In this video, Nathan Fowler, MD, MD Anderson Cancer Center, Houston, Texas, discusses the results of of phase 2 study that evaluated the activity and safety of ibrutinib in combination with rituximab in untreated follicular lymphoma (FL).
Transcript
Hi. I'm Nathan Fowler from the MD Anderson Cancer Center in Houston, Texas. Today, I wanted to share with you a little summary of a recent article that was published in the British Journal of Hematology, where we reviewed the results of a phase II trial of Ibrutinib and Rituximab, in patients with untreated follicular lymphoma.
As many of you know, follicular lymphoma is a disease with a very heterogeneous course. Patients can often do well, or sometimes, unfortunately, have not so great outcomes, regardless of therapy.
Many patients who are diagnosed with follicular lymphoma are older, many of them have comorbid conditions, and many of them cannot tolerate chemotherapy as a backbone, especially as the initial therapy. This trial combined two drugs which have activity in low-grade lymphoma.
It's a drug called Ibrutinib, which is a BTK inhibitor, along with Rituximab, which is an anti-CD 20 monoclonal antibody that is often used in the treatment of follicular lymphoma across different lines of therapy.
Now this study was a phase II study. It was multicenter, and it enrolled 80 patients in two different cohorts. The first cohort gave all patients Ibrutinib at 560 milligrams continuously, along with Rituximab given once weekly. Now patients received Ibrutinib until disease progression.
The other cohort was an exploratory part, where we were looking to see if we could determine biomarkers for response in patients who received Ibrutinib and had follicular lymphoma.
In this study, we gave an initial two-month lead-in, or I should say, this part of this study, we gave an initial two-month lead in Ibrutinib alone, and then gave the four doses of Rituximab, and then all patients continued on Ibrutinib as a single agent until disease progression.
Today, I'll just talk to you a little bit about the overall results of both of those cohorts, and how it could apply to future therapy for follicular lymphoma. Now, as I mentioned, the study enrolled a total of 80 patients, 60 in the first arm and 20 in the second arm. The average patient's age was 58. We had 26 patients that were over 65.
Nearly all patients had good performance, that's in fact, 74 percent the performance status is zero. Around half of the patients, 40 percent had stage three or four disease. Half of the patients had high-risk flippy scores. 16 percent of patients had bulky disease, again, as defined by a node bigger than seven centimeters and longest axis.
Again, all these patients were previously untreated. When you look at the follow-up, it was around 30 months in both arms. We saw in arm A, that was again, Rituximab initially, followed by continuous Ibrutinib, overall response rate of 85 percent with a complete remission rate of 40 percent, partial remission rate of 45 percent.
In that arm, the progression-free survival is 41 months at a median. Arm two, again where we delayed the Rituximab, the overall response rate was 75 percent with the complete remission rate of 50 percent. The median progression-free survival has not yet been reached in that arm. Overall survival median has not yet been reached in either arm.
Now, the drug was very safe, as you would expect. We didn't see a lot of adverse events, actually not a lot of significant adverse events. We had several patients who stopped the study. The majority of the cases that stopped the study were due to progression of disease.
When you look at more specifics, with regards to the adverse event profile, the most common was fatigue, which was seen around 70 percent in both arms. We also saw some diarrhea occurring, and this was almost always grade one or grade two.
We saw some myalgias, which occurred in around 20 to 30 percent of patients. Of the vast majority of these cases were a grade one or two. A little bit of rash, 30 percent in arm one, only 5 percent of them were grade three or grade four.
As I mentioned, almost all patients were able to continue on drug, very few stopping due to adverse events from the drug. We did see atrial fibrillation. That was quite uncommon. That occurred in only two...I should say, either atrial fibrillation or atrial flutter, in only two patients on the trial.
How do we think about this combination? It looks very good, in patients with newly diagnosed follicular lymphoma. I'll mention that these patients did not require GELF criteria to enter on trial. We know that for example, Rituximab, as a single agent is also active in these patients.
The complete remission rate, again, around 40 to 50 percent, was higher than we generally see with Rituximab as a single agent. The progression-free survival at over three years, median in both arms, looks very good compared to, for example, a single agent of Rituximab.
Now, this is a phase II trial. The only way we can confirm whether this adds benefit to Rituximab is to do a randomized phase III trial. That trial is ongoing. It's called the perspective trial. It's looking at Rituximab plus placebo, versus Ibrutinib-Rituximab, the same regimen that we saw in this phase II trial.
It's looking at newly diagnosed follicular lymphoma, and focusing on patients that are older, or patients who have comorbid conditions. I think again for that population who often doesn't tolerate chemotherapy, this is a real good option, especially if the randomized study shows that Ibrutinib adds benefit to Rituximab as a single agent.
I'd like to thank you for your attention, and I encourage you to check this out. It is both in print and online at the British Journal of Hematology. Thank you.
