Andre Goy, MD
With the excitement of the recent FDA approval of acalabrutinib (Calquence) still moving through the field of mantle cell lymphoma (MCL), there was much anticipation for additional abstracts in the field at the 2017 ASH Annual Meeting.
For example, in addition to the acalabrutinib data, there were data presented on the combination of lenalidomide (Revlimid) plus rituximab (Rituxan), which showed that patients treated with this combination had a high rate of complete response (CR).
In an interview with OncLive
during the meeting, Andre Goy, MD, chairman and director, chief of Lymphoma, and director of Clinical and Translational Cancer Research at John Theurer Cancer Center, Hackensack Medical Center, shed light on some of these studies as well as future treatment options for patients with MCL.
OncLive: Can you discuss some of the data in MCL that were presented at this year’s meeting?
: At the 2017 ASH Annual Meeting, we have shown the continued progress on the impact of novel therapies, cellular therapies, and immunotherapies. In MCL, we are seeing a continuous shift of novel agents that are changing the landscape as we combine them in the relapse setting, and potentially in the frontline setting.
The long-term follow-up of ibrutinib (Imbruvica) was presented at the 2017 ASH Annual Meeting, which was a report at 3.5 years of several hundred patients receiving the agent in the relapsed/refractory setting. The CR rate was up to 26%, and at 3 years, one-quarter of the patients still had not progressed.
We tried to dive deeper into what could help us predict which patients would do well on ibrutinib. It is interesting, although ibrutinib works in patients regardless of the number of prior therapies…the duration [of response] is clearly affected by the number of prior therapies. Therefore, if you had 1 prior therapy, there was significant difference in outcomes in terms of duration of response and progression-free survival (PFS). These are very powerful data of single-agent ibrutinib in a large group of patients.
During the same ASH session, we had data from the second-generation BTK inhibitor acalabrutinib, which is a more selective inhibitor with probably a better coverage of BTK. What was interesting in this trial was the 80% overall response rate with a 40% CR rate. The criteria of the trial were slightly different than that of the ibrutinib trial, and the safety profile was better—there was no atrial fibrillation in over 100 patients. The rest of the toxicity profile pretty much overlapped with that of ibrutinib.
What we are starting to see are combinations with these biological agents because they are not curative alone in MCL. Although we achieve some CRs with patients eventually progressing, combining these agents might achieve a deeper response. [There was] a pilot study presented at ASH, which was a combination of rituximab (Rituxan), lenalidomide, and ibrutinib, and the response rate was over 85% and the CR rate was 60%. That is very promising for patients who have relapsed or refractory MCL. This is what we are going to see moving forward because achieving a deeper response in MCL clearly affects the outcome. There are ongoing trials trying to develop combinations on nonchemotherapy options, particularly in the frontline setting for elderly patients with MCL who are not candidates for chemotherapy.
I also want to mention updates from the multicenter trial looking at the long-term follow-up of lenalidomide and rituximab. It is a small study but, as a proof-of-concept trial, it was interesting that at 5 years there were still some patients who continued in remission on rituximab or off it.
Finally, there was a presentation on maintenance rituximab, which is part of a large randomized trial of rituximab, fludarabine, and cyclophosphamide versus R-CHOP in the frontline setting in patients who are elderly or ineligible for high-dose therapy and transplant. The results are very impressive, and not surprisingly, the maintenance with rituximab was better tolerated and had better results in terms of PFS and OS.