Efficacy of Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma: A Combined Analysis of Three Phase III Randomized Controlled Trials
| Autor: | Ye Aung, Thura Win Htut, Fred Hardwicke, Sriman Swarup, Nicholas D'Cunha, Nimesh Adhikari, Kyaw Zin Thein, Pwint Phyu Hlaing, Lukman Tijani, Yin Mon Myat, Donald P. Quick, Anita Sultan, Myat Min Han, Upama Sharma |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
medicine.medical_specialty business.industry Immunology Lymphoproliferative disorders Cell Biology Hematology medicine.disease Ofatumumab Biochemistry Small cell lymphoma Lymphocytic lymphoma law.invention chemistry.chemical_compound Randomized controlled trial chemistry law Internal medicine Ibrutinib medicine Rituximab Refractory Chronic Lymphocytic Leukemia business medicine.drug |
| Zdroj: | Blood. 134:5479-5479 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Introduction: The B-cell receptor signaling pathway involves in the pathogenesis of chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/ SLL), the most common adult lymphoproliferative disorder in western countries. Ibrutinib, a novel Bruton's tyrosine kinase (BTK) inhibitor, has shown great efficacy in the treatment of hematological malignancies via inhibition of BTK, a kinase involved in cellular signaling downstream of the B-cell receptor. However, treatment becomes more challenging upon progression after initial treatment. We performed a combined analysis of currently available randomized controlled trials (RCTs) to evaluate the efficacy of ibrutinib in relapsed or refractory CLL/SLL. Methods: We systematically conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 2019. Phase III RCTs utilizing ibrutinib in patients with previously treated, relapsed or refractory CLL/SLL were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for progression-free survival (PFS) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q -statistic. Random effects model was applied. Results: Three phase III RCTs (HELIOS, RESONATE and Huang et al. studies) with a total of 1,129 patients with relapsed or refractory CLL/SLL were eligible. Studies compared ibrutinib vs ofatumumab, ibrutinib vs rituximab, and ibrutinib+ bendamustine+ rituximab vs bendamustine+ rituximab were included in the analysis. The randomization ratio was 2:1 in Huang et al. study and 1:1 in other studies. The I2 statistic for heterogeneity was 49, suggesting some heterogeneity among RCT. The pooled HR for PFS was statistically significant at 0.17 (95% CI: 0.12-0.22; P < 0.0001). The PFS benefit was observed in all Rai stages, either del11q or del17p status and bulky disease (≥ 5cm); Rai stage ≤ 2 cohort (HR, 0.14; 95% CI: 0.09- 0.22; P < 0.0001), Rai stage >2 cohort (HR, 0.26; 95% CI: 0.19- 0.36; P < 0.0001), del11q group (HR, 0.10; 95% CI: 0.06- 0.17; P < 0.0001), del17p group (HR, 0.24; 95% CI: 0.14- 0.39; P < 0.0001), and bulky disease cohort (HR, 0.19; 95% CI: 0.15- 0.25; P < 0.0001). Conclusions: Our study depicted that ibrutinib maintains activity in previously treated, relapsed or refractory CLL/SLL, across all Rai stages, in bulky disease and in del11q or del17p. Thus, the use of ibrutinib is likely beneficial to patients with relapsed or refractory CLL/SLL, regardless of disease stage, bulkiness or del11q/del 17p status. Disclosures No relevant conflicts of interest to declare. |
| Databáze: | OpenAIRE |
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