For patients with nongerminal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL), the addition of ibrutinib to therapy based on rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was recently shown to improve outcomes for patients younger than 60 years of age, but not for patients age 60 or older. Study results were published in the Journal of Clinical Oncology.
In this phase 3 trial, patients were randomized to receive either ibrutinib plus R-CHOP (419 patients) or a placebo plus R-CHOP (419 patients). Event-free survival (EFS) was the primary endpoint, evaluated for both the intent-to-treat (TT) population and patients with activated B-cell (ABC) DLBCL. Overall survival (OS), progression-free survival (PFS), and safety were secondary endpoints. A preplanned subgroup analysis examined the influence of age.
The primary endpoint of EFS was not met for either the ITT or the ABC DLBCL groups. Overall, OS and PFS endpoints were also not met. However, responses differed by age groups.
For patients younger than 60 years, EFS was significantly better with ibrutinib added to R-CHOP (hazard ratio [HR], 0.579 in the ITT population; P =.0099). For this age group, addition of ibrutinib was also associated with improved OS (HR, 0.330 in the ITT population; P =.0013) and PFS (HR, 0.556 in the ITT population; P =.0075).
Patients aged 60 years and older trended toward poorer rates of EFS, OS, and PFS in the ibrutinib plus R-CHOP group. In the ITT population, HRs for this age group with ibrutinib were 1.228 for EFS (P =.2153), 1.440 for OS (P =.0739), and 1.200 for PFS (P =.2731).
For younger patients, the rates of serious adverse events were 35.7% with ibrutinib and 28.6% without ibrutinib. For older patients, these rates were 63.4% with ibrutinib and 38.2% without. Completion of 6 or more cycles of R-CHOP was lower for older patients receiving ibrutinib.
Although ibrutinib plus R-CHOP improved outcomes for younger patients with DLBCL, for older patients, this combination was associated with lower tolerability and nonsuperior outcomes.
Younes A, Sehn LH, Johnson P, et al. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma [published online March 22, 2019]. J Clin Oncol. doi:10.1200/jco.18.02403