Centering discussion on a patient scenario of relapsed/refractory follicular lymphoma, key opinion leaders consider how they would select best available therapy in this setting.
Sameh R. Gaballa, MD: Let me give you a patient scenario. Let’s say you get a patient who’s in their 80s, for example, an 83-year-old. They come in, they were diagnosed with low grade follicular lymphoma, grade 1 or 2, 3 years ago. At that time they got rituximab single agent, they had relatively bulky disease. They achieved a PR [partial response], and they’re stable for the next 2 to 3 years. But now they’re slowly progressing for the last year. Say they’re symptomatic, they have lower extremity edema from pelvic adenopathy. This patient, say they’re elderly and they live far away from an academic center. What would be your approach for such patients? Would you consider single-agent rituximab again, obinutuzumab, or an oral therapy? How do you treat these patients?
Matthew A. Lunning, DO, FACP: That’s a very practical case scenario in follicular lymphoma. Not all follicular lymphoma is bad follicular lymphoma that’s rapidly progressing when you’re sitting here asking yourself, is there transformative disease? But you can have that slow, insidious follicular lymphoma, as you alluded to here, which in patients, we have to remember that the median age is in the late 60s, early 70s. These patients’ odds are that they’re going to die with their follicular lymphoma, not of their follicular lymphoma, but still it could be quality of life altering, as it is in this patient. So looking at this subject, who got rituximab monotherapy and had disease control, but as you would expect, coming out of our monotherapy had some residual adenopathy. Then you’re asking the question, is it still behaving like a snail, or is it transforming into a cheetah? From the case description, I always ask myself, do I think this patient is transforming? Because that sets the tone for the discussion, and it sounds like it’s still acting like a snail, but even snails can cross the treatment finish line again.
In regard to using rituximab monotherapy again, I’m a bit hesitant, just based upon the RESORT [trial] data, that I’m going to get good mileage out of rituximab again. In the second and the third line, you do see the law of diminishing returns with rituximab. It’s not to say that it can’t work, but I wouldn’t use it to say that we’re going to get a couple more years out of rituximab again. So then do you partner something with rituximab or switch to obinutuzumab-based combinations? Or is there a different therapy that could be well tolerated in that case? If I’m thinking about adding something to a CD20 backbone, I think that lenalidomide, as in the AUGMENT [study], would be a reasonable discussion, but I think a lot of the toxicities are driven by the lenalidomide. In an 83-year-old individual, I would pay very close attention to their creatinine clearance. In the AUGMENT trial, patients were allowed to go on the study if their creatinine clearance was less than 60 [mL/min], but you had to dose adjust lenalidomide appropriately from 20 mg down to 10 mg. Truly, there’s a right dose for everybody for lenalidomide. I’m just not sure in follicular lymphoma that it’s always 20 mg. Patients better tolerate it if they’re appropriately dosed for their lenalidomide, understanding that now we can go all the way down to 2.5 mg based upon our NDS [National Drug Control System] availability of that dose. That would be part of the discussion.
The other discussion truly is tazemetostat in this population of a patient who wants an oral therapy that, based upon the data and the clinical trials, could be well tolerated and could have the potential for activity. One of the things I find interesting about tazemetostat is when patients are progressing, it doesn’t appear to be transformation that they’re progressing with, it appears to just be their follicular lymphoma. I don’t think you lose anything or you take anything off the table by giving tazemetostat, or sequencing it as R-squared [rituximab and lenalidomide] followed by a plan of tazemetostat. Still it sounds like this patient might be a clinical trial candidate, if they’re willing to travel for some sort of trial from that standpoint.
Sameh R. Gaballa, MD: I completely agree, Dr Lunning. These patients are always not the same, you have to personalize each decision. Just as you mentioned, patients could come in with comorbidities, or they could be coming in like an 83-year-old patient, but functionally speaking, they’re functioning at a much younger age. Or they could have a lot of comorbid conditions that make us try to think about which treatment is appropriate for such a patient. In terms of single-agent therapy, obinutuzumab can sometimes be an option as well for these patients. This patient technically is not rituximab refractory, but exactly as you mentioned, you get diminishing returns with each subsequent line of therapy. Sometimes what you need is more of a stable disease. Although with this patient, I agree with you, you probably want to be a bit more aggressive since they’re symptomatic and you need to shrink their lymph nodes because of the lower extremity edema. I completely agree, something like tazemetostat oral therapy can be an option here as well, if the patient wants an oral therapy, they don’t want to come in for infusions, they live a bit far away from an academic center or from a local oncologist. Bispecific antibodies probably will have a role there. For the elderly patients, at least the CRS [cytokine release syndrome], particularly within the first 2 cycles, we’ll have to think about how do we care for these patients in the community? At this point, at least where I’m practicing, the bispecifics are still done more at academic centers, but I see in the near future, these treatments being done within the community setting as well.
Matthew A. Lunning, DO, FACP: I agree with you. I think that bispecifics are going to have a steep learning curve. There are some institutions who learn through the clinical trials and are adapting it to the commercial environment very well. But the slope of that curve will flatten over time as it gets out there and you dip your toe into the water with the appropriate risk-benefit patient, and then we’ll see the full impact.
Transcript edited for clarity.