Addition of Ibrutinib to R-CHOP in Non–Germinal Center B-Cell DLBCL
In the phase III PHOENIX trial reported in the Journal of Clinical Oncology, Younes et al found that the addition of ibrutinib to R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) did not improve outcomes in patients with untreated non–germinal center B-cell diffuse large B-cell lymphoma (DLBCL). Benefits were observed in patients younger than 60 years old.
The double-blind trial included 838 patients from 28 countries. They were randomly assigned between October 2013 and November 2015 to receive oral ibrutinib at 560 mg/d plus R-CHOP (n = 419) or R-CHOP alone (n = 419).
The primary endpoint was event-free survival in the intent-to-treat population and in the subgroup of patients with activated B-cell DLBCL. Among 747 evaluable patients, 77.0% of patients in the ibrutinib plus R-CHOP group and 74.8% of those in the R-CHOP group had a confirmed activated B-cell subtype.
Event-Free Survival
The median follow-up was 34.8 months. Ibrutinib plus R-CHOP did not improve event-free survival vs R-CHOP in the intent-to-treat population (hazard ratio [HR] = 0.934, P = .5906) or the activated B-cell population (HR = 0.949, P = .7311). In the intent-to-treat population, no benefit was observed in progression-free survival (HR = 0.917, P = .5027) or overall survival (HR = 0.991, P = .9593).
Among the 342 patients in the intent-to-treat population aged < 60 years, ibrutinib plus R-CHOP improved event-free survival (HR = 0.579, P = .0099), progression-free survival (HR = 0.556, P = .0075), and overall survival (HR = 0.330, P = .0013), with similar benefits being observed in the activated B-cell subgroup aged < 60 years. In the intent-to-treat population aged < 60 years, there were more serious adverse events in the ibrutinib plus R-CHOP group (35.7% vs 28.6%); however, the proportion of patients receiving ≥ 6 cycles of R-CHOP was similar in the 2 groups (92.9% vs 93.0%).
In patients aged ≥ 60 years, ibrutinib plus R-CHOP was associated with worse event-free, progression-free, and overall survival; an increased incidence of serious adverse events (63.4% vs 38.2%); and a reduced proportion of patients receiving ≥ 6 cycles of R-CHOP (73.7% vs 88.8%).
The investigators concluded, “The study did not meet its primary endpoint in the [intent-to-treat] or [activated B-cell] population. However, in patients aged younger than 60 years, ibrutinib plus R-CHOP improved [event-free survival, progression-free survival, and overall survival] with manageable safety. In patients aged 60 years or older, ibrutinib plus R-CHOP was associated with increased toxicity, leading to compromised R-CHOP administration and worse outcomes. Further investigation is warranted.”
Anas Younes, MD, of the Lymphoma Service at Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Janssen Global Services. The study authors’ full disclosures can be found at jco.ascopubs.org.
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