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Abstract: The treatment of patients with relapsed and refractory Hodgkin lymphoma (HL), especially those who relapse after autologous stem cell transplantation, remains challenging. Patients with HL whose disease relapses after stem cell transplantation are rarely cured with current treatment modalities, and have a median survival of less than 3years. Since no new drugs have been approved by the FDA for HL in more than three decades, there is a clear unmet medical need for drug development for this patient population. New treatment strategies that are based on targeting oncogenic signaling pathways are currently explored. This review will focus on emerging new treatment modalities that are currently under investigation for patients with relapsed classical HL. [Copyright &y& Elsevier]

Purpose: To improve curability and limit long-term adverse effects for newly diagnosed early-stage (ES), unfavorable-risk Hodgkin lymphoma., Methods: In this multicenter study with four sequential cohorts, patients received four cycles of brentuximab vedotin (BV) and doxorubicin, vinblastine, and dacarbazine (AVD). If positron emission tomography (PET)-4-negative, patients received 30-Gy involved-site radiotherapy in cohort 1, 20-Gy involved-site radiotherapy in cohort 2, 30-Gy consolidation-volume radiotherapy in cohort 3, and no radiotherapy in cohort 4. Eligible patients had ES, unfavorable-risk disease. Bulk disease defined by Memorial Sloan Kettering criteria (> 7 cm in maximal transverse or coronal diameter on computed tomography) was not required for cohorts 1 and 2 but was for cohorts 3 and 4. The primary end point was to evaluate safety for cohort 1 and to evaluate complete response rate by PET for cohorts 2-4., Results: Of the 117 patients enrolled, 116 completed chemotherapy, with the median age of 32 years: 50% men, 98% stage II, 86% Memorial Sloan Kettering-defined disease bulk, 27% traditional bulk (> 10 cm), 52% elevated erythrocyte sedimentation rate, 21% extranodal involvement, and 56% > 2 involved lymph node sites. The complete response rate in cohorts 1-4 was 93%, 100%, 93%, and 97%, respectively. With median follow-up of 3.8 years (5.9, 4.5, 2.5, and 2.2 years for cohorts 1-4), the overall 2-year progression-free and overall survival were 94% and 99%, respectively. In cohorts 1-4, the 2-year progression-free survival was 93%, 97%, 90%, and 97%, respectively. Adverse events included neutropenia (44%), febrile neutropenia (8%), and peripheral neuropathy (54%), which was largely reversible., Conclusion: BV + AVD × four cycles is a highly active and well-tolerated treatment program for ES, unfavorable-risk Hodgkin lymphoma, including bulky disease. The efficacy of BV + AVD supports the safe reduction or elimination of consolidative radiation among PET-4-negative patients., Competing Interests: Anita KumarStock and Other Ownership Interests: BridgebioConsulting or Advisory Role: Celgene, Kite, a Gilead company, AstraZenecaResearch Funding: AbbVie/Genentech, Adaptive Biotechnologies, Celgene, Seattle Genetics, AstraZeneca, Pharmacyclics Carla CasuloHonoraria: Gilead SciencesResearch Funding: Celgene, Verastem, Gilead SciencesTravel, Accommodations, Expenses: Gilead Sciences, Roche Ranjana H. AdvaniConsulting or Advisory Role: Genentech/Roche, Seattle Genetics, Takeda, Portola Pharmaceuticals, Celgene, Sanofi, Kura Oncology, Merck, Karyopharm Therapeutics, ADC Therapeutics, Daiichi Sankyo, Bristol Myers Squibb/Celgene, Epizyme, IncyteResearch Funding: Millennium, Seattle Genetics, Genentech/Roche, Pharmacyclics, Janssen, Merck, Kura Oncology, Regeneron, Forty Seven, Cyteir Elizabeth BuddeHonoraria: AstraZenecaConsulting or Advisory Role: Roche/Genentech, Kite/Gilead, NovartisSpeakers' Bureau: Kite, a Gilead company, AstraZenecaResearch Funding: Merck, Amgen, MustangBio, AstraZenecaPatents, Royalties, Other Intellectual Property: CCR4 CAR T cells for treatment of patients with CCR4 positive cancer, CD33CAR for treatment of patients with CD33+ acute myeloid leukemiaTravel, Accommodations, Expenses: Roche/Genentech, Kite/Gilead, AstraZeneca Paul M. BarrConsulting or Advisory Role: Pharmacyclics, AbbVie, Seattle Genetics, Genentech, Novartis, Infinity Pharmaceuticals, Janssen, Merck, TG Therapeutics, MorphoSys, AstraZeneca, BeiGene, MEI Pharma, Bristol Myers Squibb/Celgene, BayerResearch Funding: Pharmacyclics, AstraZeneca Connie L. BatleviStock and Other Ownership Interests: Moderna Therapeutics, Novavax, Pfizer, Bristol Myers Squibb, Regeneron, ViatrisHonoraria: DAVAOncologyConsulting or Advisory Role: Lifesci Capital, GLG, Juno Therapeutics, Celgene, Seattle Genetics, Kite, a Gilead company, TG Therapeutics, Karyopharm TherapeuticsResearch Funding: Janssen Biotech, Novartis, Epizyme, Xynomic Pharma, Bayer, Roche, AutolusOpen Payments Link: https://openpaymentsdata.cms.gov/physician/2778694 Philip CaronStock and Other Ownership Interests: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Johnson & Johnson/Janssen, Novartis, Pfizer, Teva Louis S. ConstineHonoraria: UpToDate, Springer, Lippincott Savita V. DandapaniResearch Funding: Bayer Pamela DrullinskyResearch Funding: Novartis Jonathan W. FriedbergConsulting or Advisory Role: Astellas Pharma, NovartisResearch Funding: Seattle GeneticsPatents, Royalties, Other Intellectual Property: Patent on bone marrow microenvironment signals Paul A. HamlinConsulting or Advisory Role: Juno Therapeutics, Karyopharm Therapeutics, Celgene, Sandoz, AstraZeneca/MerckResearch Funding: Spectrum Pharmaceuticals, Seattle Genetics, Janssen, Portola Pharmaceuticals, GlaxoSmithKline, Molecular Templates, Incyte Richard T. HoppeStock and Other Ownership Interests: Johnson & Johnson, Pfizer Steven M. HorwitzConsulting or Advisory Role: Celgene, Millennium, Kyowa Hakko Kirin, Seattle Genetics, ADC Therapeutics, Portola Pharmaceuticals, Verastem, Takeda, Astex Pharmaceuticals, Kura Oncology, Acrotech Biopharma, C4 Therapeutics, Janssen Oncology, Trillium Therapeutics, Vividion Therapeutics, Myeloid Therapeutics, Ono PharmaceuticalResearch Funding: Celgene, Seattle Genetics, Takeda, Kyowa Hakko Kirin, Aileron Therapeutics, ADC Therapeutics, Verastem, Forty Seven, Trillium Therapeutics, Daiichi Sankyo, Affimed Therapeutics, Corvus Pharmaceuticals Niloufer KhanResearch Funding: Seattle Genetics Matthew J. MatasarStock and Other Ownership Interests: MerckHonoraria: Genentech, Roche, GlaxoSmithKline, Bayer, Pharmacyclics, Janssen, Seattle Genetics, Takeda, IGM Biosciences, ImmunovaccineConsulting or Advisory Role: Genentech, Bayer, Merck, Juno Therapeutics, Roche, Teva, Rocket Medical, Seattle Genetics, Daiichi Sankyo, TakedaResearch Funding: Genentech, Roche, GlaxoSmithKline, Bayer, Pharmacyclics, Janssen, Rocket Medical, Seattle Genetics, Immunovaccine, IGM BiosciencesTravel, Accommodations, Expenses: Genentech, Roche, Seattle Genetics, Bayer Alison J. MoskowitzHonoraria: Seattle GeneticsConsulting or Advisory Role: Seattle Genetics, Takeda, Imbrium Therapeutics, Merck, Janpix, Kyowa Kirin International, miRagen, ADC Therapeutics, Bristol Myers SquibbResearch Funding: Incyte, Seattle Genetics, Merck, Bristol Myers Squibb, miRagen, ADC Therapeutics Ariela NoyConsulting or Advisory Role: MorphoSys, Janssen Biotech, Prime OncologyResearch Funding: Pharmacyclics, Rafael PharmaceuticalsTravel, Accommodations, Expenses: Pharmacyclics, Janssen Oncology Maria Lia PalombaStock and Other Ownership Interests: Seres TherapeuticsHonoraria: Merck, Celgene, Pharmacyclics, Flagship Biosciences, Novartis, Evelo Therapeutics, Jazz Pharmaceuticals, Therakos, Amgen, Seres TherapeuticsConsulting or Advisory Role: Merck, Celgene, Flagship Biosciences, Novartis, Evelo Therapeutics, Jazz Pharmaceuticals, Therakos, Amgen, Seres Therapeutics, Kite, Gilead Company, NovartisResearch Funding: Seres TherapeuticsPatents, Royalties, Other Intellectual Property: Intellectual Property Rights, Juno intellectual property rights David J. StrausConsulting or Advisory Role: Takeda, Seattle Genetics Anas YounesEmployment: AstraZenecaStock and Other Ownership Interests: AstraZenecaHonoraria: Merck, Roche, Takeda, Janssen, AbbVie, Curis, EpizymeConsulting or Advisory Role: Bio-Path Holdings Inc, Xynomic Pharma, Epizyme, Roche, Celgene, HCMResearch Funding: Janssen, Curis, Roche, Genentech, Merck, Bristol Myers Squibb, SyndaxOther Relationship: AstraZeneca Andrew D. ZelenetzHonoraria: NCCN, Clinical Care Options, Oncology Information Group, PER, PlexusConsulting or Advisory Role: Gilead Sciences, Amgen, Genentech/Roche, Celgene, AstraZeneca, DAVAOncology, MorphoSys, BeiGene, MEI Pharma, Vaniam Group, Verastem, Pharmacyclics, Karyopharm Therapeutics, Debiopharm Group, Seattle Genetics, Quant Health Ltd, Kite, Gilead Company, Curis, Coherus Biosciences, Juno/Celgene/Bristol Myers Squibb, Curio ScienceResearch Funding: Genentech/Roche, Gilead Sciences, MEI Pharma, BeiGene Craig H. MoskowitzConsulting or Advisory Role: Merck Sharp & Dohme, Molecular Templates, Takeda, AstraZeneca, IncyteResearch Funding: AstraZeneca, Merck Sharp & DohmeNo other potential conflicts of interest were reported.

Purpose: Cancer classification is foundational for patient care and oncology research. Systems such as International Classification of Diseases for Oncology (ICD-O), Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT), and National Cancer Institute Thesaurus (NCIt) provide large sets of cancer classification terminologies but they lack a dynamic modernized cancer classification platform that addresses the fast-evolving needs in clinical reporting of genomic sequencing results and associated oncology research., Methods: To meet these needs, we have developed OncoTree, an open-source cancer classification system. It is maintained by a cross-institutional committee of oncologists, pathologists, scientists, and engineers, accessible via an open-source Web user interface and an application programming interface., Results: OncoTree currently includes 868 tumor types across 32 organ sites. OncoTree has been adopted as the tumor classification system for American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE), a large genomic and clinical data-sharing consortium, and for clinical molecular testing efforts at Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute. It is also used by precision oncology tools such as OncoKB and cBioPortal for Cancer Genomics., Conclusion: OncoTree is a dynamic and flexible community-driven cancer classification platform encompassing rare and common cancers that provides clinically relevant and appropriately granular cancer classification for clinical decision support systems and oncology research.

Purpose: To evaluate safety and efficacy outcomes for subjects on the ECHELON-1 study treated in North America (NA)., Patients and Methods: ECHELON-1 is a global, open-label, randomized phase III study comparing doxorubicin, vinblastine, and dacarbazine in combination with brentuximab vedotin (A+AVD) versus ABVD (AVD + bleomycin) as first-line therapy in subjects with stage III or IV classical Hodgkin lymphoma (cHL; NCT01712490). Subjects were randomized 1:1 to receive A+AVD or ABVD intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles., Results: The NA subgroup consisted of 497 subjects in the A+AVD ( n = 250) and ABVD ( n = 247) arms. Similar to the primary analysis based on the intent-to-treat population, the primary endpoint [modified progression-free survival (PFS) per independent review] demonstrated an improvement among subjects who received A+AVD compared with ABVD (HR = 0.60; P = 0.012). For PFS, the risk of progression or death was also reduced (HR = 0.50; P = 0.002). Subsequent anticancer therapies were lower in the A+AVD arm. Grade 3 or 4 adverse events (AEs) were more common, but there were fewer study discontinuations due to AEs in the A+AVD arm as compared with ABVD. Noted differences between arms included higher rates of febrile neutropenia (20% vs. 9%) and peripheral neuropathy (80% vs. 56%), but lower rates of pulmonary toxicity (3% vs. 10%) in subjects treated with A+AVD versus ABVD., Conclusions: The efficacy benefit and manageable toxicity profile observed in the NA subgroup of ECHELON-1 support A+AVD as a frontline treatment option for patients with stage III or IV cHL., (©2019 American Association for Cancer Research.)

This topic addresses the treatment of newly diagnosed patients with favorable prognosis stage I and II Hodgkin lymphoma. In most cases, combined modality therapy (chemotherapy followed by involved site radiation therapy) constitutes the current standard of care. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. By combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the appropriate use of combined modality therapy for favorable prognosis stage I and II Hodgkin lymphoma. Increasing information about the late effects of treatment has led to attempts to decrease toxicity by using less chemotherapy (decreased duration and/or intensity or different agents) and less radiation therapy (reduced volume and/or dose) while maintaining excellent efficacy.