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ENGAGING EXPERTS

Assessing Response to Follicular Lymphoma Treatment

 

Peter Martin, MD, Weill Cornell Medicine, New York, New York, discusses the prognostic value of PET/CT status after long-term follow-up for recipients of first-line immunochemotherapy for follicular lymphoma.

Watch the video on Oncology Learning Network.

Transcript

Hi, I'm Peter Martin. I'm the Chief of the Lymphoma Program at Weill Cornell Medical College in New York. It's my pleasure to be here today to review some of the studies that were presented at ASCO this year, specifically, a few studies that were related to follicular lymphoma.

Given some of the challenges with development of new agents for follicular lymphoma in the current setting, it's interesting that we've been seeing a lot more studies looking specifically at how we might assess and respond to follicular lymphoma (some technologies, for example, PET/CT scans).

There were 2 interesting abstracts presented that did look at PET/CT scans. One of them was looking at PET/CT scan as a response assessment tool in the Gallium trial.

The Gallium trial, again, was a big study in follicular lymphoma comparing rituximab plus chemotherapy versus obinutuzumab plus chemotherapy. The story, I think, is familiar to most people - obinutuzumab plus chemo was a little bit superior, based on PFS, to a rituximab-chemo arm.

In that study with >1000 patients, a subset of them had PET/CT scans done at baseline, and still a few smaller patients, about 519 patients, had an end-of-induction PET/CT scan prior to the maintenance phase of treatment. Of those 519 patients, 76% or 540, achieved a complete metabolic response. Not surprisingly, those patients did better than the patients that did not get a complete metabolic response.

Maybe somewhat surprisingly was the magnitude of the difference.

The 6-year PFS in the complete metabolic response patients was a little over 60%. It was closer to about a quarter in patients that did not achieve a complete metabolic response.

As we're moving into an era where we're trying to predict who's likely to do well and who doesn't, it does appear that end-of-induction PET/CT scan may, in fact, do a fairly reasonable job of discriminating between those who are likely to do well and those who aren't.

Already very early, we can start to pick up some of that. Interestingly, bone marrow biopsies have commonly been used as a response assessment tool in follicular lymphoma. Most clinical trials have even designed to this day will require a bone marrow biopsy to confirm a complete response.

A quick reminder, about half of all people with follicular lymphoma will have bone marrow involvement at their time of start of treatment. In order to say that somebody has a complete response at the end of a clinical trial, they need to get a scan and then a bone marrow biopsy.

Bone marrow biopsies have historically potentially not been very pleasant for patients, or physicians who are doing bone marrow biopsies sometimes discourage people from participating in clinical trials.

Sarah Rutherford, who has already looked at this in the context of the Gallium trial, furthered that question (What is the utility of bone marrow biopsies as a response assessment?) by looking at pooled data from multiple cooperative group studies in CTM network.

Multiple cooperative group trials in follicular lymphoma, and again, consistent with her prior work, showed that somebody who has got and will get a PET/CT scan at the end of treatment, whatever that treatment might be, bone marrow biopsies that are done to confirm that negative PET/CT scan are almost never positive. In the rare instances where they are positive, they don't seem to impact progression-free survival.

So now, multiple studies that have potentially confirmed end-of-induction PET/CT scan is very predictive of outcomes, bone marrow biopsies as a part of response assessment are probably not very useful tools.

Last study I will talk about was an interesting study looking at PET/CT scans to assess bone marrow involvement in grade 3B follicular lymphoma. Grade 3B follicular lymphoma is an interesting subtype of follicular lymphoma.

It's a little bit distinct. In some ways, a little bit more akin to diffuse large B-cell lymphoma and is commonly treated with diffuse large B-cell lymphoma. They're often, in some areas, they're a transformation that may be missed on small biopsies.

These people tend to have a more aggressive lymphoma, managed more aggressively. In this case, the question that the investigators from the Mayo Clinic were asking was do PET/CT scans predict outcomes?

PET/CT scans at the beginning of staging, PET/CT scans, do they predict outcomes? More specifically, if bone marrow involvement is detected by a PET/CT scan, is that associated with outcomes?

They found in a small number of patients, 27 in total, that bone marrow or bone marrow involvement was present in about a third of patients based on a PET/CT scan. Again, that's different from a typical, typically close to 50%, based on bone marrow biopsy.

In this case, PET/CT scan identified it about a third of the time. Not surprisingly, those patients did worse than patients who didn't have bone marrow involvement based on PET/CT scan.

It looks as though PET/CT scan, when it's identifying nodal sites of disease, and specifically bone marrow involvement in grade 3B follicular lymphoma, might identify a particularly high-risk group of people with follicular lymphoma.

What we do with those patients, I think, remains to be debated, but it's interesting to be able to identify somebody I know that this is a person who may have a harder time with it. Those are the studies that I thought were pretty interesting. Thank you.