In this video courtesy of VJHemOnc, study author Jia Ruan, MD, PhD, of Weill Cornell Medical College in New York City, discusses the 7-year follow-up of a multicenter, phase II study evaluating the efficacy and safety of the so-called R2 regimen — lenalidomide (Revlimid) and rituximab (Rituxan) — in mantle cell lymphoma (MCL). Updated findings were reported at the American Society of Hematology (ASH) annual meeting.
Following is a transcript of her remarks:
We’re very pleased to report and share that the long-term follow-up data of our phase II multicenter study with a combination of lenalidomide plus rituximab for patients with untreated mantle cell lymphoma who required treatment. This study was designed to look at efficacy and also safety data of this biological doublet as frontline therapy.
The study started about 10 years ago, just around the time when the novel agent lenalidomide was approved for application for patients with mantle cell lymphoma. And, as you know, mantle cell lymphoma is a distinct subtype of B-cell non-Hodgkin’s lymphoma, which does not have a standard one-size-fits-all treatment induction option.
And, for patients who are young and fit, the mainstay of the treatment was intensive chemoimmunotherapy, which was not curative and comes with typical chemotherapy-associated dose-limiting toxicity. And it was not applicable broadly for all patients.
So we asked the question if non-chemo-based biological combination with novel agents can be effective as initial therapy for patients with mantle cell lymphoma, and we looked at the combination of lenalidomide plus rituximab doublet, because we would like to provide more broadly applicable applications for patients who may not be good candidates for intensive chemoimmunotherapy.
Those included patients who are elderly, those with pre-existing medical illnesses, and also those who simply wish to avoid chemotherapy. And they were looking for alternatives that could be effective, well-tolerated, safe, and conveniently delivered in the outpatient setting, and broadly applicable for all patients if they come around needing treatment for mantle cell lymphoma.
Just to recapitulate, the treatment program included two treatment phases. The first is induction, which involved lenalidomide starting at 20 mg daily, 3 weeks on and 1 week off for a 28-day cycle, and rituximab, which was given weekly for the first month, and subsequently every other month.
After 12 cycles, those patients move on to maintenance, which would be getting a lower dose of lenalidomide, usually up to 15 mg, but could be lower at 3 weeks on, 1 week off, and rituximab continuing every other cycle. The study was designed such that there was the option to discontinue study treatment after 3 years, if those patients remained in remission.
So, previously we reported very high response rates with this doublet combination. The best overall response was achieved at 92% with a CR [complete response] rate at 64%. And subsequently we reported that the response appears to be quite durable in the 5-year follow-up study, at which time we also measured the MRD [minimal residual disease] by a high precision next-generation sequencing method.
In those patients, 80% had MRD negativity. Perhaps the high-quality response was associated with the durability of the steady outcome.
So at this year’s ASH, we were very pleased to share that 7-year follow-up, which continued to demonstrate durable responses.
In the patient subset population, about half of those patients continue to be ongoing responders, and about half of them actually were able to discontinue treatment and remain in remission, which was quite remarkable.
The other half were receiving a treatment at a somewhat modified dose. For example, some were getting a single agent, rituximab, maintenance, others were receiving lenalidomide at a modified dose based on side effect profile.
The 7-year overall survival now was measured at 73% and a 7-year progression-free survival with 60%, which is quite remarkable. We have patients now the longest on treatment for 10 years, and doing well with good quality of life.
So, I think the conclusion that we have, based on our long-term study evaluation with that, this is a first study and actually the longest ongoing study available for biological combination and not a traditional chemo-based biological combination. And the rituximab-plus-lenalidomide combination appears to be safe and effective.
And, as the induction and maintenance strategy in frontline setting, the long-term continuous treatment appears to be feasible with lenalidomide at dose modification. We think that this biological doublet should be studied in a larger study and preferably compared with traditional chemoimmunotherapy for patients with mantle cell lymphoma in the frontline setting.
Currently, we and others are continuing to work on optimizing novel treatment options, including in the frontline setting. For example, we’re looking at adding novel agents into the R2 combinations, or treatment synergy.
We’re also looking at other research questions. For example, because of the feasibility of long-term application of oral outpatient-based novel treatment, how can we adjust treatment intensity and duration based on response quality.
In doing so our goal is to optimize efficacy, and at the same time, continue to minimize toxicity, and this will help improve outcomes and also continue to preserve quality of life for patients with mantle cell lymphoma.