The most common form of non-Hodgkin lymphoma is diffuse large B-cell lymphoma (DLBCL). DLBCL is a fast-growing cancer that grows in B cells, the immune cells that make antibodies to fight infection. Over 18,000 people are diagnosed with DLBCL in the United States each year.
One subgroup of DLBCL is characterized by a genetic pattern described as “activated B cell-like” (ABC). Tumors of the ABC subtype require chronic B cell receptor signaling, a function inhibited with a targeted therapy called ibrutinib.
A new study published in Cancer Cell suggests that a targeted therapy called ibrutinib administered in combination with a standard chemotherapy regimen significantly benefits some DLBCL patients. Although DLBCL is most common in adults over 60 years, the study focused on patients under 60. This cohort that demonstrated a survival benefit in a previous Phase III trial, the Phoenix Trial, investigating a similar combination therapy.
All patients received standard R-CHOP chemotherapy consisting of rituximab, cyclophosphamide, hydroxydaunomycin (also known as doxorubicin), oncovin (also known as vincristine), and prednisone. Patients received R-CHOP with or without ibrutinib.
The researchers analyzed biopsies from patients on the Phoenix Trial and identified three genetic signatures, MCD, BN2, and N1, within the ABC tumor samples. When evaluating the MCD and N1 subtypes, the analysis revealed 100% three-year event-free survival in patients under 60 treated with R-CHOP plus ibrutinib. Patients exhibiting these tumor subtypes treated with R-CHOP alone had less than 50% three-year event-free survival.
The exciting data presented in the study strongly promotes new personalized medicine strategies for specific patients with DLBCL. While doctors typically run tests to classify the ABC subgroup, there is no commercial test available to further identify the MCD and N1 subtypes. More personalized strategies may become feasible as we develop a greater understanding of the underlying mechanisms of combination R-CHOP plus ibrutinib therapy. Subtyping tumors could help doctors and patients develop more effective personalized treatment strategies.