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Dr Strati Highlights Lenalidomide Plus Rituximab for FL
Paolo Strati, MD, Assistant Professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, highlights long-term follow-up results of lenalidomide and rituximab as initial treatment for patients with follicular lymphoma (FL).
Transcript
Dr Strati: My name is Palo Strati. I'm an assistant professor in the Department of Lymphoma Myeloma, Departmental Translation of Molecular Pathology at MD Anderson Cancer Center in Houston, Texas.
OLN: What existing data led you and your co-investigators to conduct this research?
Dr Strati: Chemoimmunotherapy with either R-CHOP (rituximab plus cyclophosphamide, vincristine, doxorubicin, and prednisone) or BR (bendamustine plus rituximab) currently represent the standard frontline treatment for patient with previously untreated high tumor burden FL in the United States.
This is based on 2 large, randomized phase 3 studies, the Bright and the Still study, that were conducted in Europe and the US, respectively.
More recently, there's been an additional randomized phase 3 study where chemoimmunotherapy—Again, either R-CHOP or BR—has been compared to immunotherapy with lenalidomide, an oral agent, able to overall activate immune system and increase its antitumor activity with rituximab overall, called R2, with previously untreated, high tumor burden advanced stage FL.
Unfortunately, the way this randomized phase 3 study was designed was as a superiority study. R2 was not superior to chemoimmunotherapy. Technically, the study was negative. The FDA has not yet approved immunotherapy with R2 as a frontline option for these patients.
However, clearly data demonstrated the immunotherapy was non-inferior to chemoimmunotherapy.
Based on that, NCCN guidelines allowed the United States use of R2 as frontline treatment for these patients. This has happened only for the last few years. So as opposed to chemoimmunotherapy, for which now we have relatively long follow-up, we don't really know what the long-term outcome of patients with advance stage FL who received frontline R2. That was the reason why we decided to look into this for this project.
OLN: Could you briefly describe the study and its findings?
Dr Strati: About 10 years ago, Dr Nathan Fowler, one of the investigators with interest in FL, working in our institution and the Anderson Cancer Center in Houston, Texas, has initiated a phase 2 study where immunotherapy with R2 was given to patient with previously untreated advanced stage FL, grade 1 to 3a. Of interest in that study, also a small percentage of patient (had) low tomor burden—so patients who did not meet GELF criteria were also included.
Patients received R2 from 6 to 12 months, initially 6. They were followed for an extensive amount of time. This study was already published many years ago.
What we did for the purpose of this project was to publish the long-term data of the 70 patients who were enrolled this study. This was a 10 year follow-up, so a very long term follow up for immunotherapy frontline treatment with patient with FL—that as I mentioned before, has not been reported by any other group.
What we saw was with immunotherapy, up to 70% of patients were still treatment-free 10 years after initial treatment. We tend to say that FL remains incurable. Findings like this challenge this paradigm.
We also saw that there was no baseline characteristic that would help us to understand, while patients were going to be long-term responders to frontline immunotherapy with R2. The only thing that did associate with a significantly longer progression-free survival (PFS) was the ability to achieve a complete response (CR) during immunotherapy.
Trying to increase the rate of those patients is going be extremely helpful.
OLN: Were any of the outcomes particularly surprising?
Dr Strati: The most surprising outcome, in my opinion, was very high disease-free rate (of) 10 years after initial immunotherapy.
As mentioned before, we keep saying that patient with FL cannot be cured, but in immunotherapy, and more recently also cellular therapy, may completely change this narrative.
We don't see a clear plateau, definitely for patients who are able to achieve a CR. We don't really see any relapse at 10 years after initial treatment. So again, it may overall change the way we tell the story, about patients with FL.
OLN: What are the possible real-world applications of these findings in clinical practice?
Dr Strati: There are a couple of possible clinical implication from these findings.
The first one, as I mentioned before is, according to the NCCN guidelines, even if R2 is not approved by the FDA as frontline treatment, it can be used. A majority of insurances will approve it as frontline treatment for patient with advanced stage high tumor burden FL.
The very high rate of disease-free state, 10 years after incisional treatment with possibility of cure for these patients, supports the possible clinical implication that more and more physicians should provide front line R-square, and then a chemotherapy-free approach for a patient with FL.
As we all know, Yescarta (axicabtagene ciloleucel) the only cellular therapy currently approved by the FDA for a patient with FL is based on the use of autologous T-cells. It's very important to preserve their fitness as much as possible. Being able to provide in first and second line chemotherapy-free approaches may potentially preserve the fitness and overall increase the efficacy of a potential approach, such as cellular therapy, afterwards.
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