P0235 - IL12/23 Blockade Therapy for Refractory Immune Checkpoint Inhibitor Colitis: A Case Series

Sunday, October 24, 2021

3:30 PM – 7:00 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

Anusha Shirwaikar Thomas, MD

University of Texas MD Anderson Cancer Center
Houston, TX, United States

Anusha Shirwaikar Thomas, MD¹, Jennifer McQuade, MD¹, Mehmet Altan, MD², Yinghong Wang, MD, PhD, MS¹
¹University of Texas MD Anderson Cancer Center, Houston, TX; ²MD Anderson Cancer Center, Houston, TX

Introduction: Ustekinumab, a human monoclonal antibody to p40 subunit of interleukin (IL)12/23 is efficacious in the management of severe Crohn’s disease (CD) as demonstrated by the UNITI 1/2 trials.

Immune-mediated colitis (IMC) that resembles inflammatory bowel disease, is an immune related adverse effect of immune checkpoint inhibitors (ICI) that antagonize inhibitory molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1/death-ligand 1 (PD-1/PD-L1).

While optimal evidence based management of this disease process is lacking, medical therapy is limited to corticosteroids, followed by infliximab (IFX), and vedolizumab (VDZ) based on societal guidelines. Fecal microbiota transplantation (FMT) has shown favorable results in aggressive cases.

Case Description/Methods: We present a case series of 10 patients with ≥ grade 2 IMC refractory to IFX and VDZ that were treated with Ustekinumab therapy.

A majority were Caucasian with a median age of 61 years in our sample. Our cohort was equally distributed in regards to gender. A majority had stage 4 malignant melanoma with more than half on combination immunotherapeutic regimens (Figure 1). Endoscopic severity based on Mayo sub-score did not correlate with clinical grade of diarrhea. A majority in our sample had chronic active colitis on histology. All patients remained clinically refractory to therapy with systemic steroids and selective immunosuppression with IFX/VDZ or a combination. 8 patients attained clinical remission with ustekinumab and were alive at last follow up. 5 patients in our cohort received FMT. Of these, 3 responded to ustekinumab. For details please refer to Table 2. Of the 2 patients who did not reach colitis remission, both received targeted therapy for cancer after ICI, one had an underlying diagnosis of ulcerative colitis while the other succumbed to cancer progression.

Discussion:

IMC can recur/persist with secondary non response to selective immunosuppression and termination of the inciting drug

IL12/23 inflammatory pathway may serve as a therapeutic target and alternative to long term steroid dependency in management of IMC refractory to current standard of care therapies.

IL12/23 blockade may be effective in attaining clinical remission in IMC.

A histologic pattern of IMC similar to IBD i.e. chronic active colitis appears to respond to IL 12/23 blockade

The role of IL12/23 antagonists in cancer and the implications for therapeutic inhibition of IL‐12 remain uncertain but need further elucidation.

Figure: Figure 1

Characteristic	Data (N=10)
Highest grade of diarrhea (3-4) – no. (%)	8 (80%)
Highest grade of colitis – no. (%)
0-2	9 (90%)
3-4	1 (10%)
Initial endoscopic findings—no (%)
Ulcers	5 (50%)
Non-ulcer inflammation	2 (20%)
Normal	3 (30%)
Initial histology findings—no (%)
Acute inflammation	2 (20%)
Chronic active inflammation	6 (60%)
Microscopic colitis	2 (20%)
Hospitalizations – no. (%)	8 (80%)
Other treatment of GI adverse event – no. (%)
Steroid	10 (100%)
Infliximab/vedolizumab	10 (100%)
FMT ^A	5 (50%)
Resumed cancer treatment after Rx—no (%)	4 (40%)
Clinical remission at last follow up- n=10	8 (80%)
Endoscopic remission at last follow up—n=5 (%)	4 (80%)
Cancer status at the last follow up –no (%)
Remission	1(10%)
Stable disease	4(40%)
Progression	5(50%)
Mortality	1 (10%)

^A:5 patients received FMT: 1 prior to Ustekinumab, 4 after Ustekinumab . Of these 4, 2 did not respond to Ustekinumab. 2 discontinued the drug due to allergic reactions, and loss of insurance coverage

Table: Table 2. Characteristics of gastrointestinal adverse events

Disclosures:

Anusha Shirwaikar Thomas indicated no relevant financial relationships.

Jennifer McQuade indicated no relevant financial relationships.

Mehmet Altan indicated no relevant financial relationships.

Yinghong Wang: AzurRx pharma – Consultant. Tillotts pharma – Consultant.

Anusha Shirwaikar Thomas, MD¹, Jennifer McQuade, MD¹, Mehmet Altan, MD², Yinghong Wang, MD, PhD, MS¹. P0235 - IL12/23 Blockade Therapy for Refractory Immune Checkpoint Inhibitor Colitis: A Case Series, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.