Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma

Jing Nie, Chunmeng Wang, Yang Liu, Qingming Yang, Qian Mei, Liang Dong, Xiang Li, Jiejie Liu, Wenjing Ku, Yan Zhang, Meixia Chen, Xiaojing An, Lu Shi, Malcolm V Brock, Jie Bai, Weidong Han

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Abstract

PURPOSE: Anti-programmed death-1 (PD-1) monotherapy induces a high response rate in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but complete remission (CR) is infrequently observed. As decitabine is known to boost T-cell function, we assessed the safety and efficacy of anti-PD-1 camrelizumab alone versus decitabine-primed camrelizumab in patients with relapsed/refractory cHL. METHODS: This two-arm, open-label, phase II study enrolled patients with relapsed/refractory cHL who had received at least two lines of previous therapy. Anti-PD-1 treatment-naïve patients were randomly assigned (1:2) to camrelizumab (200 mg) monotherapy or decitabine (10 mg/d, days 1 to 5) plus camrelizumab (200 mg, day 8) combination therapy every 3 weeks. Patients who were previously treated with anti-PD-1 were assigned combination therapy. Primary end point was CR rate and safety. RESULTS: Overall, 86 patients were enrolled and evaluated for response, with a median follow-up of 14.9 months. In anti-PD-1-naïve patients, CR rate was 32% (six of 19 patients) with camrelizumab monotherapy versus 71% (30 of 42 patients) who were administered decitabine plus camrelizumab (P = .003). At the time of analysis, the response duration rate at 6 months was 76% on camrelizumab monotherapy versus 100% on decitabine plus camrelizumab. For patients who were previously treated with anti-PD-1, 28% achieved CR and 24% partial response after decitabine plus camrelizumab. Ten patients maintained a response at more than 6 months and 81% of responders were estimated to have a response at more than 1 year. For both treatments, the most common adverse events were clinically inconsequential cherry hemangiomas and leukocytopenia that were self-limiting. CONCLUSION: CR rate in patients with relapsed/refractory cHL who were clinically naïve to PD-1 blockade was significantly higher with decitabine plus camrelizumab than with camrelizumab alone. Decitabine plus camrelizumab may reverse resistance to PD-1 inhibitors in patients with relapsed/refractory cHL.

Original languageEnglish (US)
Pages (from-to)1479-1489
Number of pages11
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number17
DOIs
StatePublished - Jun 10 2019

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decitabine
Hodgkin Disease
Antibodies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma. / Nie, Jing; Wang, Chunmeng; Liu, Yang; Yang, Qingming; Mei, Qian; Dong, Liang; Li, Xiang; Liu, Jiejie; Ku, Wenjing; Zhang, Yan; Chen, Meixia; An, Xiaojing; Shi, Lu; Brock, Malcolm V; Bai, Jie; Han, Weidong.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 37, No. 17, 10.06.2019, p. 1479-1489.

Research output: Contribution to journalArticle

Nie, Jing ; Wang, Chunmeng ; Liu, Yang ; Yang, Qingming ; Mei, Qian ; Dong, Liang ; Li, Xiang ; Liu, Jiejie ; Ku, Wenjing ; Zhang, Yan ; Chen, Meixia ; An, Xiaojing ; Shi, Lu ; Brock, Malcolm V ; Bai, Jie ; Han, Weidong. / Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 ; Vol. 37, No. 17. pp. 1479-1489.
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title = "Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma",
abstract = "PURPOSE: Anti-programmed death-1 (PD-1) monotherapy induces a high response rate in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but complete remission (CR) is infrequently observed. As decitabine is known to boost T-cell function, we assessed the safety and efficacy of anti-PD-1 camrelizumab alone versus decitabine-primed camrelizumab in patients with relapsed/refractory cHL. METHODS: This two-arm, open-label, phase II study enrolled patients with relapsed/refractory cHL who had received at least two lines of previous therapy. Anti-PD-1 treatment-na{\"i}ve patients were randomly assigned (1:2) to camrelizumab (200 mg) monotherapy or decitabine (10 mg/d, days 1 to 5) plus camrelizumab (200 mg, day 8) combination therapy every 3 weeks. Patients who were previously treated with anti-PD-1 were assigned combination therapy. Primary end point was CR rate and safety. RESULTS: Overall, 86 patients were enrolled and evaluated for response, with a median follow-up of 14.9 months. In anti-PD-1-na{\"i}ve patients, CR rate was 32{\%} (six of 19 patients) with camrelizumab monotherapy versus 71{\%} (30 of 42 patients) who were administered decitabine plus camrelizumab (P = .003). At the time of analysis, the response duration rate at 6 months was 76{\%} on camrelizumab monotherapy versus 100{\%} on decitabine plus camrelizumab. For patients who were previously treated with anti-PD-1, 28{\%} achieved CR and 24{\%} partial response after decitabine plus camrelizumab. Ten patients maintained a response at more than 6 months and 81{\%} of responders were estimated to have a response at more than 1 year. For both treatments, the most common adverse events were clinically inconsequential cherry hemangiomas and leukocytopenia that were self-limiting. CONCLUSION: CR rate in patients with relapsed/refractory cHL who were clinically na{\"i}ve to PD-1 blockade was significantly higher with decitabine plus camrelizumab than with camrelizumab alone. Decitabine plus camrelizumab may reverse resistance to PD-1 inhibitors in patients with relapsed/refractory cHL.",
author = "Jing Nie and Chunmeng Wang and Yang Liu and Qingming Yang and Qian Mei and Liang Dong and Xiang Li and Jiejie Liu and Wenjing Ku and Yan Zhang and Meixia Chen and Xiaojing An and Lu Shi and Brock, {Malcolm V} and Jie Bai and Weidong Han",
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T1 - Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma

AU - Nie, Jing

AU - Wang, Chunmeng

AU - Liu, Yang

AU - Yang, Qingming

AU - Mei, Qian

AU - Dong, Liang

AU - Li, Xiang

AU - Liu, Jiejie

AU - Ku, Wenjing

AU - Zhang, Yan

AU - Chen, Meixia

AU - An, Xiaojing

AU - Shi, Lu

AU - Brock, Malcolm V

AU - Bai, Jie

AU - Han, Weidong

PY - 2019/6/10

Y1 - 2019/6/10

N2 - PURPOSE: Anti-programmed death-1 (PD-1) monotherapy induces a high response rate in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but complete remission (CR) is infrequently observed. As decitabine is known to boost T-cell function, we assessed the safety and efficacy of anti-PD-1 camrelizumab alone versus decitabine-primed camrelizumab in patients with relapsed/refractory cHL. METHODS: This two-arm, open-label, phase II study enrolled patients with relapsed/refractory cHL who had received at least two lines of previous therapy. Anti-PD-1 treatment-naïve patients were randomly assigned (1:2) to camrelizumab (200 mg) monotherapy or decitabine (10 mg/d, days 1 to 5) plus camrelizumab (200 mg, day 8) combination therapy every 3 weeks. Patients who were previously treated with anti-PD-1 were assigned combination therapy. Primary end point was CR rate and safety. RESULTS: Overall, 86 patients were enrolled and evaluated for response, with a median follow-up of 14.9 months. In anti-PD-1-naïve patients, CR rate was 32% (six of 19 patients) with camrelizumab monotherapy versus 71% (30 of 42 patients) who were administered decitabine plus camrelizumab (P = .003). At the time of analysis, the response duration rate at 6 months was 76% on camrelizumab monotherapy versus 100% on decitabine plus camrelizumab. For patients who were previously treated with anti-PD-1, 28% achieved CR and 24% partial response after decitabine plus camrelizumab. Ten patients maintained a response at more than 6 months and 81% of responders were estimated to have a response at more than 1 year. For both treatments, the most common adverse events were clinically inconsequential cherry hemangiomas and leukocytopenia that were self-limiting. CONCLUSION: CR rate in patients with relapsed/refractory cHL who were clinically naïve to PD-1 blockade was significantly higher with decitabine plus camrelizumab than with camrelizumab alone. Decitabine plus camrelizumab may reverse resistance to PD-1 inhibitors in patients with relapsed/refractory cHL.

AB - PURPOSE: Anti-programmed death-1 (PD-1) monotherapy induces a high response rate in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but complete remission (CR) is infrequently observed. As decitabine is known to boost T-cell function, we assessed the safety and efficacy of anti-PD-1 camrelizumab alone versus decitabine-primed camrelizumab in patients with relapsed/refractory cHL. METHODS: This two-arm, open-label, phase II study enrolled patients with relapsed/refractory cHL who had received at least two lines of previous therapy. Anti-PD-1 treatment-naïve patients were randomly assigned (1:2) to camrelizumab (200 mg) monotherapy or decitabine (10 mg/d, days 1 to 5) plus camrelizumab (200 mg, day 8) combination therapy every 3 weeks. Patients who were previously treated with anti-PD-1 were assigned combination therapy. Primary end point was CR rate and safety. RESULTS: Overall, 86 patients were enrolled and evaluated for response, with a median follow-up of 14.9 months. In anti-PD-1-naïve patients, CR rate was 32% (six of 19 patients) with camrelizumab monotherapy versus 71% (30 of 42 patients) who were administered decitabine plus camrelizumab (P = .003). At the time of analysis, the response duration rate at 6 months was 76% on camrelizumab monotherapy versus 100% on decitabine plus camrelizumab. For patients who were previously treated with anti-PD-1, 28% achieved CR and 24% partial response after decitabine plus camrelizumab. Ten patients maintained a response at more than 6 months and 81% of responders were estimated to have a response at more than 1 year. For both treatments, the most common adverse events were clinically inconsequential cherry hemangiomas and leukocytopenia that were self-limiting. CONCLUSION: CR rate in patients with relapsed/refractory cHL who were clinically naïve to PD-1 blockade was significantly higher with decitabine plus camrelizumab than with camrelizumab alone. Decitabine plus camrelizumab may reverse resistance to PD-1 inhibitors in patients with relapsed/refractory cHL.

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DO - 10.1200/JCO.18.02151

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