Co-Leader: Rosa Lapalombella, PhD
Co-Leader: Jennifer Woyach, MD
Co-Leader: Alice S. Mims, MD
The LHM program provides leadership in understanding the genetics and epigenetics of leukemia, discovering novel prognostic biomarkers and developing novel small molecules and immune therapeutic strategies for the treatment of leukemia.
Below are few of the most significant program accomplishments over the past five years that can be credited entirely or in part to LHM investigators:
- Performed the initial pre-clinical studies of the Bruton Tyrosine Kinase (BTK) inhibitor ibrutinib in CLL, followed by translation through Phase 1, 2, and 3 clinical trials that led to its FDA approval and a treatment paradigm change in CLL replacing chemoimmunotherapy with ibrutinib.
- Performed initial preclinical and subsequently led clinical development of a second BTK inhibitor acalabrutinib in CLL leading to recent (2019) FDA approval.
- Performed preclinical work with ibrutinib as a therapeutic agent for chronic graft versus host disease (cGVHD), which ultimately justified the trials for its eventual FDA approval for this indication.
- Contributed to the initiation of the Leukemia and Lymphoma Society (LLS) Beat AML precision medicine study (founding member) that showed improved overall survival for patients assigned to targeted therapy versus standard therapy.
- Pioneered NK cell therapy for AML that is now moving forward as part of a large NCI-sponsored clinical trial led by The Ohio State University.
LHM Cancer Focus
- Acute myeloid leukemia (AML)
- Chronic lymphocytic leukemia (CLL)
- Hairy cell leukemia (HCL)
- Adult T-cell leukemia (ATL)
- Adult and pediatric leukemia
About LHM Members
Program members include some of nation’s foremost authorities on science-based treatments for leukemia in its many forms. Their accomplishments over the past several years have elevated leukemia research at Ohio State to international renown. The program has 57 members, from seven Departments and four Colleges across The Ohio State University.
The LHM Program is led by Jennifer Woyach, MD. Dr. Woyach is an NCI-funded physician-scientist whose career has focused on CLL, immune therapy and early drug development in leukemia.
During 2015-2020, LHM Program members have published 702 manuscripts of which 23 percent are inter-programmatic, 33 percent are intraprogrammatic, 77 percent are multi-institutional, and many fall within each of these categories, bringing our total collaborative publications to 88 percent, with 164 published in journals having an impact factor >10.
In the last five years, members of LHM have accrued 1,582 patients to interventional (1,556 were therapeutic interventional) and 7,253 patients to non-interventional trials. Of the enrolled therapeutic trial patients, 1,343 (86 percent) were to Phase 1/2 trials. During this period, two drugs were FDA approved for CLL and one for chronic GVHD based upon research performed by LHM members. Additionally, LHM members are active leaders in the LLS Beat AML Precision Medicine Study for AML and MDS, the Alliance for Clinical Trials in Oncology (Alliance) and the BMT-CTN.
Key Program Objectives
Aim 1: To explore and integrate genetic, epigenetic, non-coding RNAs and immunosuppressive features of leukemic cells in order to enhance risk stratification and target identification.
Aim 2: To foster preclinical and clinical development of epigenetic, targeted and immunologic therapeutics directed at the causes of leukemic transformation and its progression, and to develop new curative therapies.
Scientific Accomplishments
Ibrutinib Regimens Versus Chemoimmunotherapy in Older Patients With Untreated CLL. Among older patients with untreated CLL, treatment with ibrutinib was superior to treatment with bendamustine plus rituximab with regard to progression-free survival. Published in The New England Journal of Medicine.
PIs: Jennifer Woyach, MD; Nyla Heerema, PhD; Gerard Lozanski, MD; James S Blachly, MD
Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. In this study, the selective BTK inhibitor acalabrutinib had promising safety and efficacy profiles in patients with relapsed CLL, including those with chromosome 17p13.1 deletion. Published in The New England Journal of Medicine.
PIs: Jennifer Woyach, MD
Midostaurin Plus Chemotherapy for Acute Myeloid Leukemia With a FLT3 Mutation. The addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event-free survival among patients with AML and a FLT3 mutation. Published in The New England Journal of Medicine.
PIs: Clara Bloomfield, MD
Acute Myeloid Leukemia. Recent advances in the disease classification, understanding of the genomic landscape, identification of prognostic factors, current treatment and new therapies under investigation in types of adult AML other than acute promyelocytic leukemia. Published in The New England Journal of Medicine.
PIs: Clara Bloomfield, MD
Time-to-Progression After Font-Line Fludarabine, Cyclophosphamide and Rituximab Chemoimmunotherapy for Chronic Lymphocytic Leukaemia: A Retrospective, Multicohort Study. The study developed a robust, reproducible 17-gene signature that identifies a subset of treatment-naive patients with IGHV-unmutated chronic lymphocytic leukaemia who might substantially benefit from treatment with FCR chemoimmunotherapy. Published in The Lancet Oncology.
PIs: Kevin Coombes, PhD; Christopher Oakes, PhD; Lynne Abruzzo MD, PhD
Venetoclax for Chronic Lymphocytic Leukaemia Progressing After Ibrutinib: An Interim Analysis of a Multicentre, Open-Label, Phase 2 Trial. The results of this interim analysis show that venetoclax has durable clinical activity and favourable tolerability in patients with relapsed or refractory chronic lymphocytic leukemia whose disease progressed during or after discontinutation of ibrutinib therapy. Published in The Lancet Oncology.
PIs: Jennifer Woyach, MD
Future Directions
- Immuno-Oncology
- Enhance research to decrease the leukemia burden in the catchment area through translational genomics, prevention and survivorship
- Define genomic groups for personalized medicine and acute intervention based upon minimal residual disease (MRD) status
- Further enhancement of collaborations
- Planned recruitments