chronic lymphocytic leukemia – New Developments in Lymphoma

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).

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.

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

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.

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.

2018 American Society of Clinical Oncology (ASCO) Annual Meeting

The American Society of Clinical Oncology (ASCO) is the world’s leading organization for physicians and oncology professionals who care for people with cancer. Each year, ASCO’s Annual Meeting brings together over 30,000 oncology professionals from around the world to discuss state-of-the-art treatment modalities, new therapies and ongoing controversies in the field.

Our Lymphoma Program is proud to have been part of several research studies presented at this year’s meeting, contributing to new discoveries across a range of lymphoma subtypes. Here are the latest updates from our team:

T-Cell Lymphoma

An unmet treatment need exists for peripheral T-cell lymphoma patients, especially those with relapsed/refractory disease. Dr. Jia Ruan was part of a research team testing immunotherapy agent pembrolizumab within this patient population.

Follicular Lymphoma

Dr. Peter Martin was involved in a clinical trial investigation of acalabrutinib in treatment of follicular lymphoma, which yielded promising response rates.

Data supporting vitamin D supplementation in indolent lymphoma patients treated with rituximab were presented at this year’s meeting. Dr. John Leonard is Weill Cornell Medicine and NewYork-Presbyterian’s principal investigator evaluating the vitamin’s effects in an ongoing phase III trial. Trial information here.

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Diffuse Large B-Cell Lymphoma (DLBCL)

Dr. Jia Ruan was involved in the clinical trial assessment of single-agent acalabrutinib in relapsed/refractory DLBCL patients.

Waldenstrom’s Macroglobulinemia

Dr. Richard Furman was senior author on a study demonstrating acalabrutinib as an effective and well-tolerated therapy for people with Waldenstrom’s macroglobulinemia.

Chronic Lymphocytic Leukemia (CLL)

Dr. John Allan, along with Dr. Richard Furman, collaborated with research colleagues to investigate the demographic impact on incidence and treatment outcomes in people with chronic lymphocytic leukemia (CLL).

Dr. John Allan is Weill Cornell Medicine and NewYork-Presbyterian’s principal investigator for a phase II clinical trial of ibrutinib and venetoclax – two non-chemotherapeutic agents – in people with previously untreated chronic lymphocytic leukemia (CLL). Trial information here.

Non-Hodgkin Lymphoma

People with human immunodeficiency virus (HIV) are at increased risk for developing aggressive non-Hodgkin lymphomas frequently associated with two herpes viruses: Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpes virus (KSHV). Weill Cornell Medicine pathologist Ethel Cesarman, MD, PhD, contributed to a phase II trial conducted through the AIDS Malignancy Consortium (AMC) to test HDAC inhibitor vorinostat’s effects on HIV-related non-Hodgkin lymphoma.

Dr. Peter Martin, the Principal Investigator for the Lymphoma Epidemiology of Outcomes (LEO) consortium at Weill Cornell Medicine and NewYork-Presbyterian Hospital, aided in a study of vulnerability to undesirable outcomes in people with newly diagnosed non-Hodgkin lymphoma. Vulnerable status was measured overall, and by age, gender and clinical features.

As always, we are proud of our team’s active commitment to advancing the overall understanding of lymphoma and improving clinical outcomes and quality of life for all those affected by the disease.

Ibrutinib Continues to Demonstrate Viability in Treatment of CLL

Based on the results of the first in-human clinical trial of ibrutinib in chronic lymphocytic leukemia (CLL) – conducted in 2010 at Weill Cornell Medicine/NewYork-Presbyterian Hospital and other centers – researchers led in part by Dr. Richard Furman moved forward with the first phase II trial of the drug. According to a five-year follow-up study recently published in the American Society of Hematology’s Blood journal, ibrutinib continues to demonstrate excellent efficacy and tolerability as a single agent therapy for people with previously untreated and relapsed or refractory CLL.

CLL is characterized by uncontrolled growth of mature B-cells that accumulate in the blood, bone marrow, lymph nodes and spleen. As CLL cells fill these various organs, they interfere with normal cell functions. Ibrutinib is an oral treatment that inhibits Bruton’s tyrosine kinase (BTK), an enzyme involved in B-cell development that plays a critical role in CLL cell survival.

Prior to the Food and Drug Administration (FDA) approval of ibrutinib for CLL in 2014, chemoimmunotherapy (CIT), typically with fludarabine, cyclophosphamide and rituximab (FCR), was one of the only treatment options available for people with CLL. Chemoimmunotherapy often generates deep responses that last a median of five to six years, but it is associated with significant toxicities. When patients relapse after CIT, their disease becomes more resistant to subsequent treatments, and due to the accumulation of toxicities, many patients are unable to receive further CIT. Given the associated toxicities, the use of CIT is limited in older patients with comorbidities – the cohort that comprises the majority of CLL patients.

The phase II study in which Dr. Furman was involved tested ibrutinib as a single agent in over 100 patients – some of whom received no prior therapy, and others who relapsed following initial treatment. Patients received daily oral doses of ibrutinib until their disease progressed or until the presence of side-effects warranted discontinuation of therapy.

Almost 90 percent of all patient participants demonstrated a response to treatment at the five-year mark, and complete remission rates increased over time with ongoing treatment. Ninety-two percent of treatment-naive patients and 44 percent of relapsed/refractory patients remained free of disease progression five years out from the start of treatment.

Side-effects, including infections, diarrhea, bleeding and low-blood counts, were mild. They did not prevent patients from remaining on treatment long-term and often improved with continued dosing.

“These data demonstrate the excellent long-term outcomes for CLL patients treated with ibrutinib, especially those who receive ibrutinib as their first therapy,” says Dr. Furman.

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