Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis
Abu-Sbeih, Hamzah; Ali, Faisal S.; Patel, Sandipkumar; Otterson, Gregory A.; Kendra, Kari; Ricciuti, Biagio; Chiari, Rita; De Giglio, Andrea; Sleiman, Joseph; Funchain, Pauline; Wills, Beatriz; Zhang, Jiajia; Naidoo, Jarushka; Philpott, Jessica; Gao, Jianjun; Subudhi, Sumit K.; Wang, Yinghong
PURPOSE: Immune checkpoint inhibitor (ICI) therapy often is suspended because of immune-mediated diarrhea and colitis (IMDC). We examined the rate of and risk factors for IMDC recurrence after ICI resumption. METHODS: This retrospective multicenter study examined patients who resumed ICI therapy after improvement of IMDC between January 2010 and November 2018. Univariable and multivariable logistic regression analyses assessed the association of clinical covariates and IMDC recurrence. RESULTS: Of the 167 patients in our analysis, 32 resumed an anti–cytotoxic T-cell lymphocyte-4 (CTLA-4) agent, and 135 an anti–programmed cell death 1 or ligand 1 (PD-1/L1) agent. The median age was 60 years (interquartile range [IQR], 50-69 years). The median duration from IMDC to restart of ICI treatment was 49 days (IQR, 23-136 days). IMDC recurred in 57 patients (34%) overall (44% of those receiving an anti–CTLA-4 and 32% of those receiving an anti–PD-1/L1); 47 of these patients (82%) required immunosuppressive therapy for recurrent IMDC, and all required permanent discontinuation of ICI therapy. The median duration from ICI resumption to IMDC recurrence was 53 days (IQR, 22-138 days). On multivariable logistic regression, patients who received anti–PD-1/L1 therapy at initial IMDC had a higher risk of IMDC recurrence (odds ratio [OR], 3.45; 95% CI, 1.59 to 7.69; P = .002). Risk of IMDC recurrence was higher for patients who required immunosuppression for initial IMDC (OR, 3.22; 95% CI, 1.08 to 9.62; P = .019) or had a longer duration of IMDC symptoms in the initial episode (OR, 1.01; 95% CI, 1.00 to 1.03; P = .031). Risk of IMDC recurrence was lower after resumption of anti–PD-1/L1 therapy than after resumption of anti–CTLA-4 therapy (OR, 0.30; 95% CI, 0.11 to 0.81; P = .019). CONCLUSION: One third of patients who resumed ICI treatment after IMDC experienced recurrent IMDC. Recurrence of IMDC was less frequent after resumption of anti–PD-1/L1 than after resumption of anti–CTLA-4
Abu-Sbeih, Hamzah, & Ali, Faisal S., & Patel, Sandipkumar, & Otterson, Gregory A., & Kendra, Kari, & Ricciuti, Biagio, & Chiari, Rita, & De Giglio, Andrea, & Sleiman, Joseph, & Funchain, Pauline, & Wills, Beatriz, & Zhang, Jiajia, & Naidoo, Jarushka, & Philpott, Jessica, & Gao, Jianjun, & Subudhi, Sumit K., & Wang, Yinghong. (October 2019). Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis. Journal of Clinical Oncology, (37:30), p.2738-2745. Retrieved from http://hdl.handle.net/10342/8322
Abu-Sbeih, Hamzah, and Ali, Faisal S., and Patel, Sandipkumar, and Otterson, Gregory A., and Kendra, Kari, and Ricciuti, Biagio, and Chiari, Rita, and De Giglio, Andrea, and Sleiman, Joseph, and Funchain, Pauline, and Wills, Beatriz, and Zhang, Jiajia, and Naidoo, Jarushka, and Philpott, Jessica, and Gao, Jianjun, and Subudhi, Sumit K., and Wang, Yinghong. "Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis". Journal of Clinical Oncology. 37:30. (2738-2745.), October 2019. October 25, 2020. http://hdl.handle.net/10342/8322.
Abu-Sbeih, Hamzah and Ali, Faisal S. and Patel, Sandipkumar and Otterson, Gregory A. and Kendra, Kari and Ricciuti, Biagio and Chiari, Rita and De Giglio, Andrea and Sleiman, Joseph and Funchain, Pauline and Wills, Beatriz and Zhang, Jiajia and Naidoo, Jarushka and Philpott, Jessica and Gao, Jianjun and Subudhi, Sumit K. and Wang, Yinghong, "Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis," Journal of Clinical Oncology 37, no. 30 (October 2019), http://hdl.handle.net/10342/8322 (accessed October 25, 2020).
Abu-Sbeih, Hamzah, Ali, Faisal S., Patel, Sandipkumar, Otterson, Gregory A., Kendra, Kari, Ricciuti, Biagio, Chiari, Rita, De Giglio, Andrea, Sleiman, Joseph, Funchain, Pauline, Wills, Beatriz, Zhang, Jiajia, Naidoo, Jarushka, Philpott, Jessica, Gao, Jianjun, Subudhi, Sumit K., Wang, Yinghong. Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis. Journal of Clinical Oncology. October 2019; 37(30) 2738-2745. http://hdl.handle.net/10342/8322. Accessed October 25, 2020.