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.

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Dr. Richard Furman, M.D.

“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.

Dr. Peter Martin On Future Treatment Options for Mantle Cell Lymphoma

In this video from OncLive, Dr. Peter Martin discusses potential changes in the future treatment of younger patients with mantle cell lymphoma (MCL), as well as new lines of therapy currently being developed for all patients with MCL. These new therapies include Bruton’s tyrosine kinase inhibitors, PI3 kinase inhibitors, Bcl-2 inhibitors, immunomodulatory drugs, and immunotherapy agents.

In the Lymphoma Program our patient care is informed by our clinical research. A full listing of available trials for MCL can be found on our clinical trials website.

Update from ASH 2011: New treatments for mantle cell lymphoma are on the horizon

By Peter Martin, MD

Update: this study is closed to enrollment. 

Arguably the most exciting news to come from the American Society of Hematology (ASH) meeting this year was the presentation by Dr. Michael Wang of preliminary results from the phase 2 trial of PCI-32765 for patients with previously treated mantle cell lymphoma (MCL). PCI-32765 is an oral (pill form) inhibitor of an enzyme called Bruton’s Tyrosine Kinase (BTK). BTK plays an important role in communicating pro-survival signals from the cell microenvironment to the nucleus of the cell. Inhibition of BTK by PCI-32765 demonstrated promise in patients with MCL in a national phase 1 that was open at Weill Cornell Medical College. This phase 2 study, also open at Weill Cornell, demonstrated a response rate of approximately 60-70% with little toxicity (mostly mild gastrointestinal side-effects). It is too early to determine how long these effects will last or whether there are any side effects that will become apparent with longer treatment. Click here for more information about this trial.

Dr. Beata Holkova presented the results of a National Cancer Institute (NCI) phase 2 study that was open at several institutions across the country, including Weill Cornell. The trial evaluated the combination of bortezomib (FDA-approved for treatment of patients with previously treated MCL) plus the histone deacetylase inhibitor vorinostat. The combination demonstrated synergistic activity in preclinical studies and showed promised in earlier trials in patients with multiple myeloma. Preliminary results from this NCI trial were encouraging, particularly in the group of patients with MCL that had never been treated with bortezomib. The trial is ongoing. Click here for more information about this study.