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Anil K. Rengan and Crystal S. Denlinger

Abstract

Futibatinib is a novel FGFR inhibitor currently under investigation as a second-line treatment for locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene fusions and rearrangements. As FGFR-targeted therapies move into the frontline setting, sequencing of these drugs remains undetermined. To date, no study has investigated the use of futibatinib in the context of pemigatinib resistance. We describe a 50-year-old woman with metastatic FGFR-aberrant intrahepatic cholangiocarcinoma who showed a robust response to futibatinib for 23.6 months, having previously benefited from pemigatinib. Futibatinib was safely used despite her history of decompensated cirrhosis and significant cytopenias. We observed a reduction in CA 19-9 level and a partial radiographic response on futibatinib. Serial next-generation sequencing and cell-free DNA testing proved crucial to making appropriate treatment decisions.

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Emily A. Harlan and Andrew G. Shuman

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Andrew J. Portuguese, Scott S. Tykodi, Christopher D. Blosser, Ted A. Gooley, John A. Thompson, and Evan T. Hall

Chronic immunosuppression in solid organ transplant recipients (SOTRs) leads to an increased risk of a wide variety of cancers. Immune checkpoint inhibitor (ICI) therapy is indicated for many of these; however, the risks and benefits of ICI use in the SOTR population have not been well characterized. We performed a systematic literature review identifying 119 reported cases of ICI use among SOTRs. Treatments used included PD-1 inhibition (75.6%), CTLA-4 inhibition (12.6%), PD-L1 inhibition (1.7%), and combination and/or sequential ICI therapy (10.1%). The most common cancers included cutaneous melanoma (35.3%), hepatocellular carcinoma (22.7%), and cutaneous squamous cell carcinoma (18.5%). The overall objective response rate (ORR) was 34.5%, with a median duration of response of 8.0 months. Ongoing response was seen in 21.0%. Cutaneous squamous cell carcinoma had significantly better ORR compared with other cancer types (68.2% vs 26.8%; odds ratio [OR], 5.85; P =.0006). Factors associated with improved ORR included increasing time from transplant to ICI (OR, 1.09; P =.008) and preemptive reduction in intensity of the graft maintenance immunosuppressive regimen (50.0% vs 18.5%; OR, 4.40; P =.0088). Rejection occurred in 41.2%, graft failure in 23.5%, and immune-related adverse events in 18.5%. Factors significantly associated with allograft rejection included allograft PD-L1 positivity (100% vs 0%; P<.0001) and absence of tacrolimus in the immunosuppressive regimen (48.7% vs 25.6%; OR, 0.36; P =.019). The most common cause of death was progressive malignancy (64.0%), followed by graft failure (24.0%). Our analysis provides current benchmark data to help inform management of SOTRs with advanced cancers that are reflected by our patient cohort. Biomarker development, more robust datasets, and prospective study of concomitant immunosuppression management may help refine decision-making in this complex scenario in the future. Close coordination of care between the medical oncologist and transplant specialist is encouraged to help optimize treatment outcomes.

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Andrew Hantel, Michael L. McManus, Martha Wadleigh, Michael Cotugno, and Gregory A. Abel

Background: Intermittent shortages of chemotherapeutics used to treat curable malignancies are a worldwide problem that increases patient mortality. Although multiple strategies have been proposed for managing these shortages (eg, prioritizing patients by age, scarce treatment efficacy per volume, alternative treatment efficacy difference), critical clinical dilemmas arise when selecting a management strategy and understanding its impact. Patients and Methods: We developed a model to compare the impact of different allocation strategies on overall survival during intermittent chemotherapy shortages and tested it using vincristine, which was recently scarce for 9 months in the United States. Demographic and treatment data were abstracted from 1,689 previously treated patients in our tertiary-care system; alternatives were abstracted from NCCN Clinical Practice Guidelines in Oncology for each disease and survival probabilities from the studies cited therein. Modeled survival was validated using SEER data. Nine-month shortages were modeled for all possible supply levels. Pairwise differences in 3-year survival and risk reductions were calculated for each strategy compared with standard practice (first-come, first-served) for each 50-mg supply increment, as were supply thresholds above which each strategy maintained survival similar to scenarios without shortages. Results: A strategy prioritizing by higher vincristine efficacy per volume and greater alternative treatment efficacy difference performed best, improving survival significantly (P<.01) across 86.5% of possible shortages (relative risk reduction, 8.3%; 99% CI, 8.0–8.5) compared with standard practice. This strategy also maintained survival rates similar to a model without shortages until supply fell below 72.2% of the amount required to treat all patients, compared with 94.3% for standard practice. Conclusions: During modeled vincristine shortages, prioritizing patients by higher efficacy per volume and alternative treatment efficacy difference significantly improved survival over standard practice. This approach can help optimize allocation as intermittent chemotherapy shortages continue to arise.

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Margaret Tempero

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John A. Thompson, Bryan J. Schneider, Julie Brahmer, Amaka Achufusi, Philippe Armand, Meghan K. Berkenstock, Shailender Bhatia, Lihua E. Budde, Saurin Chokshi, Marianne Davies, Amro Elshoury, Yaron Gesthalter, Aparna Hegde, Michael Jain, Benjamin H. Kaffenberger, Melissa G. Lechner, Tianhong Li, Alissa Marr, Suzanne McGettigan, Jordan McPherson, Theresa Medina, Nisha A. Mohindra, Anthony J. Olszanski, Olalekan Oluwole, Sandip P. Patel, Pradnya Patil, Sunil Reddy, Mabel Ryder, Bianca Santomasso, Scott Shofer, Jeffrey A. Sosman, Yinghong Wang, Vlad G. Zaha, Megan Lyons, Mary Dwyer, and Lisa Hang

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions, consisting of medical and hematologic oncologists with expertise across a wide range of disease sites, and experts from the areas of dermatology, gastroenterology, endocrinology, neurooncology, nephrology, cardio-oncology, ophthalmology, pulmonary medicine, and oncology nursing. The content featured in this issue is an excerpt of the recommendations for managing toxicities related to CAR T-cell therapies and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to immune checkpoint inhibitors, visit NCCN.org.

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NCCN Guidelines® Insights: Hodgkin Lymphoma, Version 2.2022

Featured Updates to the NCCN Guidelines

Richard T. Hoppe, Ranjana H. Advani, Weiyun Z. Ai, Richard F. Ambinder, Philippe Armand, Celeste M. Bello, Cecil M. Benitez, Weina Chen, Bouthaina Dabaja, Megan E. Daly, Leo I. Gordon, Neil Hansen, Alex F. Herrera, Ephraim P. Hochberg, Patrick B. Johnston, Mark S. Kaminski, Christopher R. Kelsey, Vaishalee P. Kenkre, Nadia Khan, Ryan C. Lynch, Kami Maddocks, Jonathan McConathy, Monika Metzger, David Morgan, Carolyn Mulroney, Sheeja T. Pullarkat, Rachel Rabinovitch, Karen C. Rosenspire, Stuart Seropian, Randa Tao, Pallawi Torka, Jane N. Winter, Joachim Yahalom, Joanna C. Yang, Jennifer L. Burns, Mallory Campbell, and Hema Sundar

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte–predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.