Phase Ib Study Shows Activity of Ibrutinib Plus R-CHOP in First-Line Treatment of CD20-Positive B-Cell Non-Hodgkin Lymphoma


Key Points

  • An ibrutinib dose of 560 mg/d in combination with R-CHOP was selected for phase II evaluation.
  • Response was observed in all patients with diffuse large B-cell lymphoma who received 560 mg/d.

The oral Bruton's tyrosine kinase inhibitor ibrutinib (Imbruvica) has shown activity in relapsed and refractory B-cell malignancies. In a phase Ib trial reported in The Lancet Oncology, Younes et al identified no maximum tolerated dose of ibrutinib when combined with R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) in first-line treatment in patients with CD20-positive B-cell non-Hodgkin lymphoma. A dose of 560 mg/d is being moved forward to phase II evaluation. Response was observed in almost all patients across the ibrutinib doses tested.

In the study, conducted at six centers in the United States and France, 33 patients with diffuse large B-cell lymphoma, mantle cell lymphoma, or follicular lymphoma received ibrutinib 280, 420, or 560 mg/d combined with standard R-CHOP.

No Maximum Tolerated Dose

The maximum tolerated dose was not reached. The most common grade ≥ 3 adverse events were neutropenia (73%), thrombocytopenia (21%), febrile neutropenia (18%), and anemia (18%). The most frequent serious adverse events were febrile neutropenia (18%) and hypotension (6%). There was no evidence of an effect of R-CHOP on ibrutinib pharmacokinetics or of an effect of ibrutinib on vincristine pharmacokinetics.


Response was observed in 30 (94%) of 32 patients who received at least one dose of combination treatment, including 18 (100%) of 18 patients with diffuse large B-cell lymphoma who received the recommended phase II ibrutinib dose of 560 mg/d. Among patients with subtyped disease who received 560 mg/d, complete response was observed in five of seven patients with germinal center B-cell–like subtype and each of two with non–germinal center B-cell–like subtype.

The investigators concluded: “Ibrutinib is well tolerated when added to R-CHOP, and could improve responses in patients with B-cell non-Hodgkin lymphoma, but our findings need confirmation in a phase 3 trial.”

Anas Younes, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for The Lancet Oncology article.

The study was funded by Janssen. For full disclosures of the study authors, visit

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