Myositis as an adverse event of immune checkpoint blockade for cancer therapy

https://doi.org/10.1016/j.semarthrit.2018.05.006Get rights and content

Abstract

Objectives

Immune checkpoint inhibitors (ICIs) can successfully treat cancer, but their use can be hindered by serious immune-related adverse events. We report six patients receiving ICIs who presented with de novo myositis.

Methods

We identified patients with myositis who were receiving ICIs between January 2004 and September 2016 at The University of Texas MD Anderson Cancer Center.

Results

Six patients developed de novo myositis. The mean age was 64.3 years and five patients were male. Cancer types included melanoma, urothelial carcinoma, renal cell carcinoma, and prostate cancer. ICI regimens included single-agent ipilimumab (n = 1), pembrolizumab (n = 1), or atezolizumab (n = 1); nivolumab and ipilimumab (n = 3). The median time to development of de novo myositis from first infusion was 5.4 weeks (range: 2.1–17.1 weeks). All patients with myositis had elevated levels of creatinine kinase, ranging from 514 to 13,710 U/L. Two of them developed rhabdomyolysis, one with concurrent myocarditis. Five patients were treated with 1–2 mg/kg corticosteroids, with variable response rates; one patient received nonsteroidal anti-inflammatory drugs. Two patients with myositis died as a result of cancer progression.

Conclusion

We found several occurrences of de novo myositis following ICI therapy. These preliminary data suggest that myositis can occur early after onset of ICI therapy with serious adverse outcomes.

Section snippets

Methods

Institutional databases were used to identify cancer patients aged at least 18 years, who had received treatment with ICI (either anti-PD-1 or anti-PD-L1 monotherapy, or combination therapy with anti-PD-1/CTLA-4) at any time between January 2004 and September 2016, to allow for sufficient follow-up. We identified 3016 patients from pharmacy records. Claims data were extracted for all the patients 6 months prior to the first infusion of to the last follow-up or death. International

Results

Six patients with de novo myositis were included (Table). Mean age was 64.3 years [standard deviation (SD) = 11.8 years], and five patients were male. All ICI that were approved during study period (ipilimumab, nivolumab, pembrolizumab, and atezolizumab were associated with at least one case of myositis. Half of the patients with de novo myositis had received combination therapy with ipilimumab and nivolumab.

Discussion

Immune checkpoint inhibitors have shown great promise in the treatment of various cancers, but their use can be hampered by the occurrence of inflammatory and irAE that can be severe. A plethora of irAE have been reported in the literature, which can affect nearly any organ or system, presenting management challenges [14], [15], [39]. Rheumatic irAE have been infrequently documented in clinical trials with a majority of the data coming from case reports and series [22], [40], [41].

Our series

Contribution

Dr. Suarez-Almazor conceived and supervised the study. Dr. Shah designed and carried out the study, extracted and analyzed the data and prepared the first draft of the manuscript. Dr. Tayar reviewed the data for accuracy and consistency and helped analyze the data. Dr. Abdel-Wahab assisted in acquiring the data and carrying out the ground work necessary for implementation of the study. All authors contributed to the composition and revision of the manuscript. All authors read and approved the

Declarations of interest

Dr. Suarez-Almazor reports personal fees from Pfizer, grants from Pfizer, personal fees from Elli Lilly, personal fees from Endo Pharmaceuticals, personal fees from Bristol Myers Squibb, personal fees from Genentech, personal fees from Ardea Pharmaceuticals, outside the submitted work.

Acknowledgments

We thank Erica A. Goodoff of the department of scientific publications at The University of Texas MD Anderson Cancer Center for copyediting the manuscript.

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