Tag: American Society of Hematology

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 Podcasts, Google Podcasts, Spotify, 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 Recipient, presented 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.

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.
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