Tag: Richard Furman MD

2018 American Society of Hematology (ASH) Annual Meeting

The American Society of Hematology (ASH) is the world’s largest professional society serving clinicians and scientists who work to conquer blood diseases. The ASH Annual Meeting & Exposition brings together over 25,000 hematology professionals from around the world to discuss the understanding, diagnosis, treatment, and prevention of disorders affecting the blood, bone marrow, and immunologic, hemostatic and vascular systems.

This year, the ASH Meeting celebrated its 60th anniversary in San Diego, CA. As always, our team was proud to contribute new lymphoma discoveries for presentation at the meeting. Here are some research highlights from our team.

Dr. John Leonard led a global phase III 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. Results demonstrating lenalidomide-rituximab as an important new treatment option for this patient population.

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Dr. Richard Furman and colleagues found that at follow-up of up to seven years, ibrutinib demonstrated sustained activity in both first line and relapsed/refractory chronic lymphocytic leukemia (CLL) patients.

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Dr. Peter Martin led a study examining the safety and efficacy of CC-486, also known as oral azacitidine, plus R-CHOP chemotherapy in people with diffuse large B-cell lymphoma (DLBCL).

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Using a combination of human, animal, and cell line data, Jude Phillip, PhD, of the Leandro Cerchietti Research Lab, and colleagues found that the internal architecture of lymphomas present important insights into disease progression.

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Dr. John Allan presented a preliminary update of an ongoing first-in-human study of vecabrutinib in patients with advanced B-cell malignancies.

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Dr. Sarah Rutherford reported data that may support the elimination of bone marrow biopsies in follicular lymphoma and diffuse large B-cell lymphoma clinical trials.

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Dr. Richard Furman and colleagues found that venetoclax is well tolerated and produces high levels of response in previously treated Waldenstrom’s macroglobulinemia patients.

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We are proud of our team’s continued commitment to advancing the overall understanding of lymphoma and improving clinical outcomes and quality of life for all those affected by the disease.

Dr. Richard Furman Examines Future of CLL Risk Assessment

At OncLive’s State of the Science Summit on Hematologic Malignancies, Dr. Richard Furman, director of the Chronic Lymphocytic Leukemia (CLL) Research Center at Weill Cornell Medicine, discussed how medical oncologists should be using prognostic markers to make risk assessments in order to determine individualized treatments for their patients with CLL.

SOSS_Richard_FurmanDr. Furman noted that current CLL therapies are effective, but they often lead to complications. CLL patients treated with standard chemotherapy drug combination fludarabine, cyclophosphamide, rituximab (FCR) are often prone to developing treatment resistance or Richter’s transformations (RT), in which their CLL transforms into a more aggressive diffuse large B-cell lymphoma (DLBCL). They may also succumb to infectious complications, adverse events, or secondary malignancies.

Because of the risks associated with FCR treatment, Dr. Furman suggested a movement toward treatment agents that are not as toxic, such as ibrutinib. But even with ibrutinib, patients can develop resistance to treatment. For example, in cysteine481-to-serine mutations, the amino acid in Bruton’s tyrosine kinase (BTK) that ibrutinib binds to is changed from a cysteine to a serine, prohibiting ibrutinib from continuing to bind. This results in inadequate ibrutinib coverage and enables CLL cells to escape treatment and survive.

According to Dr. Furman, a large number of CLL patients will have excellent responses and enjoy very long progression free survivals. What is important is to identify those who will not and to devise a treatment strategy that can improve their outcomes. Currently, interphase FISH (demonstrating deletion 11q or 17p), NOTCH1 mutation, or certain V genes help identify those patients who will progress on currently novel agents or have a risk of Richter’s transformation. In the future, stimulated karyotyping, or evaluating changes in the chromosomes after stimulation of the CLL cells, will also be of great importance.

The CLL team at Weill Cornell Medicine and NewYork-Presbyterian is currently investigating an early intervention trial in which patients at risk of developing Richter’s transformation or resistance to BTK inhibitors receive intervention before the mutations have a chance to develop. Our team is also looking into the use of combination therapies, such as ibrutinib and venetoclax, in treatment of CLL patients.

Additionally, Dr. Furman pointed out that prognostic markers are dependent upon the setting in which they’re used. Those used for FCR, such as minimal residual disease (MRD), don’t necessarily apply to ibrutinib. He said that prognostic markers are traditionally based upon responses, but we now need to start looking at them from a progression-free survival (PFS) perspective.

To hear more from Dr. Furman about the outlook of CLL prognostic markers, check out this short OncLive clip:

Venetoclax for CLL Patients Who are Relapsed/Refractory to Ibrutinib or Idelalisib

Furman FaceBy Richard Furman, M.D. 

Patients with CLL who relapse after or become refractory to treatments like ibrutinib or idelalisib have poor outcomes. Venetoclax (also known as ABT-199) is an oral inhibitor of the BCL-2 (B-cell lymphoma 2) protein. The BCL-2 protein plays a critical role in preventing cells from undergoing apoptosis (cell death), in healthy cells and in CLL cells. In a recent study presented at the 2016 annual ASH meeting, we evaluated the effectiveness of venetoclax in treating people who relapsed after or were refractory to ibrutinib or idelalisib.

During this phase 2 trial 64 people with CLL were divided into two arms. The first arm consisted of those who were relapsed or refractory to ibrutinib, while the second arm included those who were relapsed or refractory to idelalisib. 43 patients were enrolled in the first arm and were on ibrutinib for a median of 17 months, receiving venetoclax for a median of 13 months, while 21 patients in the second arm were on idelalisib for a median of 8 months and received venetoclax for a median of 9 months. Thirty-nine patients in the ibrutinib arm and 21 patients in idelalisib arm completed the full course of treatment. The objective response rate as determined by investigators was 69% (27/39) for people who were ibrutinib resistant, and 57% (12/21) for the idelalisib resistant. At the time of analysis no median progression free survival or overall survival has been reached. Overall the progression free survival was 72% and overall survival was 90% for all participants.

The results from this trial demonstrate that venetoclax has displayed robust activity and is tolerable for people whose CLL has progressed after treatment with ibrutinib and idelalisib. Although there have been few complete responses, patients will continue to be monitored to chart any further improvements. Additional follow up will be required to assess how long lasting venetoclax responses will be.

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