Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis

Hamzah Abu-Sbeih, Faisal S. Ali, Abdul Rafeh Naqash, Dwight H. Owen, Sandipkumar Patel, Gregory A. Otterson, Kari Kendra, Biagio Ricciuti, Rita Chiari, Andrea De Giglio, Joseph Sleiman, Pauline Funchain, Beatriz Wills, Jiajia Zhang, Jarushka Naidoo, Jessica Philpott, Jianjun Gao, Sumit K. Subudhi, Yinghong Wang

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2738-2745
Number of pages8
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number30
DOIs
StatePublished - Oct 20 2019

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Colitis
Diarrhea
CD274 Antigen
Recurrence
Therapeutics
Odds Ratio
Logistic Models
Cytotoxic T-Lymphocytes
Immunosuppressive Agents
Immunosuppression
Multicenter Studies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis. / Abu-Sbeih, Hamzah; Ali, Faisal S.; Naqash, Abdul Rafeh; Owen, Dwight H.; 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.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 37, No. 30, 20.10.2019, p. 2738-2745.

Research output: Contribution to journalArticle

Abu-Sbeih, H, Ali, FS, Naqash, AR, Owen, DH, Patel, S, Otterson, GA, Kendra, K, Ricciuti, B, Chiari, R, De Giglio, A, Sleiman, J, Funchain, P, Wills, B, Zhang, J, Naidoo, J, Philpott, J, Gao, J, Subudhi, SK & Wang, Y 2019, 'Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 37, no. 30, pp. 2738-2745. https://doi.org/10.1200/JCO.19.00320
Abu-Sbeih, Hamzah ; Ali, Faisal S. ; Naqash, Abdul Rafeh ; Owen, Dwight H. ; 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. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 ; Vol. 37, No. 30. pp. 2738-2745.
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abstract = "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.",
author = "Hamzah Abu-Sbeih and Ali, {Faisal S.} and Naqash, {Abdul Rafeh} and Owen, {Dwight H.} and Sandipkumar Patel and Otterson, {Gregory A.} and Kari Kendra and Biagio Ricciuti and Rita Chiari and {De Giglio}, Andrea and Joseph Sleiman and Pauline Funchain and Beatriz Wills and Jiajia Zhang and Jarushka Naidoo and Jessica Philpott and Jianjun Gao and Subudhi, {Sumit K.} and Yinghong Wang",
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TY - JOUR

T1 - Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis

AU - Abu-Sbeih, Hamzah

AU - Ali, Faisal S.

AU - Naqash, Abdul Rafeh

AU - Owen, Dwight H.

AU - Patel, Sandipkumar

AU - Otterson, Gregory A.

AU - Kendra, Kari

AU - Ricciuti, Biagio

AU - Chiari, Rita

AU - De Giglio, Andrea

AU - Sleiman, Joseph

AU - Funchain, Pauline

AU - Wills, Beatriz

AU - Zhang, Jiajia

AU - Naidoo, Jarushka

AU - Philpott, Jessica

AU - Gao, Jianjun

AU - Subudhi, Sumit K.

AU - Wang, Yinghong

PY - 2019/10/20

Y1 - 2019/10/20

N2 - 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.

AB - 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.

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