Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis
| Autor: | Shiquan Wu, Shuo Ma, Shachar Peles, Israel Arango-Hisijara, Bernhard Hauns, Kevin A. Kwei, Franck Morschhauser, Elizabeth Chong, Morton Coleman, Graham P. Collins, Sven de Vos, Jacqueline C. Barrientos, Stephen D. Smith, Robert T. Chen, Peter Martin, Catherine Thieblemont, Christopher R. Flowers, Leo W.-K. Cheung, Ariela Noy |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Anemia Gene mutation Gastroenterology chemistry.chemical_compound Refractory Piperidines Chemoimmunotherapy Internal medicine medicine Humans business.industry Adenine Hematology Lymphoma B-Cell Marginal Zone medicine.disease Confidence interval Lymphoma chemistry Ibrutinib Rituximab Neoplasm Recurrence Local business Biomarkers medicine.drug Follow-Up Studies |
| Zdroj: | Blood advances. 4(22) |
| ISSN: | 2473-9537 |
| Popis: | Advanced marginal zone lymphoma (MZL) is an incurable B-cell malignancy dependent on B-cell receptor signaling. The phase 2 PCYC-1121 study demonstrated the safety and efficacy of single-agent ibrutinib 560 mg/d in 63 patients with relapsed/refractory MZL treated with prior rituximab (RTX) or rituximab-based chemoimmunotherapy (RTX-CIT). We report the final analysis of PCYC-1121 with median follow-up of 33.1 months (range: 1.4-44.6). Overall response rate (ORR) was 58%; median duration of response (DOR) was 27.6 months (95% confidence interval [CI]: 12.1 to not estimable [NE]); median progression-free survival (PFS) was 15.7 months (95% CI: 12.2-30.4); and median overall survival (OS) was not reached (95% CI: NE to NE). Patients with prior RTX treatment had better outcomes (ORR: 81%; median DOR: not reached [95% CI: 12.2 to NE]; median PFS: 30.4 months [95% CI: 22.1 to NE]; median OS: not reached [95% CI: 30.3 to NE]) vs those with prior RTX-CIT treatment (ORR: 51%; DOR: 12.4 months [95% CI: 2.8 to NE]; PFS: 13.8 months [95% CI: 8.3-22.5]; OS: not reached [95% CI: NE to NE]). ORRs were 63%, 47%, and 62% for extranodal, nodal, and splenic subtypes, respectively. With up to 45 months of ibrutinib treatment, the safety profile remained consistent with prior reports. The most common grade ≥3 event was anemia (16%). Exploratory biomarker analysis showed NF-κB pathway gene mutations correlated with outcomes. Final analysis of PCYC-1121 demonstrated long-term safety and efficacy of ibrutinib in patients with relapsed/refractory MZL, regardless of prior treatment or MZL subtype. This trial was registered at www.clinicaltrials.gov as #NCT01980628. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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