2 (S0137). - Comparative Study of Vedolizumab and Infliximab Treatment in Patients With Immune-Mediated Diarrhea and Colitis

Fangwen Zou, MD¹, Amishi Y. Shah, MD², Isabella C. Glitza, MD², David Richards, MD³, Anusha Shirwaikar Thomas, MD², Yinghong Wang, MD, PhD²; ¹University of Texas MD Anderson Cancer Center, Houton, TX; ²University of Texas MD Anderson Cancer Center, Houston, TX; ³MD Anderson Cancer Center, Houston, TX

Introduction: Immune-mediated diarrhea and colitis (IMDC) may limit immune checkpoint inhibitors (ICIs) treatment. Current treatment for IMDC uses steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT = infliximab or vedolizumab add-on) if steroid refractory. We aimed to compare the efficacy of SIT on IMDC and the impact on cancer outcomes.

Methods: We performed a retrospective cohort study of patients with IMDC who received SIT following steroid from 6/2016 to 3/2020. Patient’s demographics, clinical variables, and overall survival data were collected and analyzed.

Results: A total of 150 patients were enrolled, with a median age of 64, 69% male and 97% Caucasian. The most common cancer types were genitourinary cancer and melanoma (total > 70%). In this cohort, 61 received vedolizumab alone, 71 infliximab alone and 18 received both. In comparison to infliximab alone group, patients on vedolizumab alone had a shorter steroid treatment (35 vs 50 days, P< 0.001), less steroid tapering attempts (1 vs 2, P< 0.001), and shorter duration of hospital stay (11 vs 14 days, P=0.025). Vedolizumab was often administered ≥3 doses, while infliximab was mostly limited to 1-2 doses (P< 0.001). The efficacy of achieving clinical remission from initial IMDC was equivalent around 88% between the two groups. Vedolizumab group had significantly lower IMDC recurrence than infliximab (13% vs 28%, P=0.018), although with a slight delay of clinical response (17 vs 10 days, P=0.003).
Factors associated with higher IMDC recurrence included longer durations of ICI treatment (P=0.018), colitis symptoms (P=0.025), and steroid use (P=0.035). In addition, delayed introduction of SIT, and infliximab use alone were also associated with more IMDC recurrence. In contrast, multiple doses of SIT (≥3 doses) was significantly associated with lower IMDC recurrence (P=0.032). Furthermore, vedolizumab alone (P=0.042), higher doses of SIT (P=0.026), and less steroid tapering attempts (P=0.019) were all associated with favorable overall survival (OS).

Discussion: IMDC is a common irAE associated with ICI. Optimal management strategy of IMDC remains to be established. Compared to infliximab, vedolizumab therapy can significantly improve the disease course of IMDC, reduce the steroid exposure, deliver equal efficacy of clinical remission, lower the IMDC recurrence and increase the long term overall survival. Future prospective randomized trial is still merited for further clarification.


Table 1. Clinical characteristics stratified by SIT used (N=132).


Table 2. Univariate Logistic Regression Analysis for Risk Factors of IMDC Recurrence.


Figure 1. Overall Survival (OS) from IMDC, between (A)Vedolizumab used alone and Infliximab used alone; (B) Steroid tapering attempts ≤2 and steroid tapering attempts >2.

Disclosures:
Fangwen Zou indicated no relevant financial relationships.
Amishi Shah indicated no relevant financial relationships.
Isabella Glitza indicated no relevant financial relationships.
David Richards indicated no relevant financial relationships.
Anusha Shirwaikar Thomas indicated no relevant financial relationships.
Yinghong Wang indicated no relevant financial relationships.