Therapy Initiation Prior to Cytogenetic Testing Results

Brian Hill, MD, PhD: We learned about diffuse large B-cell lymphoma over the past several years. It goes back to the recognition that really this is not a single disease entity but actually represents different types of lymphomas that collectively are referred to as diffuse large B-cell lymphoma. More specifically it’s been recognized that there is 1 type called germinal center subtype, and another ABC [activated B-cell] subtype, which have different biological features and different outcomes, with ABC subtype having the worst outcomes in germinal center subtype.

Over the past couple of years, we’ve done to identify that this is really an oversimplification of the subtyping, and with advanced molecular tests, next-generation sequencing, and high throughput genomic analysis, 2 separate groups of independently identified diffuse large B-cell lymphoma as really having a number of different subtypes. Germinal center is actually going to be divided into 2 different groups: worse and better outcomes. Similarly, ABC subtype can be divided into at least 2 or more subgroups, some of which have better outcomes than others.

From a practical perspective, I would say in 2020 to really approach diffuse large B-cell lymphoma the same way with the notable exception of double-hit lymphoma, is probably a germinal center–derived subtype of diffuse large B-cell lymphoma that tends to have a more aggressive course.

The question about initiating treatment before receiving the cytogenetic results is an important one. If you know that a patient has diffuse large B-cell lymphoma and they need immediate treatment, the standard of care still is R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] and chemotherapy for frontline therapy outside of our clinical trial. If you don’t have the cytogenetic results to know that the patient takes double-hit lymphoma, it’s still reasonable if the patient has a clinical urgency to initiate treatment with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] and then potentially escalate a more intensive regimen such as dose-adjusted R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride] with subsequent cycles.

Turnaround time of getting these molecular tests back can be shorter or longer, depending on if the patient is being seen at a high-volume center or a community center. Many community centers send out the FISH [fluorescence in situ hybridization]test for the MEK, BCL2, and BCL6 translocations. And there may be a longer turnaround time. But again, I wouldn’t let that delay prevent me from initiating treatment if there’s a clinical urgency to start therapy. It’s perfectly fine to start with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] and then subsequently change after you have the results of those molecular tests.

Transcript Edited for Clarity