Tag: John Leonard MD

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.

ASCO 2021 – Lymphoma Updates

The American Society of Clinical Oncology (ASCO) is the world’s leading organization for physicians and oncology professionals caring for people with cancer. The 2021 Annual Meeting was hosted virtually, connecting oncology professionals from around the world to discuss the newest, state-of-the-art research and treatment updates.

The Weill Cornell Lymphoma Program team is always proud of our contributions to new lymphoma research presentations at the ASCO Annual Meeting. We’ve outlined some of the highlights from this year’s conference, including research updates and new discoveries from our team. Additionally, our Weill Cornell Medicine and NewYork-Presbyterian Hematology & Oncology Fellow Dr. Sam Yamshon received a prestigious ASCO Conquer Cancer Foundation 2021 Young Investigator Award to support critical lymphoma research and the transition from fellowship to faculty. 

Samuel Yamshon, MD – 2021 ASCO Young Investigator Award Recipient

Weill Cornell Lymphoma Program Chief Dr. Peter Martin presented new mantle cell lymphoma research and shared important insights about care in the community or real-world setting as part of an oral abstract session. 

Dr. John Leonard reviews an National Cancer Institute (NCI)-supported clinical trial evaluating the role of stem cell transplant in primary central nervous system (CNS) lymphoma treatment. 

Dr. Richard Furman explains exciting results from a phase 3 clinical trial comparing two different treatment options for patients with chronic lymphocytic leukemia (CLL) for the first time.

Additionally, Dr. Peter Martin breaks down mantle cell lymphoma research evaluating the role of botezomib when added to bendamustine and rituximab as induction therapy.

PET scan imaging during treatment for bulky Hodgkin lymphoma can provide critical information to shape the course of care. Dr. John Leonard breaks down this NCI-supported ALLIANCE research presented this year’s ASCO meeting. 

Our Team’s Take on the Most Influential ASH 2018 Lymphoma Research

At the end of each year, the American Society of Hematology (ASH) Annual Meeting & Exposition brings together over 25,000 hematology professionals from around the world to discuss the latest research into the treatment of blood diseases. Highlights of ASH is a two-day program designed to update clinicians and researchers unable to attend the Annual Meeting with the findings most likely to impact daily clinical practice.

Our Lymphoma Program Chief, Dr. Peter Martin was selected to represent the Highlights of ASH Lymphoma Committee for a post-meeting update in January 2019. Here’s his take on the latest lymphoma research.

Diffuse Large B-Cell Lymphoma (DLBCL)

According to the FLYER study, patients younger than 60 with low-risk diffuse large B-cell lymphoma (DLBCL) had excellent outcomes with a shortened regimen of four cycles of R-CHOP chemotherapy versus the standard six cycles. The reduction in chemotherapy may allow for minimizing potential toxic side effects for this patient population.

Our Team’s Take
It is now clear that most young people with stage 1, low-risk DLBCL can be effectively treated with just four cycles of R-CHOP, but providers should use caution in extrapolating these results to rarer subtypes of DLBCL (e.g., primary mediastinal B-cell lymphoma, transformed lymphomas, etc.) that may not have been included in large numbers in the FLYER trial.

SOURCE 781- Excellent Outcome of Young Patients (18-60 years) with Favourable-Prognosis Diffuse Large B-Cell Lymphoma (DLBCL) Treated with 4 Cycles CHOP Plus 6 Applications of Rituximab: Results of the 592 Patients of the Flyer Trial of the Dshnhl/GLA

R-CHOP chemotherapy is the standard treatment for people with previously untreated DLBCL. The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has shown activity in people with a subtype of DLBCL known as non-germinal center B cell DLBCL (non-GCB DLBCL) whose disease has relapsed following treatment. The phase III PHOENIX trial examined whether adding ibrutinib to R-CHOP would improve treatment efficacy in previously untreated non-GCB DLBCL patients. Results demonstrated that R-CHOP plus ibrutinib was equivalent to R-CHOP alone. The study did note, however, that ibrutinib may provide some benefit in patients older than 60.

Our Team’s Take
For now, R-CHOP remains the gold-standard for most people with DLBCL, including non-GCB DLBCL. That said, it appears that BTK inhibitors have the potential to improve outcomes if the optimal patient population can be identified.

SOURCE 784 – A Global, Randomized, Placebo-Controlled, Phase 3 Study of Ibrutinib Plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (RCHOP) in Patients with Previously Untreated Non-Germinal Center B-Cell-like (GCB) Diffuse Large B-Cell Lymphoma (DLBCL)

Follicular Lymphoma

Our own Dr. John Leonard led the global phase III AUGMENT clinical trial comparing the efficacy and safety of combined lenalidomide plus rituximab versus rituximab alone in people with previously treated indolent lymphoma, including follicular and marginal zone lymphoma. Lenalidomide-rituximab treatment resulted in superior progression-free survival (PFS) and overall survival (OS) outcomes when compared to rituximab treatment alone, representing an important new treatment option for this patient population.

Our Team’s Take
The impressive overall survival benefit seen in the AUGMENT trial implies that single-agent rituximab may no longer be appropriate for some people with previously treated follicular lymphoma.

SOURCE 445 – AUGMENT: A Phase III Randomized Study of Lenalidomide Plus Rituximab (R2) Vs Rituximab/Placebo in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma

Hodgkin Lymphoma

A currently accepted standard of care treatment for early-stage low-risk Hodgkin lymphoma is two cycles of ABVD chemotherapy followed by radiotherapy. In the HD16 trial examining the possibility of omitting radiotherapy from the treatment regimen, investigators found that two cycles of ABVD alone does not provide adequate disease control.

Our Team’s Take
A primary goal of cancer care is to deliver a maximally effective treatment regimen while sparing patients from excessive treatment-related side effects. Yet, this research demonstrates that two cycles of ABVD alone does not provide sufficient control of early-stage, favorable risk classical Hodgkin lymphoma. Outside of clinical trials, providers should consider either the addition of radiation or additional chemotherapy.

SOURCE 925 – PET-Guided Treatment of Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase 3 Trial HD16 By the German Hodgkin Study Group)

T-Cell Lymphoma

Following the positive results of a phase I trial combining brentuximab vedotin (BV) with CHP (CHOP chemotherapy minus vincristine) in frontline treatment of T-cell lymphoma, researchers tested the combination in patients with newly diagnosed CD30+ anaplastic large cell lymphoma (ALCL), a type of T-cell lymphoma, in the ECHELON-2 trial. Brentuximab vedotin plus CHP was shown to produce better outcomes than standard CHOP for these patients.

Our Team’s Take
BV-CHP represents a new standard of care for anaplastic large cell lymphoma (ALK-positive and ALK-negative). It is less clear that BV adds significantly to CHOP in non-ALCL T-cell lymphomas regardless of CD30 status.

SOURCE 997 – The ECHELON-2 Trial: Results of a Randomized, Double-Blind, Active-Controlled Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in the Frontline Treatment of Patients with CD30+ Peripheral T-Cell Lymphomas

BONUS: Chimeric Antigen Receptor (CAR) T Cell Update

Multiple observational studies suggested that commercial, FDA-approved CAR T cell products used as part of standard practice resulted in outcomes that were comparable to outcomes seen in clinical trials prior to the approval of CAR T cells. Even patients with characteristics that might have resulted in exclusion from clinical trials (e.g., low blood counts) appeared to have comparable outcomes.

Our Team’s Take
CAR T cells clearly have a role in people with treatment-refractory DLBCL. Nonetheless, more research will be required to further improve the efficacy and safety of CAR T cells so that patients outside of academic medical centers might have access to this new treatment approach.

SOURCE 91 – Axicabtagene Ciloleucel (Axi-cel) CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma: Real World Experience; 92 – Axicabtagene Ciloleucel in the Real World: Outcomes and Predictors of Response, Resistance and Toxicity

 

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