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.

 

2018 American Society of Clinical Oncology (ASCO) Annual Meeting

The American Society of Clinical Oncology (ASCO) is the world’s leading organization for physicians and oncology professionals who care for people with cancer. Each year, ASCO’s Annual Meeting brings together over 30,000 oncology professionals from around the world to discuss state-of-the-art treatment modalities, new therapies and ongoing controversies in the field.

Our Lymphoma Program is proud to have been part of several research studies presented at this year’s meeting, contributing to new discoveries across a range of lymphoma subtypes. Here are the latest updates from our team:


T-Cell Lymphoma

An unmet treatment need exists for peripheral T-cell lymphoma patients, especially those with relapsed/refractory disease. Dr. Jia Ruan was part of a research team testing immunotherapy agent pembrolizumab within this patient population.

ASCO18_Ruan1.jpg


Follicular Lymphoma

Dr. Peter Martin was involved in a clinical trial investigation of acalabrutinib in treatment of follicular lymphoma, which yielded promising response rates.

ASCO18_Martin2.jpg

Data supporting vitamin D supplementation in indolent lymphoma patients treated with rituximab were presented at this year’s meeting. Dr. John Leonard is Weill Cornell Medicine and NewYork-Presbyterian’s principal investigator evaluating the vitamin’s effects in an ongoing phase III trial. Trial information here.

ASCO18_Leonard

Diffuse Large B-Cell Lymphoma (DLBCL) 

Dr. Jia Ruan was involved in the clinical trial assessment of single-agent acalabrutinib in relapsed/refractory DLBCL patients.

ASCO18_Ruan2.jpg

Waldenstrom’s Macroglobulinemia

Dr. Richard Furman was senior author on a study demonstrating acalabrutinib as an effective and well-tolerated therapy for people with Waldenstrom’s macroglobulinemia.

DexwS8gVMAcoL9H.jpg

Chronic Lymphocytic Leukemia (CLL)  

Dr. John Allan, along with Dr. Richard Furman, collaborated with research colleagues to investigate the demographic impact on incidence and treatment outcomes in people with chronic lymphocytic leukemia (CLL).

Det1qwlX0AAATLa.jpg

Dr. John Allan is Weill Cornell Medicine and NewYork-Presbyterian’s principal investigator for a phase II clinical trial of ibrutinib and venetoclax – two non-chemotherapeutic agents – in people with previously untreated chronic lymphocytic leukemia (CLL). Trial information here.

DeyfOBnUYAAT8Xx.jpg

Non-Hodgkin Lymphoma

People with human immunodeficiency virus (HIV) are at increased risk for developing aggressive non-Hodgkin lymphomas frequently associated with two herpes viruses: Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpes virus (KSHV). Weill Cornell Medicine pathologist Ethel Cesarman, MD, PhD, contributed to a phase II trial conducted through the AIDS Malignancy Consortium (AMC) to test HDAC inhibitor vorinostat’s effects on HIV-related non-Hodgkin lymphoma.

ASCO18_Cesarman.jpg

Dr. Peter Martin, the Principal Investigator for the Lymphoma Epidemiology of Outcomes (LEO) consortium at Weill Cornell Medicine and NewYork-Presbyterian Hospital, aided in a study of vulnerability to undesirable outcomes in people with newly diagnosed non-Hodgkin lymphoma. Vulnerable status was measured overall, and by age, gender and clinical features.

DetLVGtW0AIqj8j.jpg


As always, we are proud of our team’s active commitment to advancing the overall understanding of lymphoma and improving clinical outcomes and quality of life for all those affected by the disease.

 

Dr. Jia Ruan and Colleagues Encouraged by Long-Term Results of Chemo-Free MCL Treatment Regimen

Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma that occurs primarily in older adults. The disease is typically managed in the initial treatment setting with a combination of chemotherapy and immunotherapy, which tends not to be curative and may impart toxic side effects in some patients.

In search of an effective, less toxic treatment option for those afflicted by MCL, Dr. Jia Ruan and colleagues explored an alternative regimen free of conventional chemotherapy – lenalidomide plus rituximab – to be used in the initial treatment setting. Their multi-center phase II clinical trial of the novel biological pairing was the first-ever study of a non-chemotherapy first-line MCL treatment approach.

Thirty-eight MCL patients enrolled in the trial from July 2011 to April 2014. They received lenalidomide on days 1-21 of a 28-day cycle, and rituximab was administered four times per week during the first cycle, then once every other cycle. The first 12-cycle treatment was considered induction, or initial therapy, and was followed by a maintenance phase, in which therapy is provided to prevent relapse. Treatment was continuous until disease progression, and patients had the option to cease therapy after three years if in remission.

At the 2017 American Society of Hematology Annual Meeting, the researchers examined the long-term outcomes of the trial in a 5-year follow-up analysis to reveal that the drug combination shows promise for effective management of MCL, with the majority of trial participants doing well and maintaining good quality of life. About 90 percent of patients responded to the therapy, and over 60 percent remain in remission.

The research team also measured minimal residual disease (MRD) in patients’ blood, the small number of cancer cells that may be left after treatment that have the potential to grow and cause the patient to relapse. In the small subset of patients with available tumor tissues for MRD analysis, about 80 percent of patients were found to be MRD negative, further demonstrating the novel treatment regimen’s activity and feasibility as an additional therapeutic option for people with MCL.

Picture2
Dr. Jia Ruan

“We are encouraged by the quality and durability of the responses with the biologic doublet of lenalidomide plus rituximab as initial therapy for mantle cell lymphoma,” said Dr. Ruan. “We hope to bring this active combination to larger studies where it can be combined with other agents and compared to conventional chemotherapy.”