Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis

被引:80
作者
Noy, Ariela [1 ,2 ]
de Vos, Sven [3 ]
Coleman, Morton [2 ]
Martin, Peter [2 ]
Flowers, Christopher R. [4 ]
Thieblemont, Catherine [5 ]
Morschhauser, Franck [6 ]
Collins, Graham P. [7 ]
Shuo, Ma [8 ]
Peles, Shachar [9 ]
Smith, Stephen D. [10 ]
Barrientos, Jacqueline C. [11 ]
Chong, Elizabeth [12 ]
Wu, Shiquan [12 ]
Cheung, Leo W-K [12 ]
Kwei, Kevin [12 ]
Hauns, Bernhard [12 ]
Arango-Hisijara, Israel [12 ]
Chen, Robert [13 ]
机构
[1] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA
[2] Weill Cornell Med Coll, New York, NY USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA
[4] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA
[5] Hop St Louis, Paris, France
[6] Ctr Hosp Reg Univ Lille, Hop Claude Huriez, Lille, France
[7] Churchill Hosp, Oxford Canc & Haematol Ctr, Oxford, England
[8] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
[9] Florida Canc Specialists, Atlantis, FL USA
[10] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA
[11] Northwell Hlth Canc Inst, Div Med Oncol & Hematol, New Hyde Pk, NY USA
[12] Pharmacycl LLC, Sunnyvale, CA USA
[13] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA
关键词
BRUTON TYROSINE KINASE; B-CELL LYMPHOMA; SINGLE-AGENT IBRUTINIB; RITUXIMAB; SURVIVAL; PCI-32765; CHEMOTHERAPY; INHIBITION; MIGRATION; GENETICS;
D O I
10.1182/bloodadvances.2020003121
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-kappa B 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.
引用
收藏
页码:5773 / 5784
页数:12
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