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Ibrutinib is Effective Therapy for Relapsed CLL Patients

Reporting results in the New England Journal of Medicine, Weill Cornell’s Dr. Richard Furman and others recently completed a large phase 1b/2 clinical trial on the effects of ibrutinib in patients with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL). Recently granted a third breakthrough therapy designation as a monotherapy for CLL and SLL, ibrutinib acts as an oral, irreversible inhibitor of the enzyme, Bruton tyrosine kinase (BTK).  BTK is an essential component of the B-cell receptor signaling pathway and  facilitates interactions between the CLL cells and their micro-environment, promoting the survival of CLL/SLL cells.

In the clinical study, ibrutinib was administered orally to 85 previously treated patients with CLL once daily at doses of 420 mg and 840 mg. Both doses demonstrated an overall response rate of 71%, with an additional 20% and 15% in each group achieving a partial response with lymphocytosis. At a median follow up of 26 months, estimated progression-free and overall survival for the 85 patients overall were 75% and 83% respectively. Side effects were mild and included diarrhea, fatigue, and infections. The study concluded that ibrutinib produces, “a high frequency of durable remissions for relapsed or refractory CLL/SLL, including those patients with high-risk genetic lesions.”

Ibrutinib represents an important improvement in the treatment of patients with CLL/SLL.  Treatment previously consisted of regimens utilizing chemotherapies, including chlorambucil, cyclophosphamide, fludarabine, and bendamustine in various combinations that effectively generated responses in patients, but with significant toxicities.  Ultimately, patients relapsed and became unresponsive to or unable to tolerate chemotherapy.  Additionally, the subset of patients characterized by having del 17p13.1  who respond extremely poorly to chemoimmunotherapy, demonstrated response rates equivalent to the rest of the patient population.

Currently there are ongoing trials of ibrutinib in CLL and other lymphomas at the Weill Cornell CLL Research Center and Lymphoma Program. Additional clinical trials are available here.

ICML Update: Preliminary Results From a Phase I Trial of Palbociclib (PD 0332991) plus Bortezomib in Patients with Previously Treated Mantle Cell Lymphoma

Recently, at the 12th International Conference on Malignant Lymphoma, Dr. Peter Martin, presented preliminary results from a phase I study evaluating palbociclib (also known as PD 0332991) combined with bortezomib in patients with previously treated mantle cell lymphoma. Mantle cell lymphoma is characterized by genetic changes that result in loss of cell cycle control, resulting in unrestrained cell proliferation. Palbociclib is an oral drug that specifically inhibits CDK4, enzyme that is central to the proliferation of mantle cell lymphoma cells. Data from WCMC demonstrated that palbociclib could arrest the growth of mantle cell lymphoma cells and that prolonged growth arrest could sensitize the cells to killing by low doses of bortezomib, thereby potentially improving its efficacy and tolerability. In our recent oral presentation at the ICML, we reported that palbociclib could be safely combined with low-dose bortezomib and that the combination appeared to have promising efficacy. Our results suggest that strategies to control the cell cycle should be explored.

For a full listing of all current clinical trials underway in the Lymphoma Program, please click here.