Patients With BCL2/MYC High-Expressing Non-GCB DLBCL May Be Preferentially Responsive to BTK Inhibitor Ibrutinib Plus R-CHOP Regimen

Analysis from the Phase 3 PHOENIX Trial

Patients with high BCL2/MYC coexpression non-germinal center B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL) may be more responsive to a therapeutic regimen of Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment, according to analyses of baseline biopsies from the phase 3 PHOENIX trial published in Blood Advances. 

“Our goal was to identify patients with high BCL2/MYC coexpression and to determine whether there was a correlation between the expression data and EFS and OS in the overall population and in patients aged <60 and ≥60 years, respectively,” stated Peter Johnson, MD, Southampton General Hospital, Southampton, United Kingdom, and coauthors.

The analysis assessed high BCL2/MYC coexpression by RNA sequencing, using baseline biopsies from the PHOENIX trial, which assessed the addition of ibrutinib to R-CHOP treatment among patients with untreated non-GCB DLBCL. Kaplan-Meier estimates, Cox regression, and log-rank testing were utilized to correlate BCL2/MYC RNA expression with efficacy outcomes among these patients. 

In the PHOENIX trial, 234 patients exhibited high BCL2/MYC coexpression. A total of 123 patients were administered ibrutinib plus R-CHOP, and 111 patients were administered R-CHOP alone. Results indicated that event-free survival was significantly improved among patients with high BCL2/MYC coexpression who received ibrutinib plus R-CHOP compared to R-CHOP alone, but that there was no notable effect on overall survival. Notably, however, both event-free survival and overall survival improved among patients <60 years old with BCL2/MYC expression who received ibrutinib plus R-CHOP compared to R-CHOP alone. 

The results of this analysis support the notion that high BCL2/MYC coexpression as a subset of patients with non-GCB DLBCL may indicate preferential responsiveness to ibrutinib therapy. 

Dr Johnson and coauthors concluded, “Ibrutinib plus R-CHOP improved the [event-free survival] in patients with BCL2/MYC high-expressing non-GCB DLBCL, as well as the [event-free survival] and [overall survival] in the subset aged <60 years—a finding that warrants further investigation.”

Source: 

Johnson P, Balasubramanian S, Hodkinson B, et al; Clinical impact of ibrutinib plus R-CHOP in untreated DLBCL coexpressing BCL2 and MYC in the phase 3 PHOENIX trial. Blood Adv 2023; 7 (10): 2008–2017. doi:10.1182/bloodadvances.2022009389