A complex therapy for diffuse large B-cell lymphoma has shown no improvement over the current standard of care, but raises important questions about how heterogeneity in this type of malignancy impacts response to treatment, according to a new study published in the Journal of Clinical Oncology.
These findings should influence future clinical trial design, said Jane Winter, MD, ’82 GME, professor of Medicine in the Division of Hematology and Oncology, member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, and a co-author of the study.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive but common lymphoma that develops from B-cells in the lymphatic system. The drug regimen of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) has been the standard of care since the early 2000s, but poor outcomes for patients with recurrent DLBCL has prompted efforts to improve first-line therapies.
A more complex therapy designed to better treat recurrent disease was developed at the National Cancer Institute: a combination of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). Early trials showed it to be effective in both medical center and community settings, and the current study is the first to report on its long-term outcomes when compared to the standard of care, R-CHOP.
Despite DA-EPOCH-R’s more complex drug administration and greater toxicity, the investigators found no significant difference in rates of progression-free survival among the aggregate study population. For example, the two-year survival rate for patients in the DA-EPOCH-R group was 79 percent, compared to 75 percent for patients in the R-CHOP group. Although the highest risk patients appeared to do better with DA-EPOCH-R, the study was not designed to look at individual risk groups – and the number of high-risk patients was low overall.
Interestingly, survival rates in this trial were overall much higher when compared to other large-scale DLBCL studies. This could indicate an under-enrollment of higher risk patients or greater biologic diversity in the disease than was previously thought. According to the authors, this topic is ripe for future investigation.
“We now understand the cancer is even more heterogeneous than when this trial was designed,” the authors wrote. “Future study involving the NCI’s National Clinical Trials Network will identify molecular subsets of the cancer and determine if specific therapies offer differential benefit.”
This study was supported by NCI of the National Institutes of Health grants U10CA180821, U10CA180882, U10CA180847, U10CA180833, U10CA180799 and U10CA180820.
