cycles, and body distribution diagram for 2 patients. The mean (SD) age of patients was 63 (13) years, and 51 (65%) were male (Table). The primary cancer diagnosis was genitourinary in 28 patients (35%), melanoma in 16 (20%), and gastrointestinal in 12 (15%). Twenty-five patients (32%) received a diagnosis of pruritus in normal-appearing skin, and 36 (46%) presented with pruritus and a maculopapular eruption. Forty-nine patients (64%) received a diagnosis of grade 2 or 3 pruritus.

The mean (SD) ItchyQoL score was 2.29 (0.79), with a higher mean (SD) score among female compared with male patients (2.53 [0.80] vs 2.16 [0.77]; P = .04). Patients scored highest on the symptom domain (mean [SD] score, 2.46 [0.75]), followed by function (2.31 [0.92]) and emotion (2.16 [0.95]; P < .001). The median patient-rated degree of itch was 72 (interquartile range, 47-82) of 100 on a visual analog scale. Forty-two of 77 patients presented within the first 6 cycles of therapy (range of cycles, 1-58). The most common sites of pruritus included the trunk, and the least affected sites included the plantar feet, anterior neck, and genitalia (Figure). There was no significant difference in demographic characteristics, number of therapy cycles before presentation, pruritus severity, or QOL between patients with pruritus alone and patients with a coexisting eruption.

Pruritus related to immunotherapy is a frequent adverse event that is associated with lower patient QOL. Because the patients described herein were referred to an oncodermatology clinic, they likely represent patients with severe pruritus or pruritus that did not respond to oncologists’ interventions. Accordingly, severe (CTCAE grade 3) pruritus was common, with a mean ItchyQoL score greater than that found in patients receiving hemodialysis who reported chronic itch (2.29 vs 2.00).⁶ Immunotherapy-related pruritus has been described to involve the scalp,² but our survey suggests anatomical involvement of the torso and extremities, with relative sparing of the head, neck, and acral areas.

There was no significant difference in how pruritus affected QOL between patients with and without a skin eruption, suggesting that pruritus without an eruption deserves attention and treatment in order to maintain QOL.

Immunotherapy-related pruritus represents a substantial burden on QOL in patients with cancer who are referred to a dermatologist. It demands attention and treatment even in normal-appearing skin given its association with reduced QOL and its potential to limit consistent administration of immunotherapy. Additional research is warranted to develop rational, pruritus-specific therapies that do not interfere with the activity of immunotherapies.

Accepted for Publication: October 14, 2018.

Corresponding Author: Mario E. Lacouture, MD, Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 16 E 60th St, Outpatient Center, Ste 407, Room 4312, New York, NY 10022 (lacoutum@mskcc.org).

Published Online: December 12, 2018. doi:10.1001/jamadermatol.2018.4560

Author Contributions: Mr Phillips and Dr Lacouture had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Phillips, Freites-Martinez, Wu, Chan, Hellmann, Lacouture.

Acquisition, analysis, or interpretation of data: Phillips, Freites-Martinez, Wu, Chan, Fabbrocini, Hellmann, Lacouture.

Drafting of the manuscript: Phillips, Freites-Martinez, Lacouture.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Phillips, Chan.

Obtained funding: Lacouture.

Administrative, technical, or material support: Phillips, Freites-Martinez, Wu, Hellmann, Lacouture.

Supervision: Freites-Martinez, Wu, Fabbrocini, Hellmann, Lacouture.

Conflict of Interest Disclosures: Dr Hellmann reported serving as a consultant to Merck, Bristol-Myers Squibb, AstraZeneca, Genentech/Roche, Janssen, Nektar, Syndax Pharmaceuticals, Mirati Therapeutics, and Shattuck Labs and receiving research funding from Bristol-Myers Squibb. Dr Lacouture reported serving as a consultant to Merck, Roche, AbbVie, Quintiles, NCODA, Boehringer Ingelheim, AstraZeneca, Helsinn Healthcare, Allergan, Amgen, E. R. Squibb, EMD Serono, Genentech, Legacy Healthcare, Foamix Pharmaceuticals, Adgero Biopharmaceuticals, Janssen, Novartis, Paxman, NovoCure Bristol-Myers Squibb, Galderma, Debio, Pfizer, Silk Therapeutics, Medische Voet, Johnson & Johnson, Seattle Genetics, Bayer, Manner SAS, Menlo Ther, and Lutris and receiving research grants from BERG, Veloce BioPharma, US Biotest, Bristol-Myers Squibb, Genentech/Roche, Paxman, GSK/Novartis, and the RJR Fund. No other disclosures were reported.

Funding/Support: This research was funded in part through grants P30 CA008748 and R25CA020449 from the National Institutes for Health/National Cancer Institute Cancer Center. This research was also funded in part by Beca Excelencia Fundación Piel Sana (Dr Freites-Martinez) and a grant from RJR.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.