Andre H. Goy, MD, MS, chairman of John Theurer Cancer Center, from Hackensack University Medical Center, discussed ways to address the challenge of extending survival for patients with diffused large B-cell lymphoma (DLBCL) who achieved a complete remission (CR) at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition, held December 7-10, in Orlando, Florida.
It’s an important question, looking at how we can improve the outcome of patients who achieve a complete remission with R chemo immunotherapy induction in large cell lymphoma. What we know is that the distinction that we have been doing it for over a decade now, almost 2 decades, is the distinction between GC [germinal center] or non-GC, or ABC [activated B-cell] and GC, those are the 2 main subtype of large-cell lymphoma. Knowing that the ABC subtype or non-GC has a worse outcome without CHOP, but we know that now that the patient will achieve a CR, have the same outcome, if they are GC or non-GC. So, the issue is actually to improve the patient who have an early failure. We know now the patient who have large-cell lymphoma, 80% of the relapse occur early. So, this is a real challenge. And there’s a number of histologies that are being looked at, and we know that maintenance therapy after achieving a CR has no real impact on overall survival.
There was an improvement in PFS using a randomized trial from Europe, but it had no impact on survival and this was after R-CHOP chemotherapy. We know that maintenance rituximab (Rituxan) really has no impact except on the regional disease when comparing R-CHOP vs CHOP, the patient who had received just CHOP and received rituximab afterwards did better than if they did not. There was some data that looking at maintenance in a patient who, in a large randomized trial from Europe, again after R-CHOP and men, because they seem to have a faster clearance of rituximab might have some benefit. I don’t think that this has any meaningful impact in practice. What we know is that, and it’s not again ready for prime time, is that the patient in the immune study who was post R-CHOP is very critical and the patient who have a ratio lymphocele to immunocyte from data from mayo clinic but other investigators as well seem clearly to have, regardless of a response, seem to have a much worse outcome and you see sort of a reflection of the immune studies in post chemotherapy, post induction. But we don’t really have a good way to try to handle this and on how we treat this. In the future with more immunotherapy, definitely that will be an area of opportunity.
I think the most appealing data is the cell-free DNA data. The cell-free DNA data that we actually see at ASH this year and I think finally is confirming of previous observation from Stanford is that all patients, regardless of the stage have detectable cell-free DNA and that usually correlates with the IPI [International Prognostic Index] in the bulk of the tumor and the patient responding well can become cell-free DNA negative so you want to have a way to try to really improve the evaluation of the CR. So, the patient, to your point, the patients who are CR by standard definition of PET imagining basically… if they are cell-free DNA negative and PET negative they really do very well. But the patients who are cell-free DNA positive are, still don’t do as well. So, this is certainly an area of opportunity to try to improve the outcome of these patients.