2021 American Society of Hematology (ASH) Annual Meeting

For the 63rd year in a row, the American Society of Hematology (ASH) hosted the Annual Meeting & Exposition. ASH is one of the world’s largest professional organizations made up of physicians and scientists with a keen interest in tackling blood diseases. This annual ASH conference is attended by approximately 25,000 participants, mainly hematology professionals, who gather to discuss the latest research and updates in topics across both malignant and non-malignant hematology. This year, members from around the world met in a hybrid – both in-person and virtual – format.

Every year, we celebrate the Weill Cornell Medicine (WCM) Lymphoma Program team members whose new discoveries and research in lymphoma are selected for presentation at the ASH meeting. Throughout the 2021 ASH conference, we covered these research updates via our Twitter feed, including perspectives and insights into original research coming out of our basic science laboratories as well as translational and clinical research studies. Dr. John Leonard shared what he found to be the top 10 most impactful and important lymphoma research abstracts as part of the #LeonardList: a yearly countdown on Twitter leading up to the annual ASH meeting which, for the fourth year in a row, has been accompanied by a CancerCast podcast episode. In this special edition of CancerCast, listeners are able to hear directly from Dr. Leonard regarding the “why” behind his #LeonardList selections, as well as gain access to 5 additional bonus podcast-only choices. Each year the Leonard List provides insight into research that is changing the treatment landscape for lymphoma patients, as well as other important issues lymphoma patients face such as financial toxicities and disparities in care. Listen to the teaser clip below for a sneak peek and tune in to CancerCast for the full episode available on Apple PodcastsGoogle PodcastsSpotify, or online at Weill Cornell Medicine.


This year’s ASH meeting heralded amazing research achievements in all sectors of hematology. Notably, within the field of lymphoma, presentations at ASH 2021 demonstrated scientific and treatment advancements that may carve the way for more targeted therapies and improved outcomes for patients. The WCM team shared research updates across many different types of lymphoma. While most abstracts dove deeply into one form of the disease, some presented on research that combined work in multiple types of lymphoma.

This research involving Dr. Richard Furman and colleagues from around the country evaluated a novel antibody-drug conjugate targeting a surface protein found in many cancers. Encouraging results were seen in the current phase I study, including high response rates in heavily relapsed and refractory mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) patients.

Here is a breakdown of some of the additional great lymphoma work that WCM physicians and researchers shared throughout the ASH 2021 meeting.


B-Cell Lymphoma

Diffuse Large B-Cell Lymphoma (DLBCL)

In collaboration with Dr. Ari Melnick’s lab, Dr. Madhav Seshadri – Chief Hematology & Oncology Fellow at Weill Cornell Medicine and NewYork-Presbyterian Hospital – presented lymphoma research which revealed a novel target and new type of agent that could ultimately lead to more treatments for DLBCL patients who have dependency on the protein MALT1.

Dr. Rossella Marullo, a 2020 ASH Scholar Award Recipient and current Instructor in Medicine at WCM, presented an oral abstract on work performed in collaboration with Dr. Leandro Cerchietti’s lab. The WCM team discovered changes in gene expression linked to aging that could explain why older lymphoma patients have a harder time tolerating certain treatments. This has important implications for the future development of therapies that may be better tolerated and result in higher cure rates for older lymphoma patients.

Work by Dr. John Leonard and colleagues from across the country as part of the National Cancer Institute (NCI) Alliance, a cooperative clinical trial group, was featured in an oral presentation. The study demonstrated the feasibility of prospective clinical trials for certain lymphoma patients, specifically two DLCBL subtypes, double hit and double expressor lymphoma. 

Dr. Coraline Mlynarczyk, a post-doctoral fellow in Dr. Ari Melnick’s laboratory and ASH 2021 Scholar Award Recipientpresented new research findings demonstrating that BTG1 mutations can lead to more aggressive B-cell lymphomas, like DLBCL. Exploiting this genetic vulnerability could ultimately lead to the creation of new targeted therapies for patients with this aggressive form of lymphoma.


Follicular Lymphoma (FL)

Weill Cornell medical student, Danny Luan, MPH, presented work conducted under the mentorship of Weill Cornell Lymphoma Program Chief Dr. Peter Martin. This retrospective analysis of follicular lymphoma clinical trials focused on expanding eligibility criteria to better reflect the population makeup of patients diagnosed with FL, allowing the results to be more generalizable outside of the clinical trial setting.


T-Cell Lymphoma

Dr. Jia Ruan presented her investigator-initiated phase 2 peripheral T-cell lymphoma clinical trial at ASH 2021. This multi-center clinical trial looked at the combination therapy of oral azacytidine (CC-486) plus CHOP, demonstrating impressive complete response (CR) rates of about 75%, which appears better than the CR rate of 40% that has historically been observed with standard CHOP alone. This combination will be further evaluated in a randomized study via the ALLIANCE/US Intergroup (A051902).


Chronic Lymphocytic Leukemia (CLL)

CLL research on a phase 3 clinical trial that Dr. Richard Furman was involved with compared two therapies, acalabrutinib and ibrutinib, for outcomes and tolerability to evaluate differences in adverse events related to long-term drug exposure in addition to cancer control. Acalabrutinib demonstrated better tolerability overall.

Dr. Richard Furman and Dr. John Allan also participated in research alongside a global team showing that certain receptor binding activities in CLL cells may explain why patients experience impairments to immune system function. This research may help to explain the underlying mechanisms behind why certain CLL treatments appear to improve immune system function.


Finally, in addition to the amazing research that our team was involved with at this year’s ASH meeting, Dr. Wendy Béguelin – an assistant professor of pharmacology at WCM – was selected to speak as an ASH Scholar Award Recipient. She presented her work during two 10-minute Blood Drop sessions with the goal of educating trainees at all levels during this ASH-a-Palooza event. Dr. Beguelin’s presentation aimed to answer the question, “What can cause lymphoma?” Throughout these sessions, Dr. Beguelin explained her research on the role of EZH2 mutations in initiating cancer predispositions for B-cell lymphomas. 


As always, we are incredibly proud of our team’s continued commitment to advancing the overall understanding of lymphoma biology, improving clinical outcomes, and enhancing the quality of life for all those affected by the disease. While this year’s ASH 21 meeting has come to a close, ongoing research continues at the WCM Lymphoma Program as our physicians and scientists work relentlessly to advance the field year-round.

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.

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.

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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.”

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