TY - JOUR
T1 - Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma
T2 - long-term follow-up and biomarker analysis
AU - Noy, Ariela
AU - de Vos, Sven
AU - Coleman, Morton
AU - Martin, Peter
AU - Flowers, Christopher R.
AU - Thieblemont, Catherine
AU - Morschhauser, Franck
AU - Collins, Graham P.
AU - Ma, Shuo
AU - Peles, Shachar
AU - Smith, Stephen D.
AU - Barrientos, Jacqueline C.
AU - Chong, Elizabeth
AU - Wu, Shiquan
AU - Cheung, Leo W.K.
AU - Kwei, Kevin
AU - Hauns, Bernhard
AU - Arango-Hisijara, Israel
AU - Chen, Robert
N1 - Funding Information:
This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Medical writing support was provided by Melanie Sweet-love and funded by Pharmacyclics LLC, an AbbVie Company. C.R.F. is a CPRIT Scholar supported by a Cancer Prevention and Research in Texas grant to The University of Texas MD Anderson Cancer Center.
Publisher Copyright:
© 2020 by The American Society of Hematology
PY - 2020/11/24
Y1 - 2020/11/24
N2 - 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.
AB - 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.
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U2 - 10.1182/bloodadvances.2020003121
DO - 10.1182/bloodadvances.2020003121
M3 - Article
C2 - 33227125
AN - SCOPUS:85097321336
SN - 2473-9529
VL - 4
SP - 5773
EP - 5784
JO - Blood advances
JF - Blood advances
IS - 22
ER -