The 56th American Society of Hematology (ASH) Annual Meeting and Exposition held in San Francisco on December 6-9, 2014, brought together the best and brightest in the field of hematological disease from across the globe. More than 25,000 physicians, scientists and health professionals reported the latest clinical and scientific advancements in hematology, including discoveries in drug development, personalized therapy, and the molecular and genetic basis of blood cancers. Like years past, investigators from the University of Chicago Medicine Comprehensive Cancer Center continued their leadership and had a strong presence at the annual meeting of the world’s largest professional society dedicated to understanding, diagnosing, treating, and preventing blood diseases. The scientific program included hundreds of special symposia and scientific forums, oral and poster presentations, and comprehensive education sessions. The following is a snapshot of the research advances presented by investigators from the Comprehensive Cancer Center in all of these platforms.
Special Symposia and Scientific Forums
In the Plenary Session, Michelle Le Beau, PhD, Arthur and Marian Edelstein Professor of Medicine, director of the Comprehensive Cancer Center and a member of the ASH Executive Committee, introduced one of the very prestigious oral presentations. Le Beau provided a comprehensive overview of myelodysplastic syndrome (MDS) characterized by deletions of chromosome 5 and the current understanding and application of the immunomodulatory drug lenalidomide as an effective therapy for a talk given by student Emma Fink from Brigham and Women’s Hospital, entitled “Lenalidomide induces ubiquitination and degradation of CSNK1A1 in MDS with del(5q).” As an international leader in cancer genetics and cytogenetics, Le Beau has particular expertise in del(5q) hematological malignancies. She also moderated a session on “Spliceosome Gene Mutations in Myelodysplastic Syndromes” on the final day of the conference.
In a session on “Predisposition to Myeloid Neoplasms” organized by the ASH Scientific Committee on Myeloid Neoplasia, Jane Churpek, MD, assistant professor of medicine, provided an update of the growing field of inherited predisposition to MDS and acute leukemia. She described the increased recognition of inherited forms of MDS and acute leukemia among adult patients and discussed the genes identified thus far that are associated with subtypes of familial MDS and/or acute leukemia syndromes, including ANKRD26, CEBPA, GATA2, PAX5, RUNX1, SRP72, TERC, TERT, and TP53. Genetic testing for these abnormalities, and identification of novel genetic alterations, is critical because clinical features, although overlapping, can be unique for each syndrome and will dictate optimal care for the patient and high-risk family members. Churpek presented work being conducted by her colleagues Lucy Godley, MD, PhD, associate professor of medicine and co-leader of the Comprehensive Cancer Center Hematopoiesis and Hematological Malignancies (HHM) scientific program (as well as a member of the ASH Scientific Committee on Myeloid Neoplasia) and Sandeep Gurbuxani, MD, PhD, assistant professor of pathology, to identify a germline mutation in ANKRD26 in a family with predisposition to myeloid malignancies. Some of this work was published in the December issue of Leukemia & Lymphoma.
Career development is an important component of the ASH Annual Meeting, and there are several networking opportunities for junior investigators and trainees. Amittha Wickrema, PhD, professor of medicine, participated in a Career Development Lunch session, specifically in a roundtable discussion focused on “PhD Careers” aimed at medical students, graduate students, and residents. He shared his experience as a PhD academic researcher whose research focuses on the understanding of signaling pathways that guide lineage commitment and terminal differentiation of erythroid cells.
In a presentation that generated considerable attention by the media and conference attendees, Wendy Stock, MD, professor of medicine and co-leader of the Comprehensive Cancer Center HHM program, described results from a large, prospective United States intergroup trial, C10403, designed to test the feasibility and effectiveness of treating older adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) with the standard intensive pediatric therapeutic regimen. Stock reported significant improvements in event-free survival and overall survival for these AYA patients compared to historical controls, findings that validate this approach for the treatment of AYA with ALL. Read more about Stock’s work here at Science Life.
Results from a multicenter study led by Andrew Artz, MD, assistant professor of medicine, demonstrated the utility of using pre-transplant levels of C-reactive protein (CRP), ferritin and albumin as biomarkers for transplantation outcomes. The authors showed that elevated CRP and ferritin, and decreased albumin, prior to allogeneic hematopoietic cell transplant were associated with impaired transplant survival, primarily through higher transplant-related mortality. Once validated, it is hoped that integration of these biomarkers into clinical practice will enhance risk stratification, improve adjustment for comparative studies, and improve the design of biomarker-driven clinical trials.
The University of Chicago multiple myeloma program, led by Andrzej Jakubowiak, MD, PhD, professor of medicine, was highlighted at several talks and poster presentations at the meeting. Particularly noteworthy, interim results from ASPIRE, a randomized, open-label, multicenter phase III study were presented by Dr. Keith Stewart from the Mayo Clinic. The investigators, including Jakubowiak, demonstrated that addition of the proteasome inhibitor carfilzomib to lenalidomide and the corticosteroid dexamethasone in patients with relapsed multiple myeloma significantly improved progression-free survival and published the findings in The New England Journal of Medicine while the meeting was underway. Jakubowiak’s team also reported data demonstrating that minimal residual disease status predicts progression-free survival in newly diagnosed multiple myeloma patients treated with carfilzomib, lenolidomide, and low-dose dexamethasone, as well as results from a Multiple Myeloma Research Consortium multicenter phase Ib/II study to test carfilzomib, pomalidomide and dexamethasone in patients with lenolidomide-exposed and/or –refractory but proteasome inhibitor-naïve or –sensitive multiple myeloma. The research team was also honored at the meeting with presentation of the Multiple Myeloma Research Foundation 2014 Accelerator Award for their outstanding efforts and exceptional contributions to the rapid completion of clinical trials supported through the Multiple Myeloma Research Consortium and for their demonstrated leadership as members of the Consortium.
In several highly interactive and well-attended poster sessions, Comprehensive Cancer Center members shared the latest ground-breaking data from their research groups. Y. Lynn Wang, MD, PhD, professor of pathology, presented studies showing that the signaling molecules SYK and STAT3 are active in diffuse large B-cell lymphoma and may represent important targets for the SYK/JAK dual kinase inhibitor cerdulatinib in this disease. Chadi Nabhan, MD, associate professor of medicine, described racial variations in disease characteristics, presentation, treatment and outcomes in chronic lymphocytic leukemia (CLL) from a collaboration with investigators at the Mayo Clinic. In a second poster, Nabhan presented patterns of care of aged CLL patients in the United States. Using the Connect-CLL prospective, longitudinal, multicenter registry, the group showed that CLL patients over 75 more frequently overexpress CD38 marker, more commonly have significant co-morbidities and may more commonly demonstrate high-risk cytogenetic abnormalities, although the impact of these characteristics on outcomes will be the focus of future study.
Sonali Smith, MD, associate professor of medicine, described results from the Alliance A051201 and A051202 multicenter trials in which unexpected and serious toxicities were observed in patients with relapsed/refractory B cell lymphomas treated with a combination of idelalisib (a PI3K inhibitor), lenalidomide (an immunomodulator) and rituximab (anti-CD20 monoclonal antibody). From the groups of Yusuke Nakamura, MD, PhD, professor of medicine, and Wendy Stock, MD, fellow Houda Alachkar, PharmD, PhD, described a novel approach to identify and characterize T-cell receptor repertoires in acute myeloid leukemia patients before and after combined haploidentical and umbilical cord blood transplant. A study from Justin Kline, MD, assistant professor of medicine, and colleagues demonstrated that activation of the stimulator of interferon genes (STING) DNA sensing receptor enhances immunity and survival in a murine myeloid leukemia model.
Richard Larson, MD, professor of medicine, presented the results of a multicenter trial with long-term follow-up comparing the efficacy and safety of the tyrosine kinase inhibitors nilotinib and imatinib in patients with newly diagnosed chronic myelogenous leukemia in chronic phase (CML-CP). Larson and colleagues found that nilotinib resulted in improved efficacy compared to imatinib, including fewer patients showing disease progression and dying from advanced CML. Additionally, nilotinib was generally well tolerated and showed a positive benefit-risk profile in patients with newly diagnosed CML-CP. Larson also moderated an oral session on “Immunotherapeutic Trials in Acute Lymphoblastic Leukemia.”
For the second consecutive year, University of Chicago Committee on Cancer Biology doctoral student Colles Price in the laboratory of Jianjun Chen, PhD, assistant professor of medicine, was named as an ASH Minority Graduate Student Abstract Achievement Awardee. In his poster presentation, Price described his latest findings characterizing the polycomb group member RING1-and YY1-Binding Protein (RYBP) as a functional tumor suppressor in mixed lineage leukemia (MLL). Other work presented by Chen’s group included a poster on the identification of miR-22 as a potent inhibitor of MLL-AF9-induced transformation of mouse bone marrow progenitor cells, and that the miR-22 gene is repressed by the TET1 epigenetic regulator, as well as affected by DNA copy loss in a subset of acute myeloid leukemia cases. Chen was also a moderator of an oral session entitled “Oncogenes and Tumor Suppressor: New Players and Potential Therapeutic Targets.”