Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin's lymphoma (NHL), comprising less than 10% of all NHL diagnoses, characterized by frequent relapses and shortened survival. There are no currently available curative therapies and no standard front-line therapy exists. Initial treatment includes intensive combination chemotherapy with stem cell transplantation or less aggressive approaches with maintenance rituximab, depending on the age and performance status of the patient. Recently, ibrutinib, an oral bruton's tyrosine kinase inhibitor, has had significant activity in patients wit relapsed disease and patients have remained on the agent up to 2-years with limited toxicities. The primary aim of this proposal is to develop a specialized center for research at the Ohio State University (OSU) focused on novel therapeutics and combinations with ibrutinib in MCL and to train new investigators in the field. Dr. Blum has mentored multiple trainees over the past five years; however, training opportunities and funding for lymphoma clinical research is limited and insufficient to address the clinical challenges of drug development in MCL and other NHL subtypes. This award will support Dr. Blum's efforts to develop a clinical research training program designed to support and train junior faculty, hematology/oncology fellows, residents, and medical students at OSU and nationally in the complexities of superior clinical research. The primary aims of this specialized research program include all of the following: 1. To explore novel therapeutic combinations with ibrutinib (including combinations with lenalidomide, palbociclib, KPT-330, and rituximab and bendamustine) as therapy for patients with newly diagnosed or recurrent MCL, 2. To evaluate other novel agents in the B-cell receptor signaling and similar pathways (including BKM120, LEE011, and MLN8237) in patients with ibrutinib resistant MCL, and 3. To develop an institutional and national clinical research mentoring program in clinical investigation in B-cell malignancies.
Aims 1 -3 (50% of Dr. Blum's efforts) will serve to develop the careers of junior faculty, fellows, and residents at OSU and within the United States committed to clinical research in lymphoma through mentoring programs conducted at OSU, through the American Society of Hematology, and through the Lymphoma Research Foundation. Ultimately, with Dr. Blum's mentorship in the conduct of these trials with ibrutinib and other novel agents, it is anticipated that several of these trainees will become independent investigators in the field of NHL therapeutics that not only have a track record of publication, but also have career development funding including NCI K23 and foundation grants to support their research.
Mantle cell lymphoma is a type of non-Hodgkin's lymphoma with an aggressive clinical presentation and frequent relapses. Dr. Blum is a clinical investigator with established expertise in novel therapeutics for mantle cell lymphoma including a recently published paper in the New England Journal of Medicine that demonstrates significant activity with ibrutinib, an oral bruton's tyrosine kinase inhibitor, in patients with recurrent mantle cell lymphoma. She proposes to develop a comprehensive clinical research program for mantle cell lymphoma designed to test new combination approaches with ibrutinib, to discover new therapies for mantle cell lymphoma, and to train the next generation of investigators in the field.
