Combination Therapy: Ibrutinib, Rituximab, and R-CHOP in Non-Germinal Center B-Cell DLBCL

Ibrutinib has demonstrated efficacy in non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL). This double-blind phase III clinical trial assessed the effectiveness of ibrutinib and rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for the treatment of newly diagnosed non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL). The participants were randomly allocated in a 1:1 ratio to receive ibrutinib (560 mg per day administered orally) in combination with R-CHOP or placebo in combination with R-CHOP. The main objective of the study was to assess event-free survival (EFS) in both the intent-to-treat (ITT) population and the subgroup of patients with activated B-cell (ABC) DLBCL. Secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety measures.

About 838 patients were randomly allocated to receive ibrutinib in combination with R-CHOP (n = 419) or placebo in combination with R-CHOP (n = 419). The median age of the patients was 62.0 years. Among the patients who could be evaluated, 75.9% had ABC subtype disease. The baseline characteristics of the patients were evenly distributed. The combination of Ibrutinib and R-CHOP did not result in a significant improvement in Event-Free Survival (EFS) among the Intention-to-Treat (ITT) population (hazard ratio [HR], 0.934) or the Activated B-Cell (ABC) population (HR, 0.949). A premeditated examination revealed a notable correlation between the intervention and age. In patients aged less than 60 years, the combination of ibrutinib and R-CHOP demonstrated improvements in EFS (hazard ratio [HR] of 0.579), PFS (HR of 0.556), and OS (HR of 0.330). However, it was observed that there was a slight increase in the occurrence of serious adverse events (35.7% versus 28.6%) with this treatment. Nonetheless, the proportion of patients who received at least six cycles of R-CHOP was similar between the two treatment groups (92.9% versus 93.0%). In elderly patients aged 60 years or above, the combination of ibrutinib and R-CHOP treatment resulted in a deterioration of event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).

Additionally, there was an increase in serious adverse events (63.4% versus 38.2%) and a decrease in the proportion of patients who received at least six cycles of R-CHOP treatment (73.7% versus 88.8%). The study did not achieve statistical significance in meeting its primary outcome measure in the intention-to-treat (ITT) or as-treated (ABC) population. However, in patients aged younger than 60 years, the administration of ibrutinib in combination with R-CHOP resulted in improved Event-Free Survival (EFS), Progression-Free Survival (PFS), and Overall Survival (OS) outcomes while maintaining a manageable level of safety. In individuals aged 60 years or older, the combination of ibrutinib and R-CHOP treatment exhibited heightened toxicity, resulting in compromised administration of R-CHOP and unfavorable outcomes. Additional medical evaluation is indicated.

Source: https://pubmed.ncbi.nlm.nih.gov/30901302/

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT01855750

Younes A, Sehn LH, Johnson P, Zinzani PL, Hong X, Zhu J, Patti C, Belada D, Samoilova O, Suh C, Leppä S, Rai S, Turgut M, Jurczak W, Cheung MC, Gurion R, Yeh SP, Lopez-Hernandez A, Dührsen U, Thieblemont C, Chiattone CS, Balasubramanian S, Carey J, Liu G, Shreeve SM, Sun S, Zhuang SH, Vermeulen J, Staudt LM, Wilson W; PHOENIX investigators. 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. J Clin Oncol. 2019 May 20;37(15):1285-1295. doi: 10.1200/JCO.18.02403. Epub 2019 Mar 22. PMID: 30901302; PMCID: PMC6553835.