Highlights
- •Study evaluating the effects of cationic amphiphilic antihistamines on immune checkpoint inhibitor therapy.
- •Cationic amphiphilic antihistamines were associated with survival benefits.
- •Effects not seen in patients who took cationic amphiphilic antihistamines before immune checkpoint inhibitor.
- •Benefits observed regardless of the generation of cationic amphiphilic antihistamines.
Abstract
Background
Cationic amphiphilic antihistamines have been shown to improve patient outcomes in
immunogenic tumours, but whether they can augment and improve response to immunotherapy
is unknown. We aim to evaluate the effect of cationic amphiphilic antihistamines in
patients receiving immune checkpoint inhibitors (ICIs).
Methods
We conducted a retrospective propensity score-matched cohort study at two tertiary
referral centres in Taiwan between January 2015 and December 2021. Patients who received
desloratadine, cyproheptadine, and ebastine were classified as cationic amphiphilic
antihistamine users. The primary outcome was overall survival, and the secondary outcomes
were progression-free survival and clinical benefit rate. Patients treated with cationic
amphiphilic antihistamines were matched to patients who received non-cationic amphiphilic
antihistamines based on variables including age, cancer type, stage, and history of
allergic diseases.
Results
A total of 734 ICI-treated patients were included. After matching, 68 cationic amphiphilic
antihistamine and non-cationic amphiphilic antihistamine users remained for analysis.
Compared with non-cationic amphiphilic antihistamine users, patients who received
cationic amphiphilic antihistamines had a significantly longer median overall survival
(24.8 versus 10.4 months; Log-rank, p = 0.018) and progression-free survival (10.6
versus 4.93 months; Log-rank, p = 0.004). The use of cationic amphiphilic antihistamines
was associated with an approximately 50% lower risk of all-cause mortality (HR, 0.55
[95% CI: 0.34–0.91]). Survival benefits were not seen in patients who received cationic
amphiphilic antihistamines before immune checkpoint blockade. These survival benefits
were observed regardless of the generation of cationic amphiphilic antihistamines.
Conclusion
The use of cationic amphiphilic antihistamines was associated with improved survival
among patients treated with immunotherapy.
Keywords
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References
- Cancer immunotherapy using checkpoint blockade.Science. Mar 23 2018; 359: 1350-1355https://doi.org/10.1126/science.aar4060
- Combining immune checkpoint inhibitors with chemotherapy in advanced solid tumours: a review.Eur J Cancer. Oct 13 2021; 158: 47-62https://doi.org/10.1016/j.ejca.2021.09.013
- Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs.JAMA Netw Open. May 3 2019; 2e192535https://doi.org/10.1001/jamanetworkopen.2019.2535
- Current strategies for intratumoural immunotherapy – beyond immune checkpoint inhibition.Eur J Cancer. Nov 2021; 157: 493-510https://doi.org/10.1016/j.ejca.2021.08.004
- Overcoming cancer therapeutic bottleneck by drug repurposing.Signal Transduct Target Ther. 2020; 5 (2020/07/02): 113https://doi.org/10.1038/s41392-020-00213-8
- Integrated analysis of concomitant medications and oncological outcomes from PD-1/PD-L1 checkpoint inhibitors in clinical practice.J Immunother Cancer. Nov 2020; 8https://doi.org/10.1136/jitc-2020-001361
- Renin-angiotensin-aldosterone system inhibitors and survival in patients with hypertension treated with immune checkpoint inhibitors.Eur J Cancer. Mar 2022; 163: 108-118https://doi.org/10.1016/j.ejca.2021.12.024
- Effect of concomitant medications with immune-modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index.Eur J Cancer. Jan 2021; 142: 18-28https://doi.org/10.1016/j.ejca.2020.09.033
- The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1.Cancer Cell. Jan 10 2022; 40: 36-52.e9https://doi.org/10.1016/j.ccell.2021.11.002
- Repurposing cationic amphiphilic antihistamines for cancer treatment.EBioMedicine. Jul 2016; 9: 130-139https://doi.org/10.1016/j.ebiom.2016.06.013
- Baseline co-medications may alter the anti-tumoural effect of checkpoint inhibitors as well as the risk of immune-related adverse events.Eur J Cancer. Nov 2021; 157: 474-484https://doi.org/10.1016/j.ejca.2021.08.036
- Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase.Cancer Cell. Sep 9 2013; 24: 379-393https://doi.org/10.1016/j.ccr.2013.08.003
- Cell death induced by cationic amphiphilic drugs depends on lysosomal Ca(2+) release and cyclic AMP.Mol Cancer Ther. Sep 2019; 18: 1602-1614https://doi.org/10.1158/1535-7163.Mct-18-1406
- Antihistamines and ovarian cancer survival: nationwide cohort study and in vitro cell viability assay.J Natl Cancer Inst. Sep 1 2020; 112: 964-967https://doi.org/10.1093/jnci/djz217
- Improved survival in several cancers with use of H(1)-antihistamines desloratadine and loratadine.Transl Oncol. Apr 2021; 14101029https://doi.org/10.1016/j.tranon.2021.101029
- Generating real-world tumor burden endpoints from electronic health record data: comparison of RECIST, radiology-anchored, and clinician-anchored approaches for abstracting real-world progression in non-small cell lung cancer.Adv Ther. Aug 2019; 36: 2122-2136https://doi.org/10.1007/s12325-019-00970-1
- An exploratory analysis of real-world end points for assessing outcomes among immunotherapy-treated patients with advanced non-small-cell lung cancer.JCO Clin Cancer Inform. Jul 2019; 3: 1-15https://doi.org/10.1200/cci.18.00155
- Variable selection for propensity score models.Am J Epidemiol. Jun 15 2006; 163: 1149-1156https://doi.org/10.1093/aje/kwj149
- A comparison of 12 algorithms for matching on the propensity score.Stat Med. Mar 15 2014; 33: 1057-1069https://doi.org/10.1002/sim.6004
- Nivolumab in resected and unresectable metastatic melanoma: characteristics of immune-related adverse events and association with outcomes.Clin Cancer Res. Feb 15 2016; 22: 886-894https://doi.org/10.1158/1078-0432.Ccr-15-1136
- Association of cutaneous immune-related adverse events with increased survival in patients treated with anti-programmed cell death 1 and anti-programmed cell death ligand 1 therapy.JAMA Dermatol. Feb 1 2022; 158: 189-193https://doi.org/10.1001/jamadermatol.2021.5476
- Risk of cancer in patients with medically diagnosed hay fever or allergic rhinitis.Int J Cancer. Nov 15 2014; 135: 2397-2403https://doi.org/10.1002/ijc.28873
- PD-L1 degradation pathway and immunotherapy for cancer.Cell Death Dis. Nov 6 2020; 11: 955https://doi.org/10.1038/s41419-020-03140-2
- Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti-PD-L1).Proc Natl Acad Sci U S A. Oct 23 2018; 115: E10119-E10126https://doi.org/10.1073/pnas.1802166115
- Statin safety and associated adverse events: a scientific statement from the american heart association.Arterioscler Thromb Vasc Biol. Feb 2019; 39: e38-e81https://doi.org/10.1161/atv.0000000000000073
- Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension.Cochrane Database Syst Rev. Aug 22 2014; 2014Cd009096https://doi.org/10.1002/14651858.CD009096.pub2
- Safety of antihistamines in children.Drug Saf. 2001; 24: 119-147https://doi.org/10.2165/00002018-200124020-00003
- Safety of second generation antihistamines.Allergy Asthma Proc. Jan-Feb 2000; 21: 15-20https://doi.org/10.2500/108854100778249033
- Antihistamines for the common cold.Cochrane Database Syst Rev. Nov 29 2015; Cd009345https://doi.org/10.1002/14651858.CD009345.pub2
- Trends in prescription medication use among children and adolescents-United States, 1999-2014.JAMA. May 15 2018; 319: 2009-2020https://doi.org/10.1001/jama.2018.5690
- H1-Antihistamines: more relevant than ever in the treatment of allergic disorders.J Allergy Clin Immunol. Oct 2003; 112: S42-S52https://doi.org/10.1016/s0091-6749(03)01876-1
Article info
Publication history
Published online: August 11, 2022
Accepted:
July 7,
2022
Received in revised form:
June 27,
2022
Received:
April 29,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
