Evaluation of the Safety and Efficacy of Immunotherapy Rechallenge in Patients with Renal Cell Carcinoma

Praful Ravi, Charlene Mantia, Christopher Su, Karl Sorenson, Dean Elhag, Nityam Rathi, Ziad Bakouny, Neeraj Agarwal, Yousef Zakharia, Brian A. Costello, Rana R. McKay, Vivek Narayan, Ajjai Alva, Bradley A. McGregor, Xin Gao, David F. McDermott, Toni K. Choueiri

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Importance: Several immune checkpoint inhibitors (ICIs) are approved for use in patients with metastatic renal cell carcinoma (mRCC), but the efficacy and safety of ICI rechallenge in mRCC is unknown. Objective: To evaluate the safety and efficacy of ICI rechallenge in patients with mRCC. Design, Setting, and Participants: This multicenter, retrospective cohort study included consecutive patients with mRCC from 9 institutions in the US who received at least 2 separate lines of ICI (ICI-1, ICI-2) between January 2012 and December 2019. Exposure: Receipt of an ICI (anticytotoxic T-lymphocyte-associated protein 4, anti-programmed cell death protein 1, or anti-programmed cell death ligand 1), alone or in combination with other therapies, in at least 2 separate lines of therapy for mRCC. Main Outcomes and Measures: Investigator-assessed best overall response and immune-related adverse events. Results: A total of 69 patients were included. Median (range) age at diagnosis of mRCC was 61 (36-86) years. Of these, 50 were men and 19 were women. The most common therapies received at ICI-1 were single-agent ICI (n = 27 [39%]) or ICI in combination with targeted therapy (n = 29 [42%]), while at ICI-2, the most common therapies were single-agent ICI (n = 26 [38%]) or dual ICI (n = 22 [32%]). Most patients discontinued ICI-1 owing to disease progression (n = 50 [72%]) or toxic effects (n = 16 [23%]). The overall response rates at ICI-1 and ICI-2 were 37% and 23%, respectively. The likelihood of a response at ICI-2 was greatest among patients who had previously responded to ICI-1 (7 of 24 [29%]), although responses at ICI-2 were seen in those who had progressive disease as their best response following ICI-1 (3 of 14 [21%]) as well as in those who received single-agent ICI at ICI-2 (7 of 23 [30%]). Grade 3 or higher immune-related adverse events were seen in 18 patients (26%) and 11 patients (16%) at ICI-1 and ICI-2, respectively. There were no treatment-related deaths. Conclusions and Relevance: The findings of this multicenter cohort study suggest that ICI rechallenge in patients with mRCC may be safe and reasonably efficacious, with an overall response rate of 23%. Data from prospective studies are needed to validate these findings and determine the role of sequential ICI regimens in treatment of mRCC.

Original languageEnglish (US)
Pages (from-to)1606-1610
Number of pages5
JournalJAMA Oncology
Issue number10
StatePublished - Oct 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Evaluation of the Safety and Efficacy of Immunotherapy Rechallenge in Patients with Renal Cell Carcinoma'. Together they form a unique fingerprint.

Cite this