Introduction: Patient-reported outcomes (PROs) in cHL are lacking, particularly those collected prospectively in clinical trials. Additionally, patients (pts) with cHL can experience B symptoms, such as fever, night sweats, and weight loss, that can result in decreased HRQoL. KEYNOTE-204 (NCT02684292), an open-label, international, randomized, phase 3 study, demonstrated that the PD-1 inhibitor pembrolizumab exhibited statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs BV in pts with R/R cHL. The current analysis of KEYNOTE-204 evaluated PROs associated with symptoms of R/R cHL (ie, fatigue, nausea/vomiting, and pain) based on the EORTC QLQ-C30 scale and evaluated the effects of pembrolizumab and BV on the presence and resolution of B symptoms.

Methods: Eligible pts were aged ≥18 years, had measurable disease, had ECOG PS 0 or 1, and were R/R cHL after autologous stem cell transplantation (auto-SCT) or were ineligible for auto-SCT. Both BV-naive and BV-exposed pts were eligible. Pts were randomized 1:1 to pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) or BV 1.8 mg/kg IV Q3W and were stratified by prior auto-SCT (yes vs no) and status after first-line therapy (primary refractory vs relapsed <12 months vs relapsed ≥12 months after end of first-line therapy). Symptoms associated with cHL were evaluated as protocol-specified exploratory endpoints using symptom scales of the EORTC QLQ-C30 instrument. EORTC QLQ-C30 was applied electronically at baseline and every 6 weeks up to week 24 and every 12 weeks thereafter. Higher scores on the EORTC QLQ-C30 symptom scales indicated worse symptoms. The analysis population included pts who received ≥1 dose of study treatment and completed ≥1 HRQoL assessment. Both HRQoL and B-symptom data were collected prior to the start date of study drug. Time to first B symptoms was estimated using the Kaplan-Meier method, and treatment differences were evaluated using a stratified Cox proportional hazards model. Rate of resolution of B symptoms was evaluated using the Mantel-Haenszel relative risk test.

Results: Of 304 randomized pts, 296 were included in the PRO analysis (pembrolizumab, 146; BV, 150). Compliance rates were >90% for both groups at baseline and remained high (>80%) at week 24. Mean (SD) baseline EORTC QLQ-C30 scores for fatigue, nausea/vomiting, and pain were 34.9 (24.2), 4.0 (10.3), and 24.6 (25.6), respectively, for the pembrolizumab group and 35.3 (25.6), 8.8 (20.0), and 24.3 (27.5), respectively, for the BV group. At week 24, the mean (SD) baseline EORTC QLQ-C30 fatigue, nausea/vomiting, and pain scores were 21.8 (20.8), 3.6 (10.1), and 12.5 (18.9), respectively, for the pembrolizumab group and 31.4 (17.2), 5.9 (14.0), and 17.4 (20.7), respectively, for the BV group. Improvements in fatigue and pain scores with pembrolizumab were observed at week 6 and remained stable up to week 48; BV exhibited a stable effect up to week 48. No differences were observed over time for pembrolizumab and BV for the nausea/vomiting score. Of 300 pts treated, 78 (pembrolizumab, 42; BV, 36) experienced B symptoms at baseline. Of these 78 pts, 33 (42.3%), 63 (80.8%), and 26 (33.3%) exhibited fever, night sweats, and weight loss, respectively. Of pts who did not experience B symptoms at baseline, 10/106 (9.4%) in the pembrolizumab group and 14/116 (12.1%) in the BV group had symptoms during treatment; median time to first B symptom was not reached in either group (hazard ratio 0.44 [95% CI 0.18-1.04]; two-sided P=0.062). For pts who had B symptoms at baseline, 40/42 (95.2%) in the pembrolizumab group and 27/36 (75.0%) in the BV group experienced resolution of symptoms during the study (risk ratio 1.27 [95% CI 1.05-1.52]; two-sided P=0.013).

Conclusion: In pts with R/R cHL, pembrolizumab monotherapy demonstrated early and sustained improvement over BV in HRQoL fatigue and pain measures associated with cHL that were stable over time, whereas the nausea/vomiting measure was stable over time for both pembrolizumab and BV. Additionally, B symptoms were more likely to resolve in pembrolizumab vs BV-treated pts. Taken together, these data along with clinically meaningful improvements in PFS support pembrolizumab as a preferred treatment option for pts whose disease relapses after auto-SCT or who are ineligible for auto-SCT.

Disclosures

Zinzani:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ramchandren:Seattle Genetics, Sandoz-Novartis, Pharmacyclics, an AbbVie Company, Janssen, Bristol-Myers Squibb: Consultancy; Merck, Seattle Genetics, Janssen, Genentech: Research Funding. Santoro:Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau; Arqule, Sanofi: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees. Paszkiewicz-Kozik:Roche, Takeda, Celgene: Other: Travel/Accommodations/Expenses. Gasiorowski:MSD, Takeda, Novartis, AbbVie: Honoraria. Johnson:Roche/Genentech, Merck: Honoraria; AbbVie: Research Funding; Roche/Genentech, Merck, Bristol-Myers Squibb, AbbVie: Consultancy. Perini:Janssen, Takeda: Honoraria; AbbVie, Janssen: Speakers Bureau. Dickinson:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck Sharp & Dohme: Consultancy; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. McDonald:venetoclax advisory board in South Africa (in CLL context): Consultancy; Alberts Cellular Therapy: Current Employment. Ozcan:Janssen: Other: Travel support, Research Funding; F. Hoffmann-La Roche Ltd: Other: Travel support, Research Funding; Bayer: Research Funding; AbbVie: Other: Travel support, Research Funding; MSD: Research Funding; Archigen Biotech: Research Funding; Celgene: Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding; Amgen: Honoraria, Other: Travel support; Bristol Myers Squibb: Other: Travel support; Jazz Pharmaceuticals: Other; Sanofi: Other; Abdi Ibrahim: Other. Sekiguchi:Ono, A2 Healthcare, Astellas, Janssen, Merck Sharp & Dohme, Otsuka, Pfizer, PPD-SNBL, Sumitomo Dainippon, Daiichi Sankyo, and Bristol-Myers Squibb: Research Funding. Raut:Merck & Co., Inc.: Current Employment. Giezek:Merck & Co., Inc.: Current Employment, Current equity holder in publicly-traded company. Nahar:Merck Sharp & Dohme, Corp., a subsididary of Merck & Co., Inc., Kenlworth, NJ, USA: Current Employment. Kuruvilla:Merck: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy; AstraZeneca Pharmaceuticals LP: Honoraria, Research Funding; Celgene Corporation: Honoraria; Bristol-Myers Squibb Company: Consultancy; TG Therapeutics: Honoraria; Novartis: Honoraria; Antengene: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria.

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2020 by The American Society of Hematology
2020
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