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Brief Report
May 29, 2020

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

Author Affiliations
  • 1Dana-Farber Cancer Institute, Boston, Massachusetts
  • 2Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • 3University of Michigan, Ann Arbor
  • 4Mayo Clinic, Rochester, Minnesota
  • 5The University of Iowa, Iowa City
  • 6Huntsman Cancer Institute, Salt Lake City, Utah
  • 7University of California, San Diego
  • 8University of Pennsylvania, Philadelphia
  • 9Massachusetts General Hospital, Boston
JAMA Oncol. 2020;6(10):1606-1610. doi:10.1001/jamaoncol.2020.2169
Key Points

Question  What are the safety and efficacy profiles of rechallenge with an immune checkpoint inhibitor (ICI) in patients with metastatic renal cell carcinoma?

Findings  In this cohort study of 69 patients treated between 2012 and 2019, the overall response rate of ICI rechallenge was 23%. In addition, ICI rechallenge was reasonably safe, with 11 patients (16%) experiencing a grade 3 or higher immune-related adverse event.

Meaning  The findings of this cohort study suggest that ICI rechallenge may be safe and reasonably effective for the treatment of patients with metastatic renal cell carcinoma.


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.

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