Τίτλος:
Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenström's Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
PURPOSE: The double-blind, randomized, placebo-controlled phase III iNNOVATE study showed sustained efficacy of ibrutinib-rituximab in Waldenström's macroglobulinemia (WM). Here, we present the final analysis from iNNOVATE. METHODS: Patients had confirmed symptomatic WM, either previously untreated or previously treated; patients with prior rituximab had at least a minor response to their last rituximab-based regimen. Patients were randomly assigned to once-daily ibrutinib 420 mg plus rituximab or placebo plus rituximab (n = 75 per arm). The primary end point was progression-free survival (PFS). Secondary end points included response rate, time to next treatment, hemoglobin improvement, overall survival, and safety. RESULTS: With a median follow-up of 50 (range, 0.5-63) months, median (95% CI) PFS was not reached (57.7 months to not evaluable) with ibrutinib-rituximab versus 20.3 months (13.0 to 27.6) with placebo-rituximab (hazard ratio, 0.250; P < .0001). PFS benefit was regardless of prior treatment status, MYD88 and CXCR4 mutation status, or key patient characteristics. Higher response rates (partial response or better) were observed with ibrutinib-rituximab (76% v 31% with placebo-rituximab; P < .0001) and were sustained over time. Median time to next treatment was not reached with ibrutinib-rituximab versus 18 months with placebo-rituximab. More patients receiving ibrutinib-rituximab versus placebo-rituximab had sustained hemoglobin improvement (77% v 43%; P < .0001). Median overall survival was not reached in either arm. Ibrutinib-rituximab maintained a manageable safety profile; the prevalence of grade ≥ 3 adverse events of clinical interest generally decreased over time. CONCLUSION: In the final analysis of iNNOVATE with a median follow-up of 50 months, ibrutinib-rituximab showed ongoing superiority across clinical outcomes in patients with WM regardless of MYD88 or CXCR4 mutation status, prior treatment, and key patient characteristics.
Συγγραφείς:
Buske, C.
Tedeschi, A.
Trotman, J.
García-Sanz, R.
MacDonald, D.
Leblond, V.
Mahe, B.
Herbaux, C.
Matous, J.V.
Tam, C.S.
Heffner, L.T.
Varettoni, M.
Palomba, M.L.
Shustik, C.
Kastritis, E.
Treon, S.P.
Ping, J.
Hauns, B.
Arango-Hisijara, I.
Dimopoulos, M.A.
Περιοδικό:
Journal of clinical oncology: official journal of the American Society of Clinical Oncology
Λέξεις-κλειδιά:
adenine; antineoplastic agent; chemokine receptor CXCR4; CXCR4 protein, human; ibrutinib; MYD88 protein, human; myeloid differentiation factor 88; piperidine derivative; rituximab; tumor marker, adult; aged; clinical trial; comparative study; controlled study; double blind procedure; female; genetics; human; male; middle aged; mortality; multicenter study; mutation; phase 3 clinical trial; randomized controlled trial; time factor; very elderly; Waldenstroem macroglobulinemia, Adenine; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Double-Blind Method; Female; Humans; Male; Middle Aged; Mutation; Myeloid Differentiation Factor 88; Piperidines; Progression-Free Survival; Receptors, CXCR4; Rituximab; Time Factors; Waldenstrom Macroglobulinemia
DOI:
10.1200/JCO.21.00838
