Overview of Relapsed/Refractory DLBCL and Management Strategies

Transcript:
Matthew A. Lunning, DO, FACP: Dr Wang, in your practice, are patients with diffuse large B-cell lymphoma [DLBCL] either primary refractory to their frontline therapy or relapsing quickly thereafter?

Yucai Wang, MD, PhD: We typically say we cure about two-thirds of patients with standard immunochemotherapy. It used to be R-CHOP [cyclophosphamide, doxorubicin, prednisone, rituximab, and vincristine], and now we just heard it would probably be pola-R-CHP [polatuzumab , cyclophosphamide, doxorubicin, prednisone, and rituximab], and that left us about one-third of the patients who will have refractory disease or will have relapsed after the initial response. The primary refractory disease has different definitions across different literature, but basically they’re either not responding enough to the frontline therapy, or they’ve relapsed early. You can argue about what’s early, but that’s about probably 10% of patients. Then you have probably another 20% or 30% of patients who relapsed within the first 2 years, but [are] not in a primary refractory bucket. Then at the 2-year mark, we usually say, we’ve probably cured most of the patients, but then if you start the clock again at that point, there is still about 9% to 10% risk of relapse in the next 5 years, counting from the 2-year mark. So, adding that together is probably again one-third of patients who will have refractory or relapsed disease.

Matthew A. Lunning, DO, FACP: Could you rank [the] risk factors [you assess] when you see a new patient to say, this person is at a high risk of having primary refractory or early relapsed large-cell lymphoma?

Yucai Wang, MD, PhD: There are high-risk features that predict less chemotherapy-responsive disease but may not necessarily differentiate when they will relapse or become refractory to the disease. Certainly, the high-risk features, the traditional clinical risks like high IPIs [International Prognostic Index scores], disease bulk, and then, from the molecular standpoint as we just mentioned, the MYC and BCL2 expression or the MYC rearrangement, some of the high-grade B-cell lymphomas, those are the ones. With more sequencing, we’ll probably know [of more] high-risk mutations like TP53. Then as you go to frontline therapy, in the first couple of cycles, probably the kinetics 2 response in the interim, may have some implication, [to] identify those who may relapse later as well.

Matthew A. Lunning, DO, FACP: Dr Saeed, we just heard about the up-front treatment, [that the] paradigm may be changing. There’s been an absolute explosion of treatments for relapse/refractory DLBCL. How has all that energy, all that therapeutic energy that’s been put into the relapse refractory large-cell space, changed your practice over the last several years?

Hayder M. Saeed, MD: It changed the way I look at patients right after treatment with the frontline therapy. At this point it’s important to recognize those patients who have refractory disease, who have positive imaging findings that might need follow-up right after finishing chemotherapy. It changed how I follow up on them right after treatment for the first year or two. It’s important to recognize those patients who relapse early. Unfortunately, I still feel that we don’t have good guidance on how we check and find those patients. I think we still, in clinical practice, must wait for them to have symptoms that would indicate disease relapse. I look forward to hearing more and more about the use of genetic markers in the blood, such as minimal residual disease or cell-free DNA, because I think those will help down the road to recognize those patients earlier so that we can find the best treatment for them earlier. As Dr Wang mentioned, we cure around two-thirds of those patients, but for the last one-third, we must do a better job in recognizing and finding them early because we will open many more doors for them rather than waiting for them to present with significant disease burden before we can intervene and treat them.

Transcript edited for clarity.