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

doi:10.1182/bloodadvances.2020003121

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

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	5773-5784
Number of pages	12
Journal	Blood Advances
Volume	4
Issue number	22
DOIs	https://doi.org/10.1182/bloodadvances.2020003121
State	Published - Nov 24 2020

Funding

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.

ASJC Scopus subject areas

Hematology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1182/bloodadvances.2020003121

Cite this

Noy, A., de Vos, S., Coleman, M., Martin, P., Flowers, C. R., Thieblemont, C., Morschhauser, F., Collins, G. P., Ma, S., Peles, S., Smith, S. D., Barrientos, J. C., Chong, E., Wu, S., Cheung, L. W. K., Kwei, K., Hauns, B., Arango-Hisijara, I., & Chen, R. (2020). Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis. Blood Advances, 4(22), 5773-5784. https://doi.org/10.1182/bloodadvances.2020003121

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

abstract = "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.",

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

note = "Publisher Copyright: {\textcopyright} 2020 by The American Society of Hematology",

year = "2020",

month = nov,

day = "24",

doi = "10.1182/bloodadvances.2020003121",

language = "English (US)",

volume = "4",

pages = "5773--5784",

journal = "Blood Advances",

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publisher = "American Society of Hematology",

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Noy, A, de Vos, S, Coleman, M, Martin, P, Flowers, CR, Thieblemont, C, Morschhauser, F, Collins, GP, Ma, S, Peles, S, Smith, SD, Barrientos, JC, Chong, E, Wu, S, Cheung, LWK, Kwei, K, Hauns, B, Arango-Hisijara, I & Chen, R 2020, 'Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis', Blood Advances, vol. 4, no. 22, pp. 5773-5784. https://doi.org/10.1182/bloodadvances.2020003121

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

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

Abstract

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UN SDGs

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