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:
Conflict-of-interest disclosure: A.N. reports employment with Memorial Sloan Kettering Cancer Center; has received honoraria from Janssen, Medscape, Prime Oncology, and Pharmacyclics LLC, an AbbVie Company; has a consulting role with MorphoSys and Janssen; has received research funding from Rafael and Pharmacy-clics LLC, an AbbVie Company; reports patent pending at Rafael; and has received travel expenses from Janssen and Pharmacyclics LLC, an AbbVie Company. S.d.V. has a consulting role with Bayer and Verastem. M.C. has stock ownership in Immunomedics; a consulting role with Pharmacyclics LLC, an AbbVie Company; has received research funding from AbbVie, Celgene, Genentech, BeiGene, and Pharmacyclics LLC, an AbbVie Company; and has received speaker fees from Celgene, Janssen, and Gilead. P.M. has consulting roles with AstraZeneca, Bayer, BeiGene, Cellectar, Celgene, I-MAB, Janssen, Karyopharm, Kite, MorphoSys, Sandoz, and TeneoBio; has received research funding from Karyopharm; and has received travel expenses from Janssen, MorphoSys and Bayer. C.R.F. has consulting roles with AbbVie, Spectrum, Celgene, Denovo Biopharma, OptumRx, Karyopharm, Pharmacyclics LLC, an AbbVie Company, Janssen, Gilead, and Bayer; has received research funding from AbbVie, Acerta, Celgene, Gilead, Genentech/Roche, Janssen, Millennium/Takeda, Pharmacyclics LLC, an AbbVie Company, and TG Therapeutics; and has received travel expenses from Genentech/ Roche. C.T. has received honoraria from Gilead and Novartis; has consulting roles with Roche, Janssen, Celgene, Gilead, Kite, Novartis, Bayer, and Cellectis; has received research funding from Roche and Hospira; and has received travel expenses from Novartis, Roche, Janssen, Celgene, Novartis, and Cellectis. F.M. has received honoraria from Celgene, Roche, Bristol-Myers Squibb, and Gilead; and has consulting roles with Celgene, Roche, Epizyme, Gilead, and Bayer. G.P.C. has received honoraria from Takeda, Roche, Gilead, Bristol Myers Squibb, Merck, Celleron, ADC Therapeutics, Novartis, and Pfizer; has consulting roles with Takeda, Roche, Gilead, Bristol Myers Squibb, Merck, Celleron, and ADC Therapeutics; has received research funding from Bristol Myers Squibb, Celleron, Merck, Amgen, and Celgene; has received speaker fees from Takeda, Roche, Gilead, Novartis, and Bristol Myers Squibb; and has received travel expenses from Takeda and Roche; and has received support from NIHR Oxford
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
VL - 4
SP - 5773
EP - 5784
JO - Blood advances
JF - Blood advances
SN - 2473-9529
IS - 22
ER -