TY - JOUR
T1 - Safety and efficacy of ibrutinib in combination with rituximab and lenalidomide in previously untreated follicular and marginal zone lymphoma
T2 - An open label, phase 2 study
AU - Gordon, Max J.
AU - Feng, Lei
AU - Strati, Paolo
AU - Lee, Hun Ju
AU - Hagemeister, Fredrick B.
AU - Westin, Jason R.
AU - Samaniego, Felipe
AU - Marques-Piubelli, Mario L.
AU - Vega Vazquez, Francisco
AU - Parra Cuentas, Edwin R.
AU - Solis-Soto, Luisa M.
AU - Ma, Wencai
AU - Wang, Jing
AU - Claret, Linda
AU - Averill, Barbara
AU - Ibanez, Karina
AU - Fayad, Luis E.
AU - Flowers, Christopher R.
AU - Green, Michael R.
AU - Davis, R. Eric
AU - Neelapu, Sattva S.
AU - Fowler, Nathan H.
AU - Nastoupil, Loretta J.
N1 - Publisher Copyright:
© 2023 American Cancer Society.
PY - 2024/3/15
Y1 - 2024/3/15
N2 - Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity—rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study. Methods: The authors conducted an open-label, phase 2 clinical trial of IRR for previously untreated FL and MZL. The primary end point was progression-free survival (PFS) at 24 months. Results: This study included 48 participants with previously untreated FL grade 1–3a (N = 38), or MZL (N = 10). Participants received 12, 28-day cycles of lenalidomide (15 mg, days 1–21 cycle 1; 20 mg, cycles 2–12), rituximab (375 mg/m2 weekly in cycle 1; day 1 cycles 2-12), and ibrutinib 560 mg daily. With a median follow-up of 65.3 months, the estimated PFS at 24 months was 78.8% (95% confidence interval [CI], 68.0%–91.4%) and 60-month PFS was 59.7% (95% CI, 46.6%–76.4%). One death occurred unrelated to disease progression. Grade 3–4 adverse events were observed in 64.6%, including 50% with grade 3–4 rash. Conclusions: IRR is highly active as frontline therapy for FL and MZL. Compared to historical results with lenalidomide and rituximab, PFS is similar with higher grade 3–4 toxicity, particularly rash. The study was registered with ClinicalTrials.gov (NCT02532257).
AB - Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity—rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study. Methods: The authors conducted an open-label, phase 2 clinical trial of IRR for previously untreated FL and MZL. The primary end point was progression-free survival (PFS) at 24 months. Results: This study included 48 participants with previously untreated FL grade 1–3a (N = 38), or MZL (N = 10). Participants received 12, 28-day cycles of lenalidomide (15 mg, days 1–21 cycle 1; 20 mg, cycles 2–12), rituximab (375 mg/m2 weekly in cycle 1; day 1 cycles 2-12), and ibrutinib 560 mg daily. With a median follow-up of 65.3 months, the estimated PFS at 24 months was 78.8% (95% confidence interval [CI], 68.0%–91.4%) and 60-month PFS was 59.7% (95% CI, 46.6%–76.4%). One death occurred unrelated to disease progression. Grade 3–4 adverse events were observed in 64.6%, including 50% with grade 3–4 rash. Conclusions: IRR is highly active as frontline therapy for FL and MZL. Compared to historical results with lenalidomide and rituximab, PFS is similar with higher grade 3–4 toxicity, particularly rash. The study was registered with ClinicalTrials.gov (NCT02532257).
KW - indolent lymphoma
KW - non-Hodgkin lymphoma (NHL)
KW - targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85177181553&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85177181553&partnerID=8YFLogxK
U2 - 10.1002/cncr.35114
DO - 10.1002/cncr.35114
M3 - Article
C2 - 37985359
AN - SCOPUS:85177181553
SN - 0008-543X
VL - 130
SP - 876
EP - 885
JO - Cancer
JF - Cancer
IS - 6
ER -