P1619 - Diarrhea and Colitis Related to Immune Checkpoint Inhibitor and BRAF/MEK Inhibitor Therapy

Andrew Kuang, MD¹, Wasay Mohajir, DO², Anusha Shirwaikar Thomas, MD³, Yinghong Wang, MD, PhD, MS^3
1Baylor College of Medicine, Houston, TX; ²University of Texas Health Science Center at Houston, Houston, TX; ³University of Texas MD Anderson Cancer Center, Houston, TX

Introduction: Immune checkpoint inhibitor (ICI) use is complicated by GI adverse events (GI AE). Similarly, though not well understood, GI AE are reported with use of serine/threonine-protein kinase B-Raf (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors as targeted therapy in select cancers. We aim to study the characteristics and management of these GI AEs related to BRAF/MEK inhibitors with or without ICI use.

Methods: 255 adult cancer patients were identified who had exposure to both BRAF/MEK inhibitor targeted therapy and ICI between 2016 and 2020. 31 eligible patients had GI AE after exposure to both therapies after excluding other identifiable causes and categorized based on the sequential order of ICI and BRAF/MEK inhibitor therapy. Clinical characteristics, evaluation, treatment, and outcomes were compared.

Results: Of 31 eligible patients, 17 (54.8%) received ICI followed by targeted therapy (ICI-TT) while 14 (45.2%) received targeted therapy followed by ICI (TT-ICI). The median age of patients was 51 years in ICI-TT group and 52 years in TT-ICI group. 52.9% of patients in the ICI-TT group and 57.1% of patients in the TT-ICI group were female. The most common cancer in both groups was melanoma. More patients in the ICI-TT group had grade 3-4 diarrhea and grade 3-4 colitis than patients in the TT-ICI group. Patients in the ICI-TT group also more frequently presented with colonic ulceration on endoscopy and required hospitalization. Patients in the ICI-TT group received more frequent treatment of corticosteroid and selective immunosuppressive therapy (SIT) with infliximab or vedolizumab, however still had higher colitis recurrence leading to more rehospitalization (Table 1).

Discussion: The sequence of blockade of checkpoints and BRAF/MEK in the therapy of advanced malignancies may play a role in the clinical presentation and management of therapy-related GI toxicities. Compared to those who received ICI therapy after BRAF/MEK inhibitor therapy, we observe a more aggressive clinical and endoscopic profile of these toxicities in those that receive targeted therapy after checkpoint blockade, e.g. higher grades of diarrhea and colitis, increased colonic ulceration and hospitalization. Despite increased corticosteroid therapy and SIT, they had higher colitis recurrence leading to more frequent rehospitalization. Further large-scale study is warranted for further clarification.

Table 1. Selected clinical characteristics and therapy outcomes, N=31
Variables	ICI followed by BRAF/MEK, N=17	BRAF/MEK followed by ICI, N=14
Malignancy Type
Melanoma	16 (94.1%)	9 (64.3%)
Endocrine	0 (0.0%)	5 (35.7%)
Lung	1 (5.9%)	0 (0.0%)
Cancer stage 4	16 (94.1%)	14 (100.0%)
Peak CTCAE grade of diarrhea
1-2	5 (29.4%)	10 (71.4%)
3-4	9 (52.9%)	2 (14.3%)
Peak CTCAE grade of colitis
1-2	10 (58.8%)	14 (100.0%)
3-4	7 (41.2%)	0 (0.0%)
Number of patients that received lower endoscopy	10 (58.8%)	11 (78.6%)
Endoscopic finding
Normal	3 (30.0%)	3 (27.3%)
Ulceration	5 (50.0%)	2 (18.2%)
Non-ulcerative inflammation	5 (50.0%)	7 (63.6%)
Number of patients hospitalized for colitis	17 (100.0%)	10 (71.4%)
Number of patients that received PO and/or IV corticosteroids	15 (88.2%)	8 (57.1%)
Number of patients that received SIT1 (infliximab or vedolizumab)	9 (52.9%)	6 (42.9%)
Number of patients with diarrhea or colitis recurrence	8 (47.1%)	1 (7.1%)
Number of patients readmitted for colitis after initial hospitalization	6 (35.3%)	0 (0.0%)

Table: 1 Selective immunosuppressive therapy


Disclosures:
Andrew Kuang indicated no relevant financial relationships.
Wasay Mohajir indicated no relevant financial relationships.
Anusha Shirwaikar Thomas indicated no relevant financial relationships.
Yinghong Wang: AzurRx – Consultant. Tillotts – Consultant.


Andrew Kuang, MD¹, Wasay Mohajir, DO², Anusha Shirwaikar Thomas, MD³, Yinghong Wang, MD, PhD, MS³. P1619 - Diarrhea and Colitis Related to Immune Checkpoint Inhibitor and BRAF/MEK Inhibitor Therapy, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.