Impact of concomitant H1 antihistamine administered during initiation of immune checkpoint inhibitor therapy on survival outcome and safety in patients with advanced primary lung cancer.

Abstract

e20532 Background: Antihistamines alleviate the side effects of antitumor drugs and have some antitumor effects. However, they have rarely been tested in combination with other antitumor therapies, especially immunotherapy. Methods: We compared the progression-free survival (PFS) and overall survival (OS) of patients with advanced primary lung cancer (stage III or IV) receiving immunotherapy with H1 antihistamine diphenhydramine alone (n = 40) or in combination with H2 antihistamine cimetidine (n = 69) [experimental group] to those receiving immunotherapy alone (n = 75) or with a H2 antihistamine cimetidine (n = 27) [control group]. We used the inverse probability of treatment weights (IPTW) to balance the two groups. Kaplan Meier curves were used to compare OS and PFS between the two groups. Cox regression analyses were used to describe the association between patient characteristics and OS or PFS. Results: The experimental group comprised 109 patients, while the control group comprised 102. The median PFS (mPFS) was 12.7 months in the experimental group and 4.3 months in the control group (HR 0.46, 95% CI 0.35-0.63, P < 0.001). The median OS (mOS) was 32.8 months in the experimental group and 18.1 months in the control group (HR 0.63, 95% CI 0.44-0.91, P = 0.038). In the experimental group, patients treated with only H1 antihistamine had longer mPFS and mOS as compared with those who received H1 plus H2 antihistamines (mPFS: 18.0 months vs. 6.8 months, HR 1.40, 95% CI 0.26-0.63, P < 0.001; mOS: not reached vs. 26.6 months, HR 0.55, 95% CI 0.32-0.94, P = 0.030). In the control group, patients who received no antihistamine had longer mPFS and mOS compared to those who received only H2 antihistamines (mPFS: 5.8 months vs. 4.1 months, HR 0.44, 95% CI 0.29-0.67, P < 0.001; mOS: 25.5 vs. 16.9 months, HR 0.61, 95% CI 0.37-1.00, P = 0.049). After multivariate analyses, H1 antihistamine was the independent good prognostic factor for PFS and OS (PFS: HR 0.44, 95% CI 0.31-0.65, P < 0.001; OS: HR 0.62, 95% CI 0.39-0.99, P = 0.047). Conversely, H2 antihistamine was the independent poor prognostic factor for PFS and OS (PFS: HR 2.44, 95% CI 1.67-3.57, P < 0.001; OS: HR 2.38, 95% CI 1.49-3.70, P < 0.001). After IPTW, the rate of any grade of irAEs in the experimental group was 52.4%, while that of the control group was 69.2% ( P = 0.015), including 4.5% for irAEs grades ≥3 in the experimental group and 25.9% for irAEs grades ≥3 in the control group ( P = 0.003). Conclusions: Concomitant H1 antihistamines can not only improve immunotherapy efficacy but also reduce irAEs. Concomitant use of H2 antihistamines may shorten PFS and OS time.