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JAK2 R683S Mutation Resulting in Dual Diagnoses of Chronic Eosinophilic Leukemia and Myelodysplastic/Myeloproliferative Overlap Syndrome

Nathan M. Krah, Laura Miotke, Peng Li, Jay L. Patel, Anneli R. Bowen, Anthony D. Pomicter, and Ami B. Patel

A 66-year-old male presented with hypereosinophilia, thrombocytosis, extensive thrombosis refractory to direct oral anticoagulant therapy, and evidence of end-organ damage, including rash, splenic infarcts, and pulmonary infiltrates. Bone marrow biopsy revealed myeloid malignancy consistent with both chronic eosinophilic leukemia and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with SF3B1 mutation and thrombocytosis. Next-generation sequencing of the patient’s eosinophils and neutrophil compartments revealed pathologic variants in EZH2 and SF3B1 in addition to a noncanonical JAK2 R683S mutation that has not been previously described in myeloproliferative disorders or other chronic myeloid neoplasms. These mutations were not present in the patient’s lymphoid cell fraction, suggesting that the hematopoietic malignancy arose in a myeloid-committed progenitor cell. Based on this case and previous work from our group, we propose that noncanonical JAK2 mutations may permit signal transduction that biases toward eosinophilic differentiation in chronic myeloid neoplasms. Although the patient’s blood counts initially responded to ruxolitinib and hydroxyurea, the response was not durable. Early referral for allogenic bone marrow transplant appears necessary to prevent long-term complications and disease progression in myeloid neoplasms with clonal hypereosinophilia driven by noncanonical JAK2 mutations.

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Letter to Santa

Margaret Tempero

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Multiple Myeloma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology

Shaji K. Kumar, Natalie S. Callander, Kehinde Adekola, Larry D. Anderson Jr, Muhamed Baljevic, Rachid Baz, Erica Campagnaro, Jorge J. Castillo, Caitlin Costello, Christopher D’Angelo, Srinivas Devarakonda, Noura Elsedawy, Alfred Garfall, Kelly Godby, Jens Hillengass, Leona Holmberg, Myo Htut, Carol Ann Huff, Malin Hultcrantz, Yubin Kang, Sarah Larson, Hans C. Lee, Michaela Liedtke, Thomas Martin, James Omel, Timothy Robinson, Aaron Rosenberg, Douglas Sborov, Mark A. Schroeder, Daniel Sherbenou, Attaya Suvannasankha, Jason Valent, Asya Nina Varshavsky-Yanovsky, Rashmi Kumar, and Jenna Snedeker

The treatment of relapsed/refractory multiple myeloma (MM) has evolved to include several new options. These include new combinations with second generation proteasome inhibitors (PI); second generation immunomodulators, monoclonal antibodies, CAR T cells, bispecific antibodies, selinexor, venetoclax, and many others. Most patients with MM undergo several cycles of remissions and relapse, and therefore need multiple lines of combination therapies. Selecting treatment options for relapsed/refractory MM requires consideration of resistance status to specific classes, and patient-specific factors such as age and other comorbidities should be considered. The NCCN Guidelines for MM provide a framework on which to base decisions regarding workup, treatment, and follow-up of newly diagnosed and previously treated MM. This manuscript outlines the recommendations from NCCN Guidelines for MM specific to relapsed/refractory disease.

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NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024

Featured Updates to the NCCN Guidelines

Nadeem R. Abu-Rustum, Catheryn M. Yashar, Rebecca Arend, Emma Barber, Kristin Bradley, Rebecca Brooks, Susana M. Campos, Junzo Chino, Hye Sook Chon, Marta Ann Crispens, Shari Damast, Christine M. Fisher, Peter Frederick, David K. Gaffney, Stephanie Gaillard, Robert Giuntoli II, Scott Glaser, Jordan Holmes, Brooke E. Howitt, Jayanthi Lea, Gina Mantia-Smaldone, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Mirna Podoll, Kerry Rodabaugh, Ritu Salani, John Schorge, Jean Siedel, Rachel Sisodia, Pamela Soliman, Stefanie Ueda, Renata Urban, Emily Wyse, Nicole R. McMillian, Shaili Aggarwal, and Sara Espinosa

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

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NCCN News

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Patient Navigation for Timely, Guideline-Adherent Adjuvant Therapy for Head and Neck Cancer: A National Landscape Analysis

Evan M. Graboyes, Michelle Chappell, Kelsey A. Duckett, Katherine Sterba, Chanita Hughes Halbert, Elizabeth G. Hill, Bhishamjit Chera, Jessica McCay, Sidharth V. Puram, Salma Ramadan, Vlad C. Sandulache, Russel Kahmke, Brian Nussenbaum, Anthony J. Alberg, Electra D. Paskett, and Elizabeth Calhoun

Background: Aligned with the NCCN Clinical Practice Guidelines in Oncology for Head and Neck Cancers, in November 2021 the Commission on Cancer approved initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery for head and neck cancer (HNC) as its first and only HNC quality metric. Unfortunately, >50% of patients do not commence PORT within 6 weeks, and delays disproportionately burden racial and ethnic minority groups. Although patient navigation (PN) is a potential strategy to improve the delivery of timely, equitable, guideline-adherent PORT, the national landscape of PN for this aspect of care is unknown. Materials and Methods: From September through November 2022, we conducted a survey of health care organizations that participate in the American Cancer Society National Navigation Roundtable to understand the scope of PN for delivering timely, guideline-adherent PORT for patients with HNC. Results: Of the 94 institutions that completed the survey, 89.4% (n=84) reported that at least part of their practice was dedicated to navigating patients with HNC. Sixty-eight percent of the institutions who reported navigating patients with HNC along the continuum (56/83) reported helping them begin PORT. One-third of HNC navigators (32.5%; 27/83) reported tracking the metric for time-to-PORT at their facility. When estimating the timeframe in which the NCCN and Commission on Cancer guidelines recommend commencing PORT, 44.0% (37/84) of HNC navigators correctly stated ≤6 weeks; 71.4% (60/84) reported that they did not know the frequency of delays starting PORT among patients with HNC nationally, and 63.1% (53/84) did not know the frequency of delays at their institution. Conclusions: In this national landscape survey, we identified that PN is already widely used in clinical practice to help patients with HNC start timely, guideline-adherent PORT. To enhance and scale PN within this area and improve the quality and equity of HNC care delivery, organizations could focus on providing better education and support for their navigators as well as specialization in HNC.

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Physical Activity is Medicine

Alfredo Carrato

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Pilot Trial of Streamlined Genetic Education and Traceback Genetic Testing in Prostate Cancer Survivors

Marc D. Schwartz, Beth N. Peshkin, Claudine Isaacs, Christopher Grisham, Nora J. Holmes, Lia J. Sorgen, Sean Collins, Nancy Dawson, Colleen McGuire, Tobechukwu Okobi, Kelsey Newell, Kavitha A. Kolla, and Veronique Weinstein

Background: Germline genetic testing is recommended for men with metastatic or high-risk prostate cancer to inform treatment and risk management for other cancers and inform genetic testing in at-risk relatives. However, relatively few patients with prostate cancer undergo genetic testing. Given the low rate of testing and increasing demands on genetic service providers, strategies are needed that reduce barriers to testing while conserving genetic counseling resources. The primary goal of this study was to determine whether a proactive and streamlined “traceback” approach could yield increased genetic testing participation among prostate cancer survivors. Methods: We randomized 107 survivors of metastatic and high-risk prostate cancer to streamlined testing (ST) versus enhanced usual care (EUC). ST participants were proactively provided with print genetic education materials and the option to proceed to genetic testing without pre-test genetic counseling. EUC participants were sent a letter from their physician advising them of their eligibility for genetic testing and recommending they schedule genetic counseling. The primary outcome was genetic testing participation. Secondary outcomes were distress, knowledge, decision satisfaction, and regret. Results: In the ST group, 41.5% of participants completed genetic testing compared with 27.8% in the EUC group. After adjusting for education and marital status, the odds of testing were more than twice as high for the ST group as for the EUC group (odds ratio, 2.57; 95% CI, 1.05–6.29). The groups did not differ on any of the psychosocial outcomes at the 3-month follow-up. Conclusions: Proactive outreach paired with streamlined genetic testing delivery may be a safe, effective, and resource-efficient approach to facilitate traceback genetic testing in prostate cancer survivors.

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Similar Efficacy Observed for First-Line Immunotherapy in Racial/Ethnic Minority Patients With Metastatic NSCLC

Matthew Lee, Jianyou Liu, Emily Miao, Shuai Wang, Frank Zhang, John Wei, Julie Chung, Xiaonan Xue, Balazs Halmos, H. Dean Hosgood, and Haiying Cheng

Background: Limited data exist on the impact of immunotherapy use in ethnic minority patients with non–small cell lung cancer (NSCLC), because they have been underrepresented in immunotherapy trials. This study aims to evaluate race/ethnicity and other demographic, socioeconomic, and clinical factors of patients with metastatic NSCLC treated with first-line immunotherapy. Methods: A retrospective cohort study of 5,920 patients diagnosed with lung cancer treated at Montefiore Einstein Cancer Center from January 1, 2013, to June 1, 2022, was used to identify patients with metastatic NSCLC without EGFR, ALK, or ROS1 alterations who underwent first-line immunotherapy (n=248). The primary endpoint was overall survival (OS), with secondary endpoints of progression-free survival (PFS) and time to discontinuation (TTD) from the start of immunotherapy. Results: Among the 248 patients, median follow-up time was 12.0 months, median age at start of treatment was 66 years, and 39.1% were non-Hispanic Black, 30.2% were Hispanic, and 30.7% were non-Hispanic White. OS (P=.39), PFS (P=.29), and TTD (P=.98) were similar among racial/ethnic groups. Patients with an ECOG performance status (PS) of <2 at the start of immunotherapy had longer OS compared with those with ECOG PS of ≥2 (P<.0001). PD-L1 expression (<50% vs ≥50%; P=.03) and body mass index (BMI) (P=.01) were also found to be associated with PFS, and ECOG PS (P<.0001) and BMI (P=.02) were associated with TTD. In a multivariate analysis of OS and PFS, ECOG PS was the only variable found to be significant. Conclusions: Our study observed similar benefits of immunotherapy in patients with metastatic NSCLC in different racial and ethnic groups. Furthermore, ECOG PS was associated with OS, and PD-L1 expression and BMI were associated with PFS and TTD. These findings help identify potential factors associated with outcomes and care while patients are undergoing immunotherapy.

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What Constitutes Quality of Life? Perspectives of Adolescents and Young Adults With Advanced Cancer

Jane Hinkle, Lori Wiener, Andrea Altschuler, Katharine E. Brock, Mallory Casperson, Chun R. Chao, Lauren Fisher, Lawrence H. Kushi, Joshua R. Lakin, Anna Lefebvre, Corey M. Schwartz, Dov M. Shalman, Catherine B. Wall, and Jennifer W. Mack

Background: Adolescents and young adults (AYAs) with advanced cancer identify maintaining a good quality of life (QoL) as a central goal of end-of-life care. QoL is a dynamic and subjective overarching concept that refers to an individual’s relative satisfaction with their own life. Despite its importance to AYAs with advanced cancer, a patient-centered definition of QoL is lacking in this population. Patients and Methods: This qualitative secondary analysis of semistructured interviews was conducted across 3 institutions and 1 online support community among AYA patients with advanced cancer, family caregivers, and health care providers who cared for living or recently deceased AYAs. Interviewees were asked about priorities in receipt of care. Interviews were transcribed using NVivo software for primary analysis, and previously coded excerpts were screened for references to QoL. Relevant excerpts were sorted into organizing domains. Results: Participants included 23 AYA patients, 28 family caregivers, and 29 health care providers (including physicians, nurses, nurse practitioners, social workers, and psychologists). Four domains of QoL were identified: psychosocial and physical well-being, dignity, normalcy, and personal and family relationships. Within each domain there was agreement across AYAs, caregivers, and health care providers, with nuanced perspectives provided by AYAs of different ages. Personal and family relationships was the most frequently referenced domain of QoL among all participants. A common feature of each domain was that adaptation to current circumstances impacted perspectives on QoL. Patients valued active participation in the development of a care plan that supported these domains. Conclusions: AYAs with advanced cancer, their caregivers, and health care providers agree on several broad domains of QoL in this population. To provide high-quality, patient-centered care, care plans should integrate these domains to enable AYAs to maximize their QoL throughout their advanced cancer care.