Jia Ruan, MD, PhD
Investigators have determined that the combination of lenalidomide (Revlimid) plus rituximab (Rituxan) can achieve a high rate of complete response (CR) and minimal residual disease (MRD) negativity when used as an initial treatment for patients with mantle cell lymphoma (MCL).
The 5-year follow-up analysis of a phase II multicenter study of lenalidomide plus rituximab as first-line treatment for patients with MCL presented at the 2017 ASH Annual Meeting showed durable remission and MRD negativity beyond 4 years.
Previous results have shown that this combination induces an overall response rate of 92% and a CR rate of 64%, warranting further investigation in a phase III trial, according to lead investigator Jia Ruan, MD, PhD.
“It is a very exciting time for clinicians and scientists working in the field of MCL, but even more importantly, it is very exciting for the patients,” said Ruan, an associate professor of clinical medicine at Weill Cornell Medicine/NewYork-Presbyterian Hospital.
In an interview with OncLive during the meeting, Ruan discussed the pivotal analysis of this combination, as well as the next steps for this regimen in the field of MCL.
OncLive: Can you provide some background on this study?
: At the 2017 ASH Annual Meeting, we reported the long-term outcome of a phase II multicenter pilot study with the combination of lenalidomide plus rituximab as initial treatment for patients with MCL. We started this study in 2011 because we wanted to explore the combination of novel agents that are free of chemotherapy, which could provide an option that is not only effective but also convenient and can be used in an outpatient setting. We know that lenalidomide has activity in MCL, as does rituximab maintenance. In fact, they both extend survival for patients who have MCL, so it makes sense to combine those 2 agents.
Our study design includes both induction and maintenance phases. The induction phase uses those 2 agents—lenalidomide 3 weeks on, 1 week off—and rituximab once weekly for the first cycle and then every other cycle. That goes on for 12 treatments, and subsequently patients who have a response will go on to receive maintenance therapy with both agents. Patients can stay on treatment chronically, but they have the option to stop treatment in 3 years.
We have reported the efficacy of this combination in a previous paper that was published in the New England Journal of Medicine in 2015. In that study, we showed that this combination has very high response rates. The overall response rate was over 90% and the CR rate was over 60%. In the long-term follow-up presented [at the 2017 ASH Annual Meeting], we reported long-term survival outcomes, which showed that the duration of response is very impressive.
At 4 years, 70% of patients remained in remission and 83% are alive and have good quality of life. In addition, we report the MRD assessment, which will essentially allow us to see what depth of treatment responses those patients can potentially achieve. In 10 patients who had over 3 years of treatment, we saw that 80% of them can achieve MRD-negative CRs, which is very promising. This not only reflects on how promising the combination is, but also allows us to ask further questions. Can we, at some time, stop treatment or use a response-adaptive approach to provide chronic therapy?
Finally, we looked at the side effect profile with chronic maintenance treatment, and we did not see any unexpected signals. The majority of patients can be managed in an outpatient setting, and their side effects can be adjusted using dose modifications. We are very excited to report the long-term outcomes of this very effective combination of lenalidomide and rituximab.
Again, because this is a phase II pilot study, we are hoping that with the long-term outcomes we can inspire more interest and momentum to conduct larger studies, either with this combination alone in comparison with other active regimens or building on this combination by adding additional novel agents. All of these would contribute to better outcomes for patients with MCL.
Are there any next steps with this study?
We are hoping that there will be additional large studies that evaluate this combination with a larger patient population. We would also hope that we could conduct a randomized study using this combination with other potentially active novel agents, or low-intensity chemotherapy that can be easily provided in the outpatient setting.