Association of proton pump inhibitor use with survival and adverse effects outcomes in patients with multiple myeloma: pooled analysis of three clinical trials.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 Jan 2024
05 Jan 2024
Historique:
received:
22
08
2023
accepted:
28
11
2023
medline:
6
1
2024
pubmed:
6
1
2024
entrez:
5
1
2024
Statut:
epublish
Résumé
Proton pump inhibitors (PPIs) are commonly used in cancer patients, but their impact on treatment outcomes in multiple myeloma (MM) patients remains unclear. This study investigated the association of PPI use with survival and adverse effects in MM patients across three randomized-control trials initiating daratumumab, lenalidomide, or bortezomib combination treatments. Cox proportional hazard analysis and logistic regression were employed to assess the associations with treatment outcomes, while adjusting for age, sex, weight, MM international staging system stage, ECOG-performance status, comorbidity count, and presence of gastrointestinal disorders. Pooled data involving 1804 patients revealed that 557 (32%) used PPIs at baseline. PPI use was independently associated with worse overall survival (adjusted HR [95% CI] 1.32 [1.08-1.62], P = 0.007) and grade ≥ 3 adverse events (adjusted OR [95% CI] 1.39 [1.03-1.88], P = 0.030). However, the association with progression-free survival did not reach statistical significance (adjusted HR [95% CI] 1.14 [0.97-1.33], P = 0.112). Findings were consistent across trials and treatment arms. PPI use was identified as a negative prognostic factor in MM patients, potentially enhancing clinical decisions regarding its use. Further research is needed to fully comprehend the impacts and safety of PPI use in MM patients.
Identifiants
pubmed: 38182614
doi: 10.1038/s41598-023-48640-1
pii: 10.1038/s41598-023-48640-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
591Subventions
Organisme : National Health and Medical Research Council Fellowship Grant
ID : APP2008119
Organisme : University of Sharjah Seed Grant
ID : 2301110380
Informations de copyright
© 2024. The Author(s).
Références
De Luca, F. et al. Monoclonal antibodies: The greatest resource to treat multiple myeloma. Int. J. Mol. Sci. 24, 3136 (2023).
doi: 10.3390/ijms24043136
pubmed: 36834545
pmcid: 9959320
Mian, A. et al. Incidence of second primary malignancies in patients with multiple myeloma receiving anti-CD38 monoclonal antibodies: A systematic review and meta-analysis. Leuk. Res. https://doi.org/10.1016/j.leukres.2023.107324 (2023).
doi: 10.1016/j.leukres.2023.107324
pubmed: 37285641
Bhatt, P., Kloock, C. & Comenzo, R. Relapsed/refractory multiple myeloma: A review of available therapies and clinical scenarios encountered in myeloma relapse. Curr. Oncol. 30, 2322–2347 (2023).
doi: 10.3390/curroncol30020179
pubmed: 36826140
pmcid: 9954856
Uchiyama, A. A. et al. Proton pump inhibitors and oncologic treatment efficacy: A practical review of the literature for oncologists. Curr. Oncol. 28, 783–799 (2021).
doi: 10.3390/curroncol28010076
pubmed: 33546228
pmcid: 7985775
Fessler, J., Matson, V. & Gajewski, T. F. Exploring the emerging role of the microbiome in cancer immunotherapy. J. Immunother. Cancer 7, 1–15 (2019).
doi: 10.1186/s40425-019-0574-4
Bavishi, C. & Dupont, H. Systematic review: The use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment. Pharmacol. Ther. 34, 1269–1281 (2011).
doi: 10.1111/j.1365-2036.2011.04874.x
pubmed: 21999643
Imhann, F. et al. Proton pump inhibitors affect the gut microbiome. Gut 65, 740–748 (2016).
doi: 10.1136/gutjnl-2015-310376
pubmed: 26657899
Meriggi, F. Controversial link between proton pump inhibitors and anticancer agents: Review of the literature. Tumori J. 108, 204–212 (2022).
doi: 10.1177/03008916211025091
Lee, J. E. et al. Concomitant use of proton pump inhibitors and palbociclib among patients with breast cancer. JAMA Netw. Open 6, e2324852. https://doi.org/10.1001/jamanetworkopen.2023.24852 (2023).
doi: 10.1001/jamanetworkopen.2023.24852
pubmed: 37477917
pmcid: 10362477
Husain, M. et al. Proton pump inhibitor use (PPI) in patients treated with immune checkpoint inhibitors (ICI) for advanced cancer: Survival and prior therapy. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.2633 (Wolters Kluwer Health, 2021).
Bridoux, M., Simon, N. & Turpin, A. Proton pump inhibitors and cancer: Current state of play. Front. Pharmacol. 13, 798272. https://doi.org/10.3389/fphar.2022.798272 (2022).
doi: 10.3389/fphar.2022.798272
pubmed: 35359844
pmcid: 8963837
Leitinger, E., Hui, L. & Grigg, A. Is there a role for proton pump inhibitor prophylaxis in haematology patients?. Intern. Med. J. 49, 694–701 (2019).
doi: 10.1111/imj.14241
pubmed: 30719802
Liu, C. et al. An up-to-date investigation into the correlation between proton pump inhibitor use and the clinical efficacy of immune checkpoint inhibitors in advanced solid cancers: A systematic review and meta-analysis. Front. Oncol. 12, 753234 (2022).
doi: 10.3389/fonc.2022.753234
pubmed: 35280736
pmcid: 8907621
Hopkins, A. M. et al. Efficacy of atezolizumab in patients with advanced NSCLC receiving concomitant antibiotic or proton pump inhibitor treatment: Pooled analysis of five randomized control trials. J. Thorac. Oncol. 17, 758–767 (2022).
doi: 10.1016/j.jtho.2022.02.003
pubmed: 35183773
Hopkins, A. M. et al. Efficacy of first-line atezolizumab combination therapy in patients with non-small cell lung cancer receiving proton pump inhibitors: Post hoc analysis of IMpower150. Br. J. Cancer 126, 42–47 (2022).
doi: 10.1038/s41416-021-01606-4
pubmed: 34711947
Facon, T. et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): Overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 22, 1582–1596 (2021).
doi: 10.1016/S1470-2045(21)00466-6
pubmed: 34655533
Dimopoulos, M. A. et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N. Engl. J. Med. 375, 1319–1331 (2016).
doi: 10.1056/NEJMoa1607751
pubmed: 27705267
Palumbo, A. et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N. Engl. J. Med. 375, 754–766 (2016).
doi: 10.1056/NEJMoa1606038
pubmed: 27557302
Hmisc: Harrell Miscellaneous (2022).
Vilmar, A. et al. Increased mortality in patients with hematologic malignancies treated with proton pump inhibitors: A nationwide cohort study. Leuk. Lymphoma https://doi.org/10.1080/10428194.2023.2216324 (2023).
doi: 10.1080/10428194.2023.2216324
pubmed: 37840282
Hopkins, A. M., Kichenadasse, G., Karapetis, C. S., Rowland, A. & Sorich, M. J. Concomitant proton pump inhibitor use and survival in urothelial carcinoma treated with Atezolizumab Proton Pump Inhibitors and Immunotherapies. Clin. Cancer Res. 26, 5487–5493 (2020).
doi: 10.1158/1078-0432.CCR-20-1876
pubmed: 32933995
Wang, X. et al. Proton pump inhibitors and survival in patients with colorectal cancer: A Swedish population-based cohort study. Br. J. Cancer 125, 893–900 (2021).
doi: 10.1038/s41416-021-01480-0
pubmed: 34253872
pmcid: 8438017
Wei, N., Zheng, B., Que, W., Zhang, J. & Liu, M. The association between proton pump inhibitor use and systemic anti-tumour therapy on survival outcomes in patients with advanced non-small cell lung cancer: A systematic review and meta-analysis. Br. J. Clin. Pharmacol. 88, 3052–3063 (2022).
doi: 10.1111/bcp.15276
pubmed: 35165922
Papagerakis, S. et al. Proton pump inhibitors and histamine 2 blockers are associated with improved overall survival in patients with head and neck squamous carcinoma. Cancer Prev. Res. 7, 1258–1269 (2014).
doi: 10.1158/1940-6207.CAPR-14-0002
Canitano, A., Iessi, E., Spugnini, E. P., Federici, C. & Fais, S. Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma. Cancer Lett. 376, 278–283 (2016).
doi: 10.1016/j.canlet.2016.04.015
pubmed: 27084522
Jackson, M. A. et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut 65, 749–756 (2016).
doi: 10.1136/gutjnl-2015-310861
pubmed: 26719299
D’Angelo, C. R., Sudakaran, S. & Callander, N. S. Clinical effects and applications of the gut microbiome in hematologic malignancies. Cancer 127, 679–687 (2021).
doi: 10.1002/cncr.33400
pubmed: 33369893
Jian, X. et al. Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria. Microbiome 8, 1–21 (2020).
doi: 10.1186/s40168-020-00854-5
Calcinotto, A. et al. Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. Nat. Commun. 9, 4832 (2018).
doi: 10.1038/s41467-018-07305-8
pubmed: 30510245
pmcid: 6277390
Giordan, Q., Salleron, J., Vallance, C., Moriana, C. & Clement-Duchene, C. Impact of antibiotics and proton pump inhibitors on efficacy and tolerance of anti-PD-1 immune checkpoint inhibitors. Front. Immunol. 12, 716317 (2021).
doi: 10.3389/fimmu.2021.716317
pubmed: 34777340
pmcid: 8578856
Galustian, C. et al. The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol. Immunother. 58, 1033–1045 (2009).
doi: 10.1007/s00262-008-0620-4
pubmed: 19009291
Gandhi, A. K. et al. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors I karos and A iolos via modulation of the E 3 ubiquitin ligase complex CRL 4 CRBN. Br. J. Haematol. 164, 811–821 (2014).
doi: 10.1111/bjh.12708
pubmed: 24328678
Saltarella, I. et al. Mechanisms of resistance to anti-CD38 daratumumab in multiple myeloma. Cells 9, 167 (2020).
doi: 10.3390/cells9010167
pubmed: 31936617
pmcid: 7017193
Diao, X. Antibiotics and proton pump inhibitors suppress the efficacy of immunotherapy against non-small cell lung cancer. Thorac. Cancer 11, 1763 (2020).
doi: 10.1111/1759-7714.13470
pubmed: 32374445
pmcid: 7327691
Alkim, H., Unal, S., Okur, H. & Imir, T. Omeprazole inhibits natural killer cell functions. Dig. Dis. Sci. 53, 347–351 (2008).
doi: 10.1007/s10620-007-9869-2
pubmed: 17597410
Numico, G., Fusco, V., Franco, P. & Roila, F. Proton pump inhibitors in cancer patients: how useful they are? A review of the most common indications for their use. Crit. Rev. Oncol. Hematol. 111, 144–151 (2017).
doi: 10.1016/j.critrevonc.2017.01.014
pubmed: 28259289
Kaczmarczyk, O. et al. Effect of long-term proton pump inhibitor therapy on complete blood count parameters and selected trace elements: a pilot study. Polskie Archiwum Medycyny Wewnętrznej= Polish Arch. Intern. Med. 130 (2020).
Lespessailles, E. & Toumi, H. Proton pump inhibitors and bone health: An update narrative review. Int. J. Mol. Sci. https://doi.org/10.3390/ijms231810733 (2022).
doi: 10.3390/ijms231810733
pubmed: 36142643
pmcid: 9504265
Binnetoğlu, E. et al. Pantoprazole-induced thrombocytopenia in patients with upper gastrointestinal bleeding. Platelets 26, 10–12 (2015).
doi: 10.3109/09537104.2014.880108
pubmed: 24512269
Gouraud, A., Vochelle, V., Descotes, J. & Vial, T. Proton pump inhibitor-induced neutropenia: Possible cross-reactivity between omeprazole and pantoprazole. Clin. Drug Investig. 30, 559–563 (2010).
doi: 10.2165/11537230-000000000-00000
pubmed: 20586518
Watson, T. D., Stark, J. E. & Vesta, K. S. Pantoprazole-LNDUCED thrombocytopenia. Ann. Pharmacother. 40, 758–761 (2006).
doi: 10.1345/aph.1G384
pubmed: 16569810