Initial Treatment with Lenalidomide Plus Rituximab for Mantle Cell Lymphoma (MCL): 7-Year Analysis from a Multi-Center Phase II Study

At the 2020 Annual Meeting of the American Hematology Society (ASH), the Weill Cornell Medicine mantle cell lymphoma research team presented the 7-year long-term outcome analysis of the first study of a non-chemotherapy frontline treatment regimen with lenalidomide plus rituximab as induction and maintenance therapy for mantle cell lymphoma (MCL).  

The multi-center phase 2 study, led by study chair Dr. Jia Ruan, was initiated in 2011 and previously reported early efficacy in the New England Journal of Medicine (NEJM) and 5-year follow-up results in Blood, which was highly effective with an overall response rate (ORR) of 92%, and complete response (CR) of 64%. It was also well tolerated, with durable responses, including the 5-year progression free survival (PFS) and overall survival (OS) of 64% and 77% respectively. Dr. Samuel Yamshon, a second-year hematology and medical oncology fellow at Weill Cornell Medicine and NewYork-Presbyterian Hospital led the oral presentation of the 7-year follow up analysis at this year’s ASH meeting.

The study treatment is conveniently administered in the outpatient setting, with the oral agent lenalidomide given on days 1-21 of a 28-day cycle and rituximab provided once very other cycle during maintenance. The treatment continues until progression of disease, with an option to stop therapy after 3 years of remission.

A total of 38 clinical trial participants were enrolled at four participating centers across the United States. Of the 36 evaluable patients, 19 (53%) of the patients remain in remission, including 12 (33%) beyond 7 years. Of the patients in remission, 10 remain on treatment, while 9 patients in remission opted to stop therapy after at least 3 years of study treatment due to side effects or patient preference. The median progression free survival (PFS) and duration of response have not been reached. The 7-year PFS rate was estimated at 60%, and 7-year OS rates at 73%. With long-term maintenance treatment, there were no new safety concerns, and close follow up limited toxicity for those who wished to remain on therapy.

The long-term outcome of the lenalidomide plus rituximab regimen represents a major stride in the treatment and care of MCL patients – a population of patients who harbor a rare and generally incurable disease where intensive chemotherapy regimens do not necessarily translate into cure and may not be tolerated by all. It is notable that this combination therapy offers a chemotherapy-free initial treatment approach that compares favorably in outcome to conventional chemotherapy-based regimens such as bendamustine-rituximab, VR-CAP, and R-CHOP with rituximab maintenance. The National Comprehensive Cancer Network (NCCN) has incorporated this evidence into their treatment guidelines for MCL patients. The Weill Cornell Lymphoma Program researchers concluded that the evaluation of this active regimen in larger, randomized frontline trials comparing novel agents with chemoimmunotherapy is warranted. 

704 Initial Treatment with Lenalidomide Plus Rituximab for Mantle Cell Lymphoma (MCL): 7-Year Analysis from a Multi-Center Phase II Study
Type: Oral presentation
Session: 623. Mantle Cell and Indolent B-Cell Lymphoma – CAR-T and immunotherapy clinical studies

Monday, December 7, 2020: 2:30 PM 

ASH 2020 Weill Cornell Medicine Lymphoma Program Conference Coverage

Mantle Cell Lymphoma PALIBR Outcomes Published Online in Blood Journal

The oral Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has become a mainstay in the treatment of mantle cell lymphoma (MCL), producing a response in nearly 70 percent of all patients. Yet, the majority of MCL patients treated with ibrutinib develop resistance to the drug within about a year.

Preclinical research conducted at Weill Cornell Medicine demonstrated that sustained inhibition of CDK4 (a protein that promotes growth of MCL cells) by the oral drug palbociclib can not only prevent proliferation of MCL cells, but also make them more sensitive to attack by ibrutinib.

Based on these findings, Weill Cornell Medicine and NewYork-Presbyterian Lymphoma Program Chief Dr. Peter Martin and colleagues initiated a phase I study of palbociclib plus ibrutinib (PALIBR) in patients with previously treated MCL. Results from the all-oral regimen were recently published online in the American Society of Hematology (ASH) Blood Journal.

The addition of palbociclib to ibrutinib appeared to produce deeper, more durable responses compared to what is traditionally produced by ibrutinib alone, with over half of all patients remaining free of disease progression at the two-year post-treatment mark. The most prevalent side effect was low blood counts.

Weill Cornell Medicine“The first person to be treated on the study in August of 2014 achieved a complete response within three months and remains in a complete response today,” said Dr. Martin. “We were all excited by the results.”

Physicians and researchers at the Lymphoma Program look forward to learning more about the efficacy of PALIBR in the ongoing AFT-32 phase II trial, which incorporates genetic profiling that may help to identify the features associated with drug resistance.

Promising Long-Term Outcome of Chemo-Free Mantle Cell Lymphoma Treatment Published in Blood Journal

The long-term outcome of the first-ever study of a non-chemotherapy frontline treatment approach to mantle cell lymphoma (MCL) was recently published in the American Society of Hematology’s prestigious Blood Journal.

Led by Dr. Jia Ruan, clinical investigators at four medical centers across the United States launched a phase two clinical trial in 2011 to evaluate the novel biological pairing of lenalidomide plus rituximab as induction (initial) and maintenance (relapse prevention) therapy. The team’s treatment goals were to provide disease control and extend survival, while maintaining quality of life.

Read more about the study here.

Of 36 evaluable patients, about 92 percent responded to treatment, with 64 percent achieving complete remission. At five-year follow-up, 77 percent of participants were alive and well, and 64 percent remained free of disease progression.

To determine how well the lenalidomide plus rituximab combination works, the team also measured the status of minimal residual disease (MRD) – the small amount of cancer cells that may be left after treatment that have the potential to lead to relapse. Eight out of a subset of ten evaluable patients tested MRD-negative.

Overall, the chemotherapy-free drug combination has produced durable remission rates with potential to achieve MRD-negative remissions. Chronic maintenance therapy with lenalidomide and rituximab has manageable side effects, including infections, cytopenias (low blood count), and some expected secondary primary malignancies.

This outcome represents a major stride in treatment and care of the MCL patient population, who harbor a rare and generally incurable disease where intensive chemotherapy regimens do not necessarily translate to cure and may not be tolerated by all patients.

Ruan Face“The introduction of novel agents – including the immunomodulatory agent lenalidomide and Bruton’s tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib, which are FDA-approved for MCL – is poised to transform MCL management by making effective ‘chemo-free’ treatment accessible to all patients in both relapsed/refractory and frontline settings,” says Jia Ruan, MD, PhD.