What options are available if a diffuse large B-cell lymphoma (DLBCL) patient doesn’t respond to treatment or relapses? Dr. Justin Kline discusses potential next steps in treatment for DLBCL patients with relapsed or refractory disease.
Dr. Justin Kline is the Director of the Lymphoma Program at the University of Chicago Medicine. Learn more about Dr. Kline, here.
Let’s talk about if someone doesn’t respond to initial treatment or they relapse. Let’s start by defining some terms for the audience. What does it mean to be refractory?
So, refractory is a term that’s used to describe a situation where a person has received treatment but that treatment hasn’t worked as well as we have expected. And the most – probably the most important scenario is after initial treatment.
Most people, for example, who receive R-CHOP, somewhere between 80 and 85 percent will have a completely negative PET scan after treatment. That’s remission. If the PET scan is not negative and you do a biopsy and it shows that there’s still lymphoma there, that’s what’s called primary refractory. In other words, the person’s lymphoma was refractory to initial or primary treatment. And in clinical trials that are testing agents, drugs or immunotherapies in folks who’ve had multiple treatments, usually refractory is used to define someone who has either not responded or has had a very, very short response to whatever the last treatment they had was.
How does relapse then differ from refractory?
So, right, so relapse suggests that the lymphoma at some point was in a remission, right?
And so for example, a person gets six treatments of R-CHOP, has a PET scan at the end, the PET scan is clean. We say you’re in remission. Eight months later, the person develops a newly enlarged lymph node, and a biopsy shows that the lymphoma has come back, right? That’s what we would call a relapse. There was a period of remission, whereas refractory usually means there was never a period of remission to begin with.
Got it. How typical is it for a patient to relapse?
Well, again, if you look at all comers, if you treated 100 people with DLBCL, most, probably 70 to 75 percent, would go into remission. About 10 or 15 percent would have primary refractory disease and another 10 or 15 percent would have a remission that would end at some point and they would have a relapse. So, it’s not terribly common.
The problem is that once the lymphoma has either demonstrated that it’s refractory to treatment or it’s come back, it’s relapsed, it’s a little bit more difficult to cure the lymphoma at that point.
How are patients treated then if they’ve relapsed or refractory?
Well, so for somebody who’s had primary refractory lymphoma or has a lymphoma that’s relapsed after initial therapy, again, say for the sake of argument with R-CHOP, for many, many years, the next line of treatment if you will was to administer what we call salvage chemotherapy, and this is different chemotherapy from the original R-CHOP, that’s meant to put the lymphoma back into remission. In other worse, to salvage a remission. And for folks whose lymphomas were sensitive or responded, shrunk down to that salvage chemotherapy, we would consolidate that remission.
We would make it deeper using high dose chemotherapy and an autologous or a cell, stem cell transplant. And that’s been the standard of care for younger patients for decades.
That paradigm has been challenged, particularly in refractory patients or those who have very early relapses after R-CHOP, by two important clinical trials that have demonstrated superiority of a type of immunotherapy, a cellular immunotherapy called CAR T-cell therapy, which seems to be more effective even than stem cell transplantation in that population of folks.