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

Multi-Center Phase II Study of Oral Azacitidine (CC-486) Plus CHOP As Initial Treatment for Peripheral T-Cell Lymphoma (PTCL)

Today, at the 2020 Annual Meeting of the American Hematology Society (ASH), the Weill Cornell Medicine T-cell lymphoma research team reported the outcome of the first phase 2 study evaluating the novel combination of oral azacitidine plus CHOP as initial treatment for patients with peripheral T-cell lymphoma (PTCL).

This multi-center phase 2 study, led by Dr. Jia Ruan, is the first of its kind to incorporate epigenetic priming with a hypomethylating agent in the frontline setting as a chemo-sensitizing strategy for PTCL. 

The study enrolled 21 PTCL patients, with the majority of them (17 patients) having the diagnosis of angioimmunoblastic T-cell lymphoma, also known as PTCL with T-follicular helper phenotype (PTCL-TFH). This phenotype is known to have recurrent genetic mutations in epigenetic regulation, providing therapeutic targets for hypomethylating agents such as azacitidine. During study treatment, the patients received CHOP on day 1 of each cycle for 6 cycles, while oral azacitidine was given for 7 days prior to CHOP cycle 1, and for 14 days before CHOP cycles 2-6.  The primary study objective was to see if the novel combination would improve complete response rates following 6 cycles of treatment.  

The study treatment was well tolerated with expected side effects associated with CHOP chemotherapy. Eighteen patients were able to complete all 6 cycles of treatment without the need for chemotherapy dose reduction. Ten patients underwent successful stem cell transplant while in remission. Complete remission (CR) was achieved in 75% of clinical trial participants at the end of 6 cycles of treatment, exceeding the pre-determined efficacy threshold (60%) to declare the treatment as effective. Notably, within the subgroup of patients with the PTCL-TFH subtype, the treatment appears to work even better with a CR rate of 88%. The one-year progression-free survival (PFS) for all patients was 66%, and for the PTCL-TFH subgroup was 70%. The one-year overall survival (OS) for all patients was 81% and PTCL-TFH patients 94%. The research team is further analyzing sequencing biomarkers to correlate with response and survival. 

This study provides the first demonstration that the addition of epigenetic hypomethylating agent oral azacitidine (CC486) to CHOP as initial therapy is safe, and highly effective to induce complete remission in PTCL. This combination will be further evaluated in the upcoming ALLIANCE/Intergroup randomized study A051902, comparing oral azacitidine-CHO(E)P with duvelisib-CHO(E)P against CHO(E)P in CD30 negative PTCL.

Abstract 40: Multi-Center Phase II Study of Oral Azacitidine (CC-486) Plus CHOP As Initial Treatment for Peripheral T-Cell Lymphoma (PTCL)

Type: Oral presentation
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Clinical Studies in T/NK Cell Lymphoma
Saturday, December 5, 2020: 7:45 AM PST

ASH 2020 Weill Cornell Medicine Lymphoma Program research coverages continues throughout the conference.

COVID-19 and Cancer: Helpful Resources for Lymphoma Patients

The Weill Cornell Medicine Lymphoma Program team remains committed to supporting and protecting the health and safety of our patient community during this challenging time. With COVID-19 dominating the news and impacting our everyday lives, many people may be left wondering which sources to trust and which recommendations to follow when it comes to understanding the coronavirus and staying safe during this unprecedented time.

We developed this article and compiled a handful of reliable resources designed to help lymphoma patients — at our center and beyond – best navigate this rapidly changing situation.

COVID-19 Basics and General Guidelines

Physicians and staff within the division of Hematology and Oncology at Weill Cornell Medicine and NewYork-Presbyterian Hospital are here to provide guidance and support to our cancer patients and their loved ones. We encourage you to review the information outlined in our COVID-19 and Cancer Guide, where we provide answers to our patient community’s most frequently asked questions. You are also welcome to call our COVID-19 hotline at (646) 697-4000 with questions at any time.

If you have COVID-19 symptoms or suspect that you have been in contact with someone with COVID-19, contact your oncologist for further instruction. If you need in-person medical attention, your doctor will advise you regarding the necessary steps and preparations to protect you and others at the facility before you arrive. Please do not visit your doctor’s office or the emergency department without first being in touch with your healthcare team.

COVID-19 and Lymphoma

In the Lymphoma Research Foundation (LRF) webinar entitled “Coronavirus and What the Lymphoma Community Needs to Know,” our own Dr. John Leonard reviews the current medical understanding and response to COVID-19 (per March 19, 2020). Dr. Leonard explains why we all must work together to “flatten the curve,” and addresses frequently asked questions surrounding immune system suppression and the coronavirus, lymphoma treatment during the pandemic, the use of masks and transmission of the disease between different groups such as children, the elderly and pets.

The LRF also created a COVID-19 fact sheet complete with prevention tips and questions to ask your oncologist. Weill Cornell Lymphoma Program Chief Dr. Peter Martin and an infectious disease specialist contributed to and medically reviewed this information.

Appointments and Video Visits

Please know that we remain dedicated to the health and wellbeing of our lymphoma community and that continuing to provide world-class cancer care for our oncology patients is important to us. As part of our mission to provide care during this unprecedented time, the Hematology & Oncology division has been implementing extensive patient-centered precautions. These include efforts to prevent the spread of COVID-19 within our facilities and the expansion of virtual video-based appointments.

The Weill Cornell Lymphoma Program continues to be able to offer new and current patients the cancer care they need. We also provide expert, multidisciplinary care for patients with lymphoma who need medical attention for COVID-19.

Video visits allow patients to receive high-quality lymphoma care from the comfort and convenience of their own homes, while adhering to safe social distancing parameters recommended to minimize exposure to other individuals. Our video visit capabilities also extend to patients who wish to schedule a virtual second opinion.

To schedule a video visit, please follow the instructions below. Our team will work with you to obtain any necessary medical records prior to your visit. We will inform you if we believe that you are better suited for an in-person visit.

New Patients
Please call (646) 962-2800.

Existing Patients
Please call (646) 962-2064.

Learn more about video visits. Once your video visit is scheduled, use this guide to connect with your doctor.

Video visits use the same insurance coverage as in-person appointments, and your copayment and deductible still apply.

Visitor Policy

While we recognize the value of family and friends’ support throughout lymphoma diagnosis and treatment, keeping patients and their loved ones safe requires temporary limits on the number of people allowed to accompany each patient to an appointment. Please note that our policies continue to evolve during these unprecedented times. Click here for our latest COVID-19 visitation guidelines.

Additional Resources

Patients are welcome to call the WCM/NYP COVID-19 hotline – (646) 697-4000 – with any questions. Please note that this hotline is available as a public service to provide information only, and not to diagnose, treat or render a medical opinion.

Patients may also consult the following resources.

Ways to Help

It can be easy to feel powerless in the midst of a global pandemic, but there are ways that you can help. In fact, the biggest impact that people – sick or healthy – can make in the fight against COVID-19 is simply to stay at home to curb the spread of disease and its potential to overwhelm the healthcare system.

Those willing and able to contribute to Weill Cornell Medicine and NewYork-Presbyterian’s response to COVID-19 can make a donation to support the purchasing of ventilators and personal protective equipment (PPE), and the physical and emotional wellbeing of healthcare workers on the frontlines of the outbreak.

A fundraiser was also created to provide nutritious, high-quality meals to the New York City doctors, nurses and ancillary staff leading the fight against COVID-19 as part of medical intensive care units.