Few Patients With ICI-Mediated Mucositis Require Immunosuppression

Findings from a retrospective, descriptive, single-center study of adult patients found that most patients who receive immune checkpoint inhibitors (ICIs), such as CTLA-4, PD-1, and PD-L1, show clinical improvement and even resolution of the immune-related adverse event (irAEs), oral mucositis over time.¹

Investigators also found patients who received anti–CTLA-4 therapy were more likely to have mucositis and other immune-related adverse events than those treated receiving anti–PD-1/L1 therapy (P=.032).1

ICI–mediated mucositis (IMM) can possibly last months after treatment with symptoms ranging from mild to severe. Focusing on patients treated with pembrolizumab (Keytruda), ipilimumab (Yervoy), nivolumab (Opdivo), atezolizumab (Tecentriq), durvalumab (Imfinzi), avelumab (Bavencio), cemiplimab (Libtayo), and tremelimumab, the study included 10,275 patients who were treated with ICIs at The University of Texas MD Anderson Cancer Center. Of those treated with these therapies, 652 developed mucositis between January 2009 to September 2019. Data from five-hundred patients were excluded, leaving 152 patients for the final analysis.

The cohort had a mean age of 60 years at the time of ICI treatment. The population was majority male (51%) and the majority of patients identified as White (72%). Notable, 57% of the cohort received concurrent chemotherapy in addition to ICI therapy. Of the patients assessed, the most common malignancies were melanoma (28%), lung (10%), head and neck (8%), and hematologic (16%). Regarding disease stage, 73% of patients had stage IV disease. Of these studied patients, 78% were treated with a PD-1/L1 inhibitor (n=119), and 22% were treated with a CTLA-4 inhibitor (n=33).

The study found that 88% of patients showed improvement or resolution of mucositis. Of these patients, 92% and 76% taking anti–PD-1/L1 and anti–CTLA-4, respectively, saw improvement (P=.029). The overall median duration to onset mucositis was 91 days (27-174). The median duration to onset for the anti–PD-1/L1 group was 96 days (135-199) and was 73 days (22-119) for the anti–CTLA-4 group (P=.077). The mucositis presented as odynophagia/oral pain (89%), nausea or vomiting (20%), dysphagia (10%), and bleeding (4%). Most mucositis presented were grades 1 and 2 (91%).

Seventeen patients were hospitalized (11%), and the median hospital stay lasted 10 days (6-20). Of these hospitalized patients, 4 required central line replacement due to mucositis, 1 had line–related bloodstream infection, and 6 had compromised nutrition as a result of mucositis requiring either feeding tube support or total parental nutrition.

Thirty-four percent of patients experienced mucositis recurrence with 1.3% requiring rehospitalization. Among the 138 patients who had resolved or improved symptoms, 39% (n=52) had recurrence of mucositis. Of these 52 patients who experienced mucositis recurrence, 79% (n=42) were treated with anti–PD-1/L1 therapy. Duration of symptoms lasted longer in patients who had recurrence with a median of 56 days (21-181) compared with a median of 36 days (15-93) among patients who did not experience recurrence (P=.058). Researchers noticed an association with recurrence in patients with coexisting irAEs (P=.038) and patients requiring immunosuppression for the initial mucositis event (P=.006).

Immunosuppression occurred in 24% of patients with a median symptom duration of 51 days (26-81). Patients who underwent immunosuppression therapy had a median symptom duration of 84 days (46-120) vs 34 days (14-84; P=.002) with no immunosuppressive therapy.

The mean age of patients at ICI initiation was 60 years. Fifty-one percent were male, and 72% were White. The most prevalent baseline risk factors were other concurrent therapies with ICIs (57%), history of smoking (47%), and premucositis immunosuppressant use (24%). The most common cancer types among patients were melanoma (28%), lung/head and neck (18%), genitourinary (17%), and hematologic (16%). Most patients had stage IV disease (73%).

irAEs presented in 64% of patients in addition to mucositis. Additional irAEs were found in 60% of the anti–PD-1/L1 group and 82% of the anti–CTLA-4 group (P=.032). Twenty-five percent of the irAEs were gastrointestinal, including gastritis and enterocolitis. ICI therapy was interrupted in 77% of patients due to irAEs. The all-cause mortality rate was 50%.

Further studies are warranted to investigate risk factors with refractory mucositis, learn more of immunosuppression therapy and its role in treatment, and develop a standard diagnostic for ICI therapy to better optimize clinical benefit in patients with mucositis.

_Reference

_{1. Jacob JS, Dutra BE, Garcia-Rodriguez V, et al. Clinical Characteristics and outcomes of oral mucositis associated with immune checkpoint inhibitors in patients with cancer. J Natl Compr Canc Netw. 2021;19(12):1415-1424. doi:10.6004/jnccn.2020.7697}