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Words Matter: Unintended Side Effects of “Financial Toxicity”

Eric C. Blackstone and Barbara J. Daly

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Volume 21 (2023): Issue Supplement (Nov 2023): Highlights of the NCCN 2023 Annual Congress: Hematologic Malignancies

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Acute Myeloid Leukemia: Selecting Induction Therapy Based on Biological Disease Factors

Presented by: Rebecca Olin

Greater insight into the role of biologic disease factors in acute myeloid leukemia (AML) has led to more effective and personalized treatment options. Data presented at the NCCN 2023 Annual Congress: Hematologic Malignancies reflected the rapidly evolving treatment landscape, showcasing the significance of combination therapies and precision medicine in managing different AML subtypes. For patients deemed fit for induction with favorable-risk cytogenetics, the standard of care has moved to combining the 7 + 3 regimen with gemtuzumab ozogamicin. Alternatively, for patients with FLT3-mutated disease, a more intensified approach involving the addition of midostaurin or newer therapies, such as quizartinib, to standard induction treatment has shown improved outcomes. For patients with AML who are unfit for standard induction, treatments combining hypomethylating agents with venetoclax, as well as therapies involving IDH1/2 and FLT3 inhibitors for specific genetic subtypes, offer encouraging alternatives in managing the disease.

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Adult Acute Lymphocytic Leukemia: Strategies for Selection of Consolidation Therapy

Presented by: Aaron C. Logan

The 2 primary treatment options for adult acute lymphoblastic leukemia (ALL) are pediatric-inspired Berlin-Frankfurt-Münster protocols and the hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen—these treatment strategies are now being augmented with novel agents. Current strategies also emphasize measurable residual disease (MRD) quantification as a critical tool for determining the treatment course. For patients with MRD-positive ALL, the standard of care has shifted toward blinatumomab, resulting in improved outcomes and survival rates. Another novel agent, inotuzumab ozogamicin, is also being explored for the treatment of earlier stages of disease in patients with ALL. For Philadelphia chromosome (Ph)–negative ALL, the NCCN Guidelines recommend treatment with blinatumomab followed by allogeneic transplants for patients remaining MRD-positive after initial therapy. For patients achieving MRD negativity at the level of 10-4, blinatumomab is now recommended as consolidation, with or without subsequent allotransplant, depending on patient disease risk features. For Ph-positive ALL, the use of tyrosine kinase inhibitors in combination with blinatumomab has demonstrated excellent efficacy, indicating the growing importance of combination targeted therapies to improve outcomes and decrease the toxicity of therapy in adults with ALL.

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Advances in the Management of Classical Hodgkin Lymphoma

Presented by: Ryan C. Lynch

The development of brentuximab vedotin, nivolumab, and pembrolizumab has revolutionized the treatment of classical Hodgkin lymphoma. Continuous efforts are underway to improve the established early-line treatment regimens, incorporating these novel systemic therapies as either replacements for or additions to conventional agents. Although brentuximab vedotin, nivolumab, and pembrolizumab have demonstrated efficacy both as monotherapies and in combinations, critical questions remain regarding the sequencing of these agents, as well as the role of radiation therapy and interim PET scans.

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Chronic Myeloid Leukemia/Myelofibrosis: TKI Therapy and Toxicity Management

Presented by: Gabriela S. Hobbs and Christopher Bell

Recent advances in the understanding of the molecular basis of chronic myeloid leukemia (CML) and myelofibrosis have led to more effective treatment options, with survival now close to that of age-matched controls in CML. The latest updates to the NCCN Guidelines for CML reflect the rapidly evolving treatment landscape, emphasizing the increasing importance of personalized medicine and various targeted therapies. For patients with CML, standard of care involves tyrosine kinase inhibitors such as imatinib, dasatinib, bosutinib, nilotinib, ponatinib, and asciminib, tailored to patient-specific factors and the severity of adverse events. In patients with myelofibrosis, the Janus kinase inhibitors ruxolitinib, pacritinib, and fedratinib have yielded improved outcomes. Critical strategies for managing treatment-related adverse events to optimize the quality of life for patients with these hematologic malignancies were also highlighted.

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Incorporating Immunotherapeutic Strategies in the Management of Relapsed/Refractory Multiple Myeloma

Presented by: Shaji K. Kumar

The emergence of immunotherapy has changed the treatment strategy for multiple myeloma, both in the early disease setting and in relapsed/refractory disease. Although daratumumab has been routinely incorporated into various combination regimens, T-cell–redirecting approaches, such as bispecific T-cell engagers and CAR T-cell therapy, are emerging. In patients with highly refractory disease, these approaches have robustly impacted both progression-free and overall survival. Most of these agents target the B-cell maturation antigen. Drugs with new targets are also in development, which will further extend the value of immunotherapeutic strategies in myeloma.

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Management of Newly Diagnosed Multiple Myeloma Based on Risk Stratification

Presented by: Natalie S. Callander

In the context of newly diagnosed multiple myeloma, recent advances in risk assessment have influenced treatment decisions and paved the way for more individualized approaches. The current NCCN Guidelines for Multiple Myeloma outline the updated staging system, highlight various high-risk features for disease progression/relapse, and provide evidence-based recommendations for myeloma therapy. Although the therapeutic landscape continues to shift toward increased risk adaptability, ongoing efforts should place an emphasis on tackling modifiable risks.

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Management of Toxicities of BTK Inhibitors in B-Cell Malignancies

Presented by: Muhammad Saad Hamid and Kirollos S. Hanna

Brüton’s tyrosine kinase (BTK) inhibitors have significantly advanced treatment options for patients with B-cell malignancies; however, side effects with these agents are not uncommon, and a multidisciplinary approach is necessary for monitoring and managing adverse events such as bleeding, hypertension, and atrial fibrillation. In the treatment of patients on BTK inhibitors, maintaining communication between patients and all providers is essential, particularly concerning the use of any concurrent medications or supplements, as is educating patients on identifying early risk factors and reporting any signs or symptoms of toxicities. Ongoing clinical studies with both covalent and noncovalent BTK inhibitors are expected to further increase the understanding of these toxicities while improving the efficacy and safety of this class of medications.

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Navigating the Challenges: Effective Management of Toxicities in CAR T-Cell Therapies

Presented by: Olalekan O. Oluwole and Salyka Sengsayadeth

CAR T-cell therapy has dramatically changed the treatment landscape of many hematologic cancers, but it carries some risk. Cytokine-release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome can be life-threatening acute toxicities that require prompt identification, severity grading, and intervention. Appropriate use of tocilizumab and steroids may mitigate the side effects of CRS. Some of the chronic toxicities, such as cytopenias and hypogammaglobulinemia, should be differentiated from other possible causes; they also may respond to well-informed management.