Ibrutinib and standard immunochemotherapy in younger, high‐risk patients with diffuse large B‐cell lymphoma: A phase II study of GLA

Summary

Younger patients with high‐risk diffuse large B‐cell lymphoma (DLBCL) frequently have unfavourable outcomes. We conducted a prospective phase II study evaluating ibrutinib plus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R‐CHOEP+I) in patients aged 18–60 years with DLBCL and age‐adjusted international prognostic index ≥2. Patients received ibrutinib (560 mg daily, d1‐112) combined with eight cycles of R‐CHOEP q2w. The primary end‐point was 2‐year progression‐free survival (PFS). Outcomes were compared exploratorily with those of patients with identical inclusion criteria treated with R‐CHOEP alone in the R‐MegaCHOEP phase III trial ( n  = 130). Forty patients started R‐CHOEP+I. Ibrutinib was administered for a median of 96 days, and 42% of patients completed treatment fully according to protocol. The overall response rate was 92%. Sixty‐eight per cent received all R‐CHOEP cycles compared with 88% in R‐MegaCHOEP; 22% vs. 49% of patients with bulky and/or extranodal disease underwent radiotherapy. With a median follow‐up of 31 months, 2‐year PFS was 83% (95% CI, 71–95) vs. 75% (95% CI, 67–82) after R‐CHOEP alone ( p  = 0.237). Exploratory cell‐of‐origin analyses suggested favourable outcomes in activated B‐cell‐type disease, but these findings remain descriptive. Grade ≥3 haematological adverse events were frequent, although no treatment‐related deaths occurred. In this prematurely closed phase II study, the addition of ibrutinib to R‐CHOEP showed encouraging activity. However, findings remain exploratory and hypothesis generating only.