TY - JOUR
T1 - Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia
AU - Burger, Jan A.
AU - Sivina, Mariela
AU - Jain, Nitin
AU - Kim, Ekaterina
AU - Kadia, Tapan
AU - Estrov, Zeev
AU - Nogueras-Gonzalez, Graciela M.
AU - Huang, Xuelin
AU - Jorgensen, Jeffrey
AU - Li, Jianling
AU - Cheng, Mei
AU - Clow, Fong
AU - Ohanian, Maro
AU - Andreeff, Michael
AU - Mathew, Thomas
AU - Thompson, Philip
AU - Kantarjian, Hagop
AU - O'Brien, Susan
AU - Wierda, William G.
AU - Ferrajoli, Alessandra
AU - Keating, Michael J.
N1 - Publisher Copyright:
© 2019 by The American Society of Hematology.
PY - 2019
Y1 - 2019
N2 - Ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, is an effective therapy for patients with chronic lymphocytic leukemia (CLL). To determine whether rituximab provides added benefit to ibrutinib, we conducted a randomized single-center trial of ibrutinib vs ibrutinib plus rituximab. Patients with CLL requiring therapy were randomized to receive 28-day cycles of once-daily ibrutinib 420 mg, either as a single agent (n = 104), or together with rituximab (375 mg/m2; n = 104), given weekly during cycle 1, then once per cycle until cycle 6. The primary end point was progression-free survival (PFS) in the intention-to-treat population. We enrolled 208 patients with CLL, 181 with relapsed CLL and 27 treatmentnaive patients with high-risk disease (17p deletion or TP53 mutation). After a median follow-up of 36 months, the Kaplan-Meier estimates of PFS were 86% (95% confidence interval [CI], 76.6-91.9) for patients receiving ibrutinib, and 86.9% (95% CI, 77.3-92.6) for patients receiving ibrutinib plus rituximab. Similarly, response rates were the same in both arms (overall response rate, 92%). However, time to normalization of peripheral blood lymphocyte counts and time to complete remission were shorter, and residual disease levels in the bone marrow were lower, in patients receiving ibrutinib plus rituximab. We conclude that the addition of rituximab to ibrutinib in relapsed and treatment-naive high-risk patients with CLL failed to show improvement in PFS. However, patients treated with ibrutinib plus rituximab reached their remissions faster and achieved significantly lower residual disease levels. Given these results, ibrutinib as single-agent therapy remains current standard-of-care treatment in CLL.
AB - Ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, is an effective therapy for patients with chronic lymphocytic leukemia (CLL). To determine whether rituximab provides added benefit to ibrutinib, we conducted a randomized single-center trial of ibrutinib vs ibrutinib plus rituximab. Patients with CLL requiring therapy were randomized to receive 28-day cycles of once-daily ibrutinib 420 mg, either as a single agent (n = 104), or together with rituximab (375 mg/m2; n = 104), given weekly during cycle 1, then once per cycle until cycle 6. The primary end point was progression-free survival (PFS) in the intention-to-treat population. We enrolled 208 patients with CLL, 181 with relapsed CLL and 27 treatmentnaive patients with high-risk disease (17p deletion or TP53 mutation). After a median follow-up of 36 months, the Kaplan-Meier estimates of PFS were 86% (95% confidence interval [CI], 76.6-91.9) for patients receiving ibrutinib, and 86.9% (95% CI, 77.3-92.6) for patients receiving ibrutinib plus rituximab. Similarly, response rates were the same in both arms (overall response rate, 92%). However, time to normalization of peripheral blood lymphocyte counts and time to complete remission were shorter, and residual disease levels in the bone marrow were lower, in patients receiving ibrutinib plus rituximab. We conclude that the addition of rituximab to ibrutinib in relapsed and treatment-naive high-risk patients with CLL failed to show improvement in PFS. However, patients treated with ibrutinib plus rituximab reached their remissions faster and achieved significantly lower residual disease levels. Given these results, ibrutinib as single-agent therapy remains current standard-of-care treatment in CLL.
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U2 - 10.1182/blood-2018-10-879429
DO - 10.1182/blood-2018-10-879429
M3 - Article
C2 - 30530801
AN - SCOPUS:85059002948
SN - 0006-4971
VL - 133
SP - 1011
EP - 1019
JO - Blood
JF - Blood
IS - 10
ER -