Tag: DLBCL

2022 American Society of Hematology (ASH) Annual Meeting Recap

The 2022 American Society of Hematology (ASH) Annual Meeting marked the 64th year in a row that hematology professionals gathered to discuss the latest research and updates in blood cancers and blood disorders. ASH is the world’s largest professional organizations made up of physicians and scientists with a keen interest in tackling blood diseases. Over 25,000 attendees participate in the annual ASH Meeting which aims to highlight advancements across both malignant and non-malignant hematology. Similar to last year’s meeting, ASH was hosted in a hybrid format, accommodating members from around the world to gather both virtually and in-person in New Orleans.

Each year, we look to honor and celebrate the Weill Cornell Medicine (WCM) Lymphoma Program team members whose new discoveries and research were selected for presentation at the ASH meeting. During the conference, we provided insights and perspectives via coverage on our Twitter feed, offering a deeper look into original research coming out of our basic science laboratories as well as translational and clinical research studies.

Leading up to the conference, Dr. John Leonard shared his #LeonardList: a yearly countdown on Twitter highlighting what he found to be the top 10 most impactful and important lymphoma research abstracts presented at the ASH annual meeting. For the fifth year in a row, a special CancerCast podcast episode provided listeners insight directly from Dr. Leonard regarding the “why” behind his #LeonardList selections, as well as 5 additional bonus podcast-only choices. His abstract selections aim to highlight research that is changing the treatment landscape for lymphoma patients, as well as other important issues as racial disparities and other factors in care. Listen to the teaser clip below for a sneak peek and tune into CancerCast for the full episode available on Apple Podcasts, Google Podcasts, Spotify, or online at Weill Cornell Medicine.

At this year’s ASH meeting, many of the notable presentations demonstrated scientific and treatment advancements that are leading the way for more targeted therapies and improved outcomes for patients. The WCM team shared research updates across many different forms of lymphoma.

Research involving Dr. Richard Furman investigated a novel treatment for people with lymphoma, including patients with mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and Richter’s transformation (RT). The study found that the treatment was tolerable and efficacious in well-treated and refractory patients, a population that often is less likely to respond to therapies. Dr. Furman breaks down the findings below.

The Weill Cornell Lymphoma Program is proud to partner with the Lymphoma Epidemiological Outcomes (LEO) Cohort, representing the largest, most diverse group of lymphoma patients studied to-date. At ASH 2022, our team was involved with many research updates involving this cohort. Our program chief, Dr. Peter Martin, shared his sentiments of gratitude, and our recent blog post details this LEO Cohort research.

Below is a breakdown of some of the additional great lymphoma work that Weill Cornell physicians and researchers shared throughout the ASH 2022 meeting.

Mantle Cell Lymphoma (MCL)

Dr. Jia Ruan presented data from an investigator-initiated multi-center study evaluating a triplet-combination therapy for mantle cell lymphoma (MCL) patients. In this phase II trial, the team added acalabrutinib to the doublet lenalidomide and rituximab treatment regimen with encouraging results. The study also explored minimal residual disease status as a biomarker to adjust treatment intensity and duration.

Diffuse Large B-Cell Lymphoma (DLBCL)

Dr. Mohammad Alhomoud, a current Weill Cornell Medicine and NewYork-Presbyterian Hospital Hematology & Medical Oncology fellow, participated in this year’s ASH conference. Below, he breaks down this research investigating the impact of low-dose radiation in combination with CAR T-cell therapy for diffuse large B-cell lymphoma (DLBCL).

Dr. Danny Luan presented at ASH 2022 on research he conducted under the mentorship of Weill Cornell Lymphoma Program Chief, Dr. Peter Martin, and other team members. Dr. Luan completed medical school at Weill Cornell and is now in his first-year residency at Weill Cornell and NewYork-Presbyterian Hospital. He reported on a new predictive model for DLBCL outcomes after patients complete immunochemotherapy.

Dr. Nicolás Di Siervi – a postdoctoral associate in Dr. Leandro Cerchietti’s lab –presented an oral abstract on a novel target for aggressive B-cell lymphomas. This research looked deeper into the tumor microenvironment to identify vulnerabilities that could be targeted for future lymphoma therapies.

T-Cell Lymphoma

Dr. Jia Ruan was selected to present research at this year’s ASH conference regarding how certain care factors affect clinical outcomes for peripheral T-cell lymphoma (PTCL) patients. Specifically, Dr. Ruan’s research dove into data from the Lymphoma Epidemiological Outcomes (LEO) and National Cancer Institute (NCI) supported Molecular Epidemiology Resource (MER) cohorts.

Chronic Lymphocytic Leukemia (CLL)

Dr. Richard Furman shared insights into results from a phase I/II clinical trial of acalabrutinib in relapsed and refractory chronic lymphocytic leukemia (CLL) patients. This research  provided the longest follow-up dataset to-date for this subset of CLL patients. Dr. Furman explains the significance of this research below.

Dr. John Allan presented an oral abstract based on the CAPTIVATE study highlighting four year follow-up data from the minimal residual disease (MRD) study cohort of patients with chronic lymphocytic leukemia (CLL).

Finally, in addition to the important research that our team was involved with at this year’s ASH meeting, we had a few thought leaders selected to participate in specialized programming. Dr. John Leonard Chaired a Friday Satellite Symposium session in which Dr. John Allan was a panel speaker titled “Aggressive B-Cell Lymphomas: Experts Discuss New Care Standards and Evolving Treatment Strategies.” Alongside fellow lymphoma experts, Drs. Leonard and Allan helped  educate attendees on innovative care strategies for aggressive B-cell lymphomas, including diffuse large B-cell lymphoma and mantle cell lymphoma.

Dr. Jia Ruan presented on “Fixing the Target on Aggressive Lymphoma: Insights on the Next Phase of Integrating Targeted Agents into MCL and DLBCL Management.” This CME program discussed the use of targeted agents, including new evidence with BTK inhibitors in MCL and DLBCL indicating that these therapies may lead to better treatment responses when added to established therapeutic platforms or when used in disease subtypes defined by specific molecular features.

Dr. Leandro Cerchietti also spoke at a Scientific Program on Stromal Cells in Lymphoma, highlighting the role of these specialized cells in the lymphoma tumor microenvironment. Dr. Cerchietti discussed how leveraging certain biological vulnerabilities may lead to future therapies.

The Weill Cornell Medicine Lymphoma Program remains committed 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 we are wrapping up coverage of our involvement at the 2022 ASH meeting, the WCM Lymphoma Program physicians and scientists continue to conduct research each and every day to advance the field.

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.

Precision Medicine Combination Treatment Shows Anti-Tumor Activity in Preclinical DLBCL Models

By Sucharita Mistry, PhD

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in adults. DLBCLs are aggressive and typically represent a heterogeneous collection of diseases that can be grouped into different subtypes depending on their particular genetic lesions.

One such subtype, described as the C3 or EZB cluster, features alterations in the BCL2 gene and mutations in chromatin remodeling genes such as EZH2. The malignant growth of this particular subtype of DLBCL is likely dependent on genetic abnormalities in EZH2 and BCL2. Both these oncogenes (genes with the potential to cause cancer) mediate their effects on tumor growth through distinct mechanisms, providing new opportunities for rational therapeutic strategies that inhibit EZH2 and BCL2 concurrently.

Dr. Lisa Roth and colleagues from the Weill Cornell Medicine and NewYork-Presbyterian Hospital Lymphoma Program evaluated the efficacy of EZH2 inhibitor tazemetostat and BCL2 inhibitor venetoclax as single agents and in combination using different preclinical models.

Tazemetostat and venetoclax were administered alone and in combination in a panel of DLBCL cell lines with and without mutations in EZH2 and translocation (a genetic abnormality in which a chromosome breaks and reattaches to a different chromosome) in BCL2. In DLBCL cells harboring EZH2 mutation and BCL2 translocation, the combination treatment markedly enhanced cell killing compared to either drug alone. Although these findings are encouraging, cell culture models are limited as lymphoma cells grown on a plastic surface in liquid cultures cannot recapitulate the physiologic environment within the human body.

To test the efficacy of the drugs in models with increased clinical relevance, Weill Cornell researchers established three-dimensional (3D) organoids that closely mimic the lymph node architecture in humans. The tazemetostat/venetoclax combination therapy was tested in two different novel organoid systems 1) organoids derived from lymphoma cells, and 2) patient-derived xenograft (PDX) organoids generated from a patient tumor and propagated in mice. The PDX tumor carried both EZH2 mutation and BCL2 translocation. In both types of organoids, tazemetostat and venetoclax had minimal activity as single agents, whereas the tazemetostat/venetoclax combination resulted in significant cell killing.

Using novel model systems, this study demonstrated that EZH2 inhibition combined with BCL2 inhibition results in synergistic anti-tumor effects. Learn more about the findings here.

Lisa“The synergistic anti-lymphoma activity mediated by the combination of tazemetostat and venetoclax is quite promising,” says Dr. Roth. “This combination therapy is anticipated to be especially effective as precision therapy for DLBCL patients with EZH2 mutation and BCL2 alteration.”

A clinical trial of this combination treatment is currently in development in collaboration with Drs. Ari Melnick, John Leonard and Peter Martin.