Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials
Abstract: Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) have seen significant treatment advancements with the emergence of Bruton tyrosine kinase inhibitors like ibrutinib. Statin use has been linked to reduced mortality in several cancers, including CLL. Howe...
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Elsevier
2025-07-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925002435 |
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| author | Ahmad Y. Abuhelwa Sara A. Almansour Jennifer R. Brown Humaid O. Al-Shamsi Ziad Abuhelwa Zelal Kharaba Yasser Bustanji Mohammad H. Semreen Salma Ali Ahmad Alhuraiji Ross A. McKinnon Michael J. Sorich Karem H. Alzoubi Ashley M. Hopkins |
| author_facet | Ahmad Y. Abuhelwa Sara A. Almansour Jennifer R. Brown Humaid O. Al-Shamsi Ziad Abuhelwa Zelal Kharaba Yasser Bustanji Mohammad H. Semreen Salma Ali Ahmad Alhuraiji Ross A. McKinnon Michael J. Sorich Karem H. Alzoubi Ashley M. Hopkins |
| author_sort | Ahmad Y. Abuhelwa |
| collection | DOAJ |
| description | Abstract: Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) have seen significant treatment advancements with the emergence of Bruton tyrosine kinase inhibitors like ibrutinib. Statin use has been linked to reduced mortality in several cancers, including CLL. However, their concomitant use with targeted therapies such as ibrutinib remains unexplored. This study investigates the association of statin use with survival and adverse event outcomes in patients with CLL/SLL initiating contemporary treatment regimens, including ibrutinib. Individual participant data from 4 randomized trials—RESONATE, RESONATE-2, iLLUMINATE, and HELIOS—were used. Associations between baseline statin use and treatment outcomes were examined using Cox proportional hazards models for overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CCS), and logistic regression models for grade ≥3 adverse effects. Analyses were adjusted for age, sex, weight, Eastern Cooperative Oncology Group performance status, disease diagnosis, bulky disease (≥5 cm), time since diagnosis, comorbidity count, and the use of beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and diuretics. Of 1467 patients, 424 (29%) were using statins. Statin use was significantly associated with improved OS (adjusted hazard ratio [aHR] 0.62 [95% CI, 0.48‑0.79], P < 0.001), PFS (aHR 0.74 [95% CI, 0.62-0.89], P = 0.001), and CCS (aHR 0.39 [95% CI, 0.22–0.70], P = 0.001). Findings were consistent across ibrutinib vs nonibrutinib treatment arms and CLL vs SLL diagnosis. No significant association with grade ≥3 adverse effects was observed. Statin use was identified as an independent positive prognostic factor in patients with CLL/SLL, irrespective of the treatment employed. Further research is needed to validate these results and explore the underlying impacts of statins in CLL/SLL. These trials were registered at www.ClinicalTrials.gov as #NCT01578707, #NCT01722487, #NCT02264574, and #NCT01611090. |
| format | Article |
| id | doaj-art-b464eaafb8084275a4e7aafa24f62ede |
| institution | DOAJ |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-b464eaafb8084275a4e7aafa24f62ede2025-08-20T03:12:56ZengElsevierBlood Advances2473-95292025-07-019143566357510.1182/bloodadvances.2024015287Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trialsAhmad Y. Abuhelwa0Sara A. Almansour1Jennifer R. Brown2Humaid O. Al-Shamsi3Ziad Abuhelwa4Zelal Kharaba5Yasser Bustanji6Mohammad H. Semreen7Salma Ali8Ahmad Alhuraiji9Ross A. McKinnon10Michael J. Sorich11Karem H. Alzoubi12Ashley M. Hopkins13Department of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, United Arab Emirates; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Correspondence: Ahmad Y. Abuhelwa, Department of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, United Arab Emirates;Department of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, United Arab EmiratesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MADepartment of Oncology, Burjeel Cancer Institute, Burjeel Medical City, Abu Dhabi, United Arab Emirates; Emirates Oncology Society, Dubai, United Arab Emirates; College of Medicine, Ras Al Khaimah Medical and Health Sciences, Ras Al Khaimah, United Arab Emirates; Gulf Cancer Society, Alsafa, KuwaitDepartment of Hematology and Medical Oncology, University of South Florida/H. Lee Moffitt Cancer Center and Research Institute, Tampa, FLDepartment of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, United Arab Emirates; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab EmiratesDepartment of Clinical Sciences, University of Sharjah, Sharjah, United Arab Emirates; Department of Biopharmaceutics and Clinical Pharmacy, the University of Jordan, Amman, JordanResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Department of Medicinal Chemistry, University of Sharjah, Sharjah, United Arab EmiratesDepartment of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, United Arab Emirates; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab EmiratesDepartment of Haematology, Kuwait Cancer Control Center, Kuwait City, KuwaitCollege of Medicine and Public Health, Flinders University, Bedford Park, SA, AustraliaCollege of Medicine and Public Health, Flinders University, Bedford Park, SA, AustraliaDepartment of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, United Arab Emirates; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanCollege of Medicine and Public Health, Flinders University, Bedford Park, SA, AustraliaAbstract: Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) have seen significant treatment advancements with the emergence of Bruton tyrosine kinase inhibitors like ibrutinib. Statin use has been linked to reduced mortality in several cancers, including CLL. However, their concomitant use with targeted therapies such as ibrutinib remains unexplored. This study investigates the association of statin use with survival and adverse event outcomes in patients with CLL/SLL initiating contemporary treatment regimens, including ibrutinib. Individual participant data from 4 randomized trials—RESONATE, RESONATE-2, iLLUMINATE, and HELIOS—were used. Associations between baseline statin use and treatment outcomes were examined using Cox proportional hazards models for overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CCS), and logistic regression models for grade ≥3 adverse effects. Analyses were adjusted for age, sex, weight, Eastern Cooperative Oncology Group performance status, disease diagnosis, bulky disease (≥5 cm), time since diagnosis, comorbidity count, and the use of beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and diuretics. Of 1467 patients, 424 (29%) were using statins. Statin use was significantly associated with improved OS (adjusted hazard ratio [aHR] 0.62 [95% CI, 0.48‑0.79], P < 0.001), PFS (aHR 0.74 [95% CI, 0.62-0.89], P = 0.001), and CCS (aHR 0.39 [95% CI, 0.22–0.70], P = 0.001). Findings were consistent across ibrutinib vs nonibrutinib treatment arms and CLL vs SLL diagnosis. No significant association with grade ≥3 adverse effects was observed. Statin use was identified as an independent positive prognostic factor in patients with CLL/SLL, irrespective of the treatment employed. Further research is needed to validate these results and explore the underlying impacts of statins in CLL/SLL. These trials were registered at www.ClinicalTrials.gov as #NCT01578707, #NCT01722487, #NCT02264574, and #NCT01611090.http://www.sciencedirect.com/science/article/pii/S2473952925002435 |
| spellingShingle | Ahmad Y. Abuhelwa Sara A. Almansour Jennifer R. Brown Humaid O. Al-Shamsi Ziad Abuhelwa Zelal Kharaba Yasser Bustanji Mohammad H. Semreen Salma Ali Ahmad Alhuraiji Ross A. McKinnon Michael J. Sorich Karem H. Alzoubi Ashley M. Hopkins Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials Blood Advances |
| title | Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials |
| title_full | Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials |
| title_fullStr | Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials |
| title_full_unstemmed | Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials |
| title_short | Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials |
| title_sort | statin use and survival in cll sll treated with ibrutinib pooled analysis of 4 randomized controlled trials |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925002435 |
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