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NCCN Annual Congress Explores Hot Topics in Hematologic Malignancies

By Rashmi Kumar, PhD, Senior Manager, Clinical Content; Courtney Smith, PhD, Oncology Scientist/Medical Writer; and Hema Sundar, PhD, Oncology Scientist/Senior Medical Writer

On Friday, September 19, and Saturday, September 20, 2014, the National Comprehensive Cancer Network® (NCCN®) hosted its 9th Annual Congress: Hematologic Malignancies™.

Moderated by Andrew D. Zelenetz, MD, PhD, Memorial Sloan Kettering Cancer Center and NCCN Guidelines Panel Chair for Non-Hodgkin’s Lymphomas (NHL), this year’s event focused on the new approaches to patient management and updates incorporated into the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for hematologic malignancies, as well as associated supportive care. More than 600 oncology professionals attended the event, which featured expert speakers from the NCCN Member Institutions.

Friday’s session commenced with opening remarks from Dr. Zelenetz, followed by two presentations on Chronic Myelogenous Leukemia (CML).

Neil P. Shah, MD, PhD, UCSF Helen Diller Family Comprehensive Cancer Center, outlined potential strategies to reduce high costs associated with tyrosine kinase inhibitor (TKI) therapy and optimize the management of CML. Switching to an alternate TKI, if early response is not achieved with imatinib, is one approach. The second approach, which is currently being investigated in clinical trials, is stopping TKI therapy in select patients with deep durable molecular remission, explained Dr. Shah. Jerald P. Radich, MD, Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance talked about the importance of molecular monitoring in CML. Molecular response at three months after starting TKI therapy is an established predictor of clinical outcome; however, if this response milestone is not achieved, there are no data supporting that change of therapy improves treatment outcome, Dr. Radich acknowledged. Mutational analyses, use of more sensitive molecular monitoring techniques, and evaluation of adherence to therapy may provide additional information, he added.

Joseph C. Alvarnas, MD, City of Hope Comprehensive Cancer Center, and Jae H. Park, MD, Memorial Sloan Kettering Cancer Center, concluded the first day with adjacent talks on the current management and developing therapeutics for acute lymphoblastic leukemia (ALL).  Dr. Alvarnas emphasized age as a significant confounding factor in treatment outcome; however, identification of ALL subtypes and implementation of minimal residual disease monitoring may improve future treatments. Dr. Park focused on chimeric antigen receptors (CAR) T-cell , presenting data from clinical trials using CARs as adaptive therapy for relapsed/refractory ALL. Data suggest that CARs are a promising treatment and are continuously evolving. “Armored CARs,” the fourth generation, are designed to reduce systemic toxicities.

The second day of the congress featured 13 presentations, including a debate between Sergio A. Giralt, MD, Memorial Sloan Kettering Cancer Center, and Kenneth C. Anderson, MD, Dana-Farber/Brigham and Women's Cancer Center, on the role of upfront autologous stem cell transplantation (SCT) in the current management of patients with symptomatic multiple myeloma. Dr. Giralt contended that the available data support the upfront use of SCT in all transplant-eligible patients, including those who achieve a complete response to primary therapy, as studies show higher rates of prolonged disease control associated with SCT. While not opposed to SCT, Dr. Anderson asserted that the extent of response seen after primary therapy with novel agents is unprecedented, and maintenance therapy further prolongs both progression-free and overall survival with or without SCT. Dr. Anderson said ongoing trials evaluating the role of upfront versus delayed SCT will provide clear answers to this debate in the near future. Until then, not all newly diagnosed patients need early transplantation therapy, he said.

Jennifer R. Brown, MD, PhD, Dana-Farber/Brigham and Women’s Cancer Center, and William G. Wierda, MD, PhD, The University of Texas MD Anderson Cancer Center, discussed the molecular prognostication and novel therapeutic options in chronic lymphocytic leukemia (CLL). Dr. Brown highlighted the potential clinical implications of mutations in NOTCH1, SF3B1, and BIRC3 genes. While these mutations portend an adverse prognosis, there is very little data about their role in therapy selection. Dr. Brown acknowledged that the presence of these mutations along with del(17p) identifies patients with high-risk CLL who need closer monitoring. Dr. Wierda presented data from clinical trials that led to the recent FDA approval of ibrutinib and idelalisib for relapsed/refractory CLL, emphasizing that clinicians should consider personalizing treatment options. 

Following the discussion of CLL, a cadre of supportive care interventions were examined. Laura Zitella, RN, MS, ACNP-BC, Stanford Cancer Institute, outlined the NCCN Guidelines® recommendations for the prevention of infections. The talk included the appropriate use of vaccinations and concluded by discussing most frequently addressed patient questions. Dr. Jeffrey Crawford, MD, Duke Cancer Institute, elaborated on the appropriate use of myeloid growth factors (MGF) to reduce the risk of febrile neutropenia. A review of data from randomized trials showed a reduction in mortality with MGF treatment; however, it was acknowledged that prospective studies assessing the cost/benefit of MGFs are necessary.

Jeremy S. Abramson, MD, Massachusetts General Hospital Cancer Center, began discussions of targeted therapy in the management of non-Hodgkin's lymphomas (NHL) with an overview of basic approaches to targeted therapy in indolent NHLs, focusing on therapies targeting the cell surface proteins, intracellular pathways (e.g., B-cell receptor signalling cascade), apoptotic pathways (e.g., PD-1 blockade), and tumor microenvironment.  With the increasing availability of novel targeted therapies, Dr. Abramson concurred that the therapeutic landscape for indolent NHLs is rapidly evolving, becoming less reliant on traditional cytotoxic therapy. Issa F. Khouri, MD, The University of Texas MD Anderson Cancer Center, continued the discussion, suggesting that incorporation of novel targeted therapies into maintenance therapy after transplant could improve outcomes in patients with mantle cell lymphomas. Leo I. Gordon, MD, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, commented on the use of targeted therapies to overcome the adverse impact of the non-germinal center diffuse large B-cell lymphoma (DLBCL) and individualizing therapy based on either cell of origin or mutation status.

In his presentation, Peter L. Greenberg, MD, Stanford Cancer Institute, described myelodysplastic syndromes (MDS) as a model for the evolution of a benign malignancy to an aggressive disease. He highlighted data that suggests a majority of MDS patients have at least one oncogenic mutation, though consistent mutations are not observed. Therefore, recent publications addressing the implication of these mutations in pathogenesis focus on determining critical, driver, and/or targetable mutations. In concert with classification by the Revised International Prognostic Scoring System (IPSS-r), the data presented suggest that molecular analyses may be used to advance classification and prognostication of MDS.

The final presentation of the congress was from Eunice S. Wang, MD, Roswell Park Cancer Institute, who reviewed changes in the current management of acute myeloid leukemia (AML). The talk focused on improving treatment for older patients, emphasizing that a numeric value for age is less important than the presence of factors associated with increasing age. Data from studies showing improved outcomes for older patients when treated on a higher intensity regimen were summarized. Dr. Wang concluded with identifying AML cytogenetic and molecular profiles that may benefit from the use of targeted therapies.

The congress concluded with closing remarks from Dr. Zelenetz.

For more information about the NCCN Annual Congress: Hematologic Malignancies, visit NCCN.org/HEM.

Look for further announcements in upcoming editions of NCCN eBulletin regarding continuing education opportunities based on presentations from the NCCN 9th Annual Congress: Hematologic Malignancies™.