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

Ariela Noy*, Sven de Vos, Morton Coleman, Peter Martin, Christopher R. Flowers, Catherine Thieblemont, Franck Morschhauser, Graham P. Collins, Shuo Ma, Shachar Peles, Stephen D. Smith, Jacqueline C. Barrientos, Elizabeth Chong, Shiquan Wu, Leo W.K. Cheung, Kevin Kwei, Bernhard Hauns, Israel Arango-Hisijara, Robert Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


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-kB 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.

Original languageEnglish (US)
Pages (from-to)5773-5784
Number of pages12
JournalBlood Advances
Issue number22
StatePublished - Nov 24 2020

ASJC Scopus subject areas

  • Hematology


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