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NCCN Annual Congress Explores Latest Advances in Treating Hematologic Malignancies

By Rashmi Kumar, PhD, Director, Clinical Information Operations; Ndiya Ogba, PhD, Oncology Scientist/Medical Writer; & Hema Sundar, PhD, Oncology Scientist/Senior Medical Writer

On Friday, October 6, and Saturday, October 7, 2017, the National Comprehensive Cancer Network® (NCCN®) hosted its 12th Annual Congress: Hematologic Malignancies™ in San Francisco, California.

The congress was moderated by Ranjana H. Advani, MD, Stanford Cancer Institute, Vice-Chair of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Panel for Hodgkin Lymphoma and member of the NCCN Guidelines® Panel for B-cell Lymphomas; and Andrew D. Zelenetz, MD, PhD, Memorial Sloan Kettering Cancer Center, Chair of the NCCN Guidelines Panel for B-cell Lymphomas.

The didactic presentations and patient case studies focused on the current standard of care and recent advances in the management of hematologic malignancies, including follicular lymphoma (FL), Hodgkin lymphoma (HL), multiple myeloma (MM), myeloproliferative neoplasms (MPN), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). 

Opening remarks by Dr. Advani on Friday were followed by three didactic presentations. Dr. Zelenetz reviewed the updates to the 2016 WHO classification of lymphoid neoplasms, focusing on the key changes to the classification of aggressive B-cell lymphomas. Determination of the cell of origin (germinal center B-cell vs activated B-cell) either by immunohistochemistry (IHC) or gene expression profiling is now required for the diagnosis of subtypes of diffuse large B-cell lymphoma (DLBCL), Dr. Zelenetz explained. Double-hit or triple-hit B-cell lymphomas have been reclassified as high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. Therefore, it is now important to evaluate BCL2 and MYC protein expression by IHC and perform molecular analysis to detect MYC, BCL2 or BCL6 gene rearrangements. These changes provide greater precision for the diagnosis, allowing for the development of more appropriately targeted therapies; however, this could also mean that certain groups of patients may be excluded from clinical trials evaluating specific targeted therapies, Dr. Zelenetz concluded.

Jane N. Winter, MD, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, discussed the updates to the treatment of FL. She provided an overview of current treatment options and reviewed data from clinical trials evaluating novel agents for the treatment of relapsed/refractory FL— PI3K inhibitors (duvelisib and copanlisib), checkpoint inhibitors (pembrolizumab), BCL-2 inhibitors (venetoclax), and antibody-drug conjugates (polatuzumab vedotin). Although overall survival has improved considerably for the vast majority of patients with FL, survival remains poor for the sub-group of patients who progress within 24 months of initial treatment. Dr. Winter highlighted the need to identify these high-risk patients and implement novel treatment strategies to improve their outcomes.

Dr. Advani provided an overview of standard and emerging options for the treatment of HL. Noting that the management of localized HL is a success story with high-cure rates, she stressed that there is a need for therapeutic options in advanced disease settings. Using a case study, Dr. Advani gave an overview of standard treatment options for patients with relapsed or refractory classical HL (CHL), including a list of chemotherapy regimens followed by autologous stem cell transplant (ASCT), and immunomodulatory agent, brentuximab vedotin. Recent results from the Echelon 1 trial suggest a role for brentuximab vedotin in front-line therapy for patients with advanced-stage CHL, when combined with standard ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) regimen. Dr. Advani also reviewed data for checkpoint inhibitors, nivolumab and pembrolizumab. Ongoing clinical trials are examining the prognostic impact of metabolic tumor volume, and the utility of lenalidomide, ibrutinib, ruxolitinib, panobinostat or chimeric antigen receptor (CAR) T-cell therapy as options for relapsed or refractory HL. Since new technologies are improving the understanding of the genetics of CHL, Dr. Advani concluded that some of the future challenges with these novel and emerging therapeutic options include access to resources and optimal use of treatments that target genetic abnormalities.

The session on Friday concluded with the first series of patient case studies and panel discussion presented by Mark W. Clemens II, MD, The University of Texas MD Anderson Cancer Center; Youn H. Kim, MD, Stanford Cancer Institute; and Dr. Zelenetz. The panelists discussed the diagnosis, workup, and treatment of splenic marginal zone lymphoma and two rare subtypes of T-cell lymphomas (breast implant-associated anaplastic large cell lymphoma and cutaneous T-cell lymphoma [Sezary syndrome]). 

On Saturday morning, sessions commenced with a presentation on the management of lymphoma survivors. Sharyn L. Kurtz, PA-C, MPAS, MA, Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center, provided a detailed overview of the various types of long-term/late effects of curative treatment involving multiple organ types. She also provided recommendations for periodic screening to identify and manage treatment-related toxicities in survivors of HL and non-Hodgkin’s lymphomas. She stressed the importance of providing a treatment summary and care plan at the completion of treatment, communicating with the community physician, developing evidence-based survivorship practices, and underscored the growing role for advance practice providers in the management of lymphoma survivors.

This was followed by patient case studies and interactive panel discussions on plasma cell neoplasms in which the panelists Shaji K. Kumar, MD, Mayo Clinic Cancer Center; Sandy W. Wong, MD, UCSF Helen Diller Family Comprehensive Cancer Center; and Natalie S. Callandar, MD, University of Wisconsin Carbone Cancer Center; focused on the key aspects of diagnosis, management, and special considerations for solitary plasmacytoma, systemic light chain amyloidosis, and MM in the elderly patients.

The case studies were followed by three presentations encompassing the overall management of patients with MM. Dr. Kumar presented the strategies for treating transplant eligible newly diagnosed patients with MM. He outlined important steps in the management of MM—accurate diagnosis, risk stratification of the individual patient, and durable disease control. The current standard of care for newly diagnosed patients is a triple-drug regimen with an immunomodulator (IMiD) and a proteosome inhibitor (PI). Data from the phase III SWOG S077 trial demonstrated that the triple-drug regimen bortezomib/lenalidomide/dexa­methasone (VRD) as initial therapy improved progression-free survival and overall survival (OS) compared with the doublet (lenalidomide/dexamethasone). Newer combinations of IMiDs and PIs are being explored to get better response and increase tolerability. Based on the promising data from phase II trials of carfilzomib/lenalidomide/dexamethasone (CRD) as initial therapy, there is an on-going phase III trial (E1A11) currently recruiting patients to compare VRD versus CRD as initial therapy. Similarly, another phase III trial (TOURMALINE MM-2) is evaluating the efficacy of ixazomib/lenalidomide/dexamethasone compared with lenalidomide/dexamethasone. Dr. Kumar also pointed out that ASCT continues to play an important role in consolidating, deepening, and maintaining response to initial treatment. The results of the IFM 2009 study clearly show the benefit of transplant in all groups of patients with the response being durable in those with no minimal residual disease (MRD) after initial therapy. Maintenance therapy further helps optimize responses achieved by primary therapy and ASCT. A recent meta-analysis of 3 randomized clinical trials found that lenalidomide maintenance after ASCT significantly improved OS compared with the controls. Dr. Kumar concluded his presentation by stressing the importance of administering supportive care in patients with MM.

“Despite major and continuing treatment interventions, MM remains incurable for most patients” shared Dr. Callandar, who discussed the appropriate evaluation for relapsed/refractory MM and the management strategies. She pointed out the rapid additions of new drugs and combinations to the treatment armamentarium over the past two years or so, which have contributed to dramatic improvement in survival rates of patients with MM. To help select appropriate treatment from the large list of options available, she mentioned that the NCCN panel has classified the regimens into the following categories: preferred regimens; other recommended regimens; and regimens useful under certain circumstances. Dr. Callandar illustrated with case studies how to tailor treatment approaches based on biology, frailty, comorbidities, lines of treatment, etc. She emphasized that clinical trials should always be considered, as there are many underway evaluating new drugs with new mechanism of action and the treatment paradigm continues to evolve.

The session on MM concluded with a talk by Kathleen Colson, RN, BSN, BS, Dana-Farber Cancer Institute, focusing on the management of common complications related to MM and its treatment. In her presentation, she described supportive care measures for the common clinical manifestations from MM such as bone-related issues, renal dysfunction, anemia, and infections. She highlighted the adverse effects associated with the newest agents such as daratumumab and elotuzumab in order to help anticipate and effectively manage them, thereby improve patient outcomes.

Thomas LeBlanc, MD, MA, Duke Cancer Institute, discussed palliative and end-of-life care in hematological malignancies, and the main objective of his presentation was to dispel inaccurate perceptions of palliative care. He started his talk by defining palliative care as “a specialized medical care for people facing a serious illness” with the focus on providing patients with symptom and stress relief and a goal of improving quality of life for the patient and caregiver. Despite accumulating evidence demonstrating the benefits of adding palliative care, he noted that more work is needed to better understand the unique needs of patients with hematologic malignancies and health care teams need to partner together to address them.

The afternoon session commenced with the patient case studies and panel discussion in which the panelists Ruben A. Mesa, MD, UT Health San Antonio Cancer Center; Neil P. Shah, MD, PhD, UCSF Helen Diller Family Comprehensive Cancer Center; William G. Wierda, MD, PhD, The University of Texas MD Anderson Cancer Center; discussed the management of disease progression of MPN to AML, criteria for the discontinuation of tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) in carefully selected patients, and the role of maintenance therapy in CLL.

Dr. Mesa presented the recommendations included in the recently published NCCN Guidelines for MPN for the diagnosis, risk stratification, and treatment of polycythemia vera (PV) and essential thrombocythemia (ET). The primary goal of therapy is to control disease-related symptoms and decrease the risk of vascular events, he noted. Therefore, quantification of symptoms through a patient-reported assessment tool should be an essential part of the management of patients with PV and ET, he emphasized. Dr. Mesa concluded his talk with a brief mention of the novel treatment options that are being evaluated in clinical trials.

Dr. Wierda reviewed the clinical data supporting the current treatment options for CLL and outlined potential strategies for the sequencing of therapy for relapsed/refractory disease. Del (17p) or TP53 mutation is more common in relapsed/refractory disease and CLL with del (17p) or TP53 mutation is not very responsive to chemoimmunotherapy. Therefore, it is essential to evaluate the mutation status before initiating treatment for relapsed/refractory disease, emphasized Dr. Wierda. In addition, it is also important to consider prior treatment (chemoimmunotherapy vs. ibrutinib), duration of remission, and refractoriness of the disease prior to treatment, Dr. Wierda explained. Long-term durable disease control is the goal of treatment for relapsed/refractory disease, and appropriate sequencing of therapy could prolong survival in this patient population, he concluded. 

David G. Maloney, MD, PhD, Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, presented on the new agents being used or considered for the management of ALL, particularly for disease that has relapsed or is refractory to treatment. Dr. Maloney began by emphasizing that adult patients with ALL experience poorer survival rates and there is a need for therapeutic agents that effectively combat relapsed or refractory disease. Data was presented for immunotherapies including rituximab, inotuzumab ozogamicin, blinatumomab and CAR T-cells, given the recent approvals of the last three agents as options for relapsed or refractory disease. Combining rituximab and inotuzumab ozogamicin with standard chemotherapy has demonstrated decreased relapse rates and improved survival rates. Dr. Maloney stressed the need for close monitoring of toxicity profiles and speculated on possible causes of neurotoxicity associated with immunotherapies. Ongoing clinical trials with CAR T-cell therapy are seeking to improve CAR T-cell persistence and thereby improve disease remission rates. For these new therapies, Dr. Maloney noted that a challenge would be determining how to sequence treatment, with the overarching goal of decreasing the need for allogeneic transplant.

Bruno Medeiros, MD, Stanford Cancer Institute, gave an overview of the new and emerging agents used as targeted therapy in the management of AML. “For the first time in two decades, we have new options for AML,” Dr. Medeiros stated, which ideally should decrease relapse rates in patients achieving a remission, improve response rates in patients with chemoresistant phenotypes, and decrease toxicities associated with current therapeutic strategies. He presented clinical data for several targeted therapies including FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase (IDH) inhibitors (midostaurin, crenolanib, gilterinib, quizartinib, enasidenib, or ivosidenib), hypomethylating agents (guadecitabine or oral azacitidine), immunotherapies (gemtuzumab ozogamicin, bispecific T-cell engager [BiTE]/dual-affinity re-targeting [DART] molecules, vadastuximab talirine) and new delivery methods for cytarabine and daunorubicin (CPX-351) used for upfront therapy and relapsed disease. For example, the addition of FLT3 inhibitor, midostaurin, to conventional therapy increased complete remission rates in patients with AML younger than 60 years of age. A few clinical trials are in progress using CAR T-cell therapy, although Dr. Medeiors noted that dual-targeting strategies might enhance the specificity and decrease off-target effects observed with this approach. Dr. Medeiros concluded that the current challenge would be determining effective use and sequencing of these new agents. Additionally, with several new promising agents in late-stage development, these agents have an immense potential to impact AML management.

An engaging 2-part talk on controversies that surround minimal residual disease (MRD) monitoring in AML was delivered as the last presentations. Jessica K. Altman, MD, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, and member of the NCCN Guidelines Panel for AML, set the stage by defining the concept of MRD and outlining steps that would lead a clinician to consider MRD assessment as a means of monitoring patient response to therapy. Dr. Altman postulated that ideally, MRD should provide prognostic information to the presenting features and guide risk stratification during disease management. She then gave a review of the current methods used to assess MRD, including flow cytometry and polymerase chain reaction (PCR)-based assays; however, a lack of defined markers and lack of standardized methods and disease thresholds represent challenges to their effective use in MRD monitoring. In addition, some data suggests patients without detectable MRD may still relapse. Dr. Altman noted that emerging technologies with increased sensitivities, including next-generation sequencing-based assays and digital PCR, might address this. Richard M. Stone, MD, Dana-Farber Cancer Institute, Vice-Chair of the NCCN Guidelines Panel for Myelodysplastic Syndromes (MDS) and member of the NCCN Guidelines Panel for AML, highlighted that in addition to the lack of standardization, high costs and the ambiguity of the potential impact on prognosis and clinical decision making also present major barriers to effective use of MRD assessment in the management of AML. Dr. Stone presented clinical data to support two potential ways to enhance the utility of MRD in AML—one, the development of therapeutic agents that eradicate measurable residual disease, and two, determining the efficacy of double umbilical cord transplant at diminishing poor prognosis based on MRD risk stratification. Both Dr. Altman and Dr. Stone concluded that overall, MRD assessment is important to include in clinical studies and there is a need for standardized guidelines to inform therapeutic decisions.

The congress concluded with closing remarks from Dr. Zelenetz and Dr. Advani.

Accredited materials from the congress will be available shortly through the NCCN Continuing Education Portal at education.nccn.org.

The NCCN 13th Annual Congress: Hematologic Malignancies is scheduled for Friday, September 21, and Saturday, September 22, 2018 in New York, New York.