NEJM Group

Most patients with newly diagnosed chronic myeloid leukemia (CML) are treated with one of four approved ATP-competitive tyrosine kinase inhibitors (TKIs): first-generation imatinib or second-generation nilotinib, dasatinib, or bosutinib.     However, many patients switch treatments within the first year because of troublesome adverse effects.    In the ASC4FIRST trial, researchers assessed the efficacy and safety of asciminib as compared with investigator-selected TKIs in patients with newly diagnosed CML.     405 patients were randomly assigned to receive either asciminib or an investigator-selected TKI: imatinib, nilotinib, dasatinib, or bosutinib. The two primary objectives of the trial were to compare the efficacy of asciminib with that of the investigator-selected TKIs considered together and with imatinib considered individually.     The primary end point for both objectives was major molecular response (defined by BCR::ABL1 transcript levels ≤0.1% on the International Scale) at week 48.    Asciminib showed superior efficacy and a favorable safety profile as compared with investigator-selected TKIs considered together, and with imatinib individually, in patients with newly diagnosed chronic myeloid leukemia. Whether asciminib is more effective than the second-generation TKIs is not clear.    Read the full ASC4FIRST trial results and Plain Language Summary: https://nej.md/4bNNr3c    #ClinicalTrials #MedicalResearch 

#ESMO24 Round Up: 11 articles were simultaneously published in NEJM and presented at this year’s ESMO - European Society for Medical Oncology Congress in Barcelona, Spain. Most of the articles included a podcast with NEJM Group editors discussing the significance of the trial results.     Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer (ADRIATIC)   📄 Full article: https://nej.md/4d0eZ5m    Pembrolizumab in HER2-Positive Gastric Cancer (KEYNOTE-811)  📄 Full article: https://nej.md/47BTmYp  🎧 Podcast: https://nej.md/3MKJrWw    Preoperative Chemoradiotherapy for Resectable Gastric Cancer (TOPGEAR)  📄 Full article: https://nej.md/4gg4gqv  🎧 Podcast: https://nej.md/4elNDb7    Ponsegromab for the Treatment of Cancer Cachexia  📄 Full article: https://nej.md/3XE645a  🎧 Podcast: https://nej.md/3zsPNXw    Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma (AMBASSADOR)  📄 Full article: https://nej.md/4gh1b9D  🎧 Podcast: https://nej.md/4go9Eb5    Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer (DESTINY-Breast06)  📄 Full article: https://nej.md/3TovTE9  🎧 Podcast: https://nej.md/3XHT4LS    Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma (CheckMate 067)  📄 Full article: https://nej.md/4dUqm0g  🎧 Podcast: https://nej.md/4gkKjPj    Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer (NIAGARA)  📄 Full article: https://nej.md/4gmAqk3  🎧 Podcast: https://nej.md/4e2bo8g    Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer (KEYNOTE-522)  📄 Full article: https://nej.md/3XzBOIS  🎧 Podcast: https://nej.md/4d3VCIV    Zolbetuximab in Gastric or Gastroesophageal Junction Adenocarcinoma   📄 Full article: https://nej.md/3ML9dtK  🎧 Podcast: https://nej.md/4dX7X2X    Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors (CABINET)   📄 Full article: https://nej.md/3AYuEoI  🎧 Podcast: https://nej.md/3ZFER3R 

Our October 2024 issue, guest edited by Rasu Shrestha MD MBA, is specially themed around digital health technology innovation: digital technology adoption, the uses of artificial intelligence, in-basket workflow, telehealth-enabled nursing, and digitally enabled care. 📖 View the issue: https://nej.md/3zjbwRS 🎧 Read or listen to the guest editor's letter: The Ongoing Challenge of Digital Technology Innovation: https://nej.md/47yfEKj 💻 Insights Report: Cautious Embrace of Digital Technologies for Health Care: https://nej.md/47rEbk8 with expert advisor Rasu Shrestha MD MBA Advocate Health 📧 In Depth: The “Inboxologist” — A Novel Approach to In-Basket Management in Primary Care: https://nej.md/3B5rLSZ 👨⚕️ Case Study: Virtual Nursing to Improve Patient and Team Member Experiences at NewYork-Presbyterian Hospital: https://nej.md/3B2mDyW 📈 Article: Standing on FURM Ground: A Framework for Evaluating Fair, Useful, and Reliable AI Models in Health Care Systems: https://nej.md/3zeENgn 📉 Article: Reducing Fraud, Waste, and Abuse Through Real-Time AI-Based Screening: Prospective Results in Deployment: https://nej.md/3zx76Xv 🤝 Commentary: The Digitally Enabled Care Framework: Leveraging Technology to Enhance the Physician–Patient Relationship: https://nej.md/3MKZ5l1 📺 Free Web event: Don't forget to tune into our gen AI and health IT event today or watch the recording after! https://nej.md/3M7HLWI #HealthIT #DigitalHealth #HealthCareAI #HealthCareDelivery #HealthCareInnovation

Primary central nervous system (CNS) vasculitis, also known as primary angiitis of the CNS, is a rare form of vasculitis that is limited to the brain and spinal cord and causes a variety of neurologic syndromes. Because of its rarity and the similarity of some of these syndromes to more common disorders, primary CNS vasculitis is often misidentified. Descriptions of this condition date back only to the mid-1950s. Primary CNS vasculitis may occur in children, although this is uncommon. In a new review, the authors focus on the disorder in adults.    Continue reading the Review Article “Primary Central Nervous System Vasculitis” by Carlo Salvarani, MD, Gene G. Hunder, MD, and Robert D. Brown, Jr., MD, MPH, from Mayo Clinic, Azienda Ospedaliera–IRCCS di Reggio Emilia, and Università degli Studi di Modena e Reggio Emilia: https://nej.md/3BaqxGh 

The 2024 Lasker–DeBakey Clinical Medical Research Award recognizes Drs. Habener, Mojsov, and Knudsen, who developed GLP-1 medicines that have revolutionized the treatment of obesity.    Figure 1 from the article illustrates the derivation of glucagon-like peptide-1 (GLP-1) and the biologic actions of GLP-1 medicines.    As shown in Panel A, the mammalian proglucagon-derived peptides are derived by means of post-translational processing from a larger proglucagon precursor encoded by GCG. Glucagon is synthesized in and secreted from the endocrine pancreas, whereas biologically active GLP-1(7–37) and GLP-1(7–36)amide, together with several structurally related proglucagon-derived peptides — principally glicentin, oxyntomodulin, GLP-1, and glucagon-like peptide-2 (GLP-2) — are synthesized by gut endocrine cells and secreted into the circulation. Proglucagon-derived peptides are also produced within brain-stem neurons. As shown in Panel B, GLP-1 medicines pharmacologically mimic the actions of native GLP-1 and produce multiple metabolic benefits. These actions include a reduction in the incidence of obesity-associated complications, often independent of weight loss. The abbreviation γGlu denotes γ-glutamate, DDP-4 dipeptidyl peptidase 4, and mRNA messenger RNA.    Read the Clinical Implications of Basic Research article “Discovery of GLP-1–Based Drugs for the Treatment of Obesity” by Daniel J. Drucker, MD, from the Mount Sinai Health System and the University of Toronto: https://nej.md/3XOepUg 

Severe chronic graft-versus-host disease (GVHD) is a serious long-term complication that can occur after allogeneic hematopoietic stem-cell transplantation (HSCT). The first-line treatment of newly diagnosed chronic GVHD is glucocorticoids. However, some patients do not have a response to glucocorticoids, or they become glucocorticoid-dependent. Standard treatments for refractory or recurrent chronic GVHD have not been established. The three drugs currently approved by the Food and Drug Administration (FDA) for refractory chronic GVHD (ibrutinib, ruxolitinib, and belumosudil) do not act on all manifestations of chronic GVHD. Of interest, then, is a report in NEJM by Wolff et al., who examined the effects of axatilimab, a humanized antibody that targets the colony-stimulating factor 1 receptor (CSF1R), in patients with recurrent or refractory chronic GVHD.     An editorial describes the science behind a study of axatilimab to treat chronic graft-versus-host disease.    Read the editorial “CSF1R Blockade for Refractory Chronic Graft-versus-Host Disease” by Mohamad Mohty, MD, PhD, from Sorbonne Université, INSERM, CRSA PARIS, and Greater Paris University Hospitals - AP-HP: https://nej.md/3MOORQs    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚  📄 Original Article by D. Wolff et al.: Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease https://nej.md/3Zpi8sw  📄 Editorial by Stefanie Sarantopoulos, MD, PhD: Targeting CSF1R in Chronic GVHD — Lessons in Translation https://nej.md/4etpTlC  

Physicians have long warned that “patients don’t read the textbook” — that neither patients nor diseases always behave as described in reference texts, write the authors of a new Perspective. Yet even as they have debated the uses and limits of texts, physicians have relied on reference tools for centuries as repositories of knowledge. The doctor’s proverbial “peripheral brain” has taken on various forms, from textbooks and reference files to pocket guides and smartphones. Tracing the form and function of the peripheral brain in medicine illustrates the enduring yet evolving influence of reference tools on physician identity, thinking, and practice.    Continue reading “Centering the Peripheral Brain — The History of Reference Tools in Medicine,” the latest Perspective in the History of Medicine series, by Andrew Lea, MD, DPhil, and Scott H. Podolsky, MD, from Brigham and Women's Hospital and Harvard Medical School: https://nej.md/3Zei5iZ 

There are more than 20 types of epithelial and nonepithelial pancreatic cysts, but the majority belong to the six most common histologic categories. The two most prevalent benign lesions, pseudocysts and serous cystadenomas, account for 15 to 25% of all pancreatic cysts. The two types of mucinous cysts, intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), are the predominant premalignant cystic lesions and account for approximately 50% of cysts that are found incidentally on imaging for other indications. Solid pseudopapillary neoplasms and cystic pancreatic neuroendocrine tumors are two less common malignant cystic neoplasms. Figure 1 (shown) provides an overview of the characteristics of pancreatic cysts and the associated risk of cancer.    Learn more in the Review Article “Pancreatic Cysts” by Tamas A. Gonda, MD, Djuna L. Cahen, MD, PhD, and James Farrell, MD, from NYU Langone Health, Erasmus MC, Yale School of Medicine, and Yale New Haven Health: https://nej.md/4g4jz5s  

Locally advanced or metastatic leiomyosarcoma carries a bleak prognosis. Doxorubicin monotherapy has been the standard first-line therapy for 50 years, but combination therapy with trabectedin showed promising results in a phase 2 trial. Additional data are needed.     In the LMS04 trial, researchers examined the efficacy and safety of doxorubicin plus trabectedin followed by trabectedin maintenance, as compared with doxorubicin alone, as first-line therapy for patients with metastatic or unresectable leiomyosarcoma.      Patients with untreated locally advanced or metastatic leiomyosarcoma were assigned to receive either doxorubicin alone or doxorubicin plus trabectedin, with trabectedin continued as maintenance therapy in patients in the doxorubicin–trabectedin group who did not have disease progression. Posttreatment surgery for residual disease was allowed.     Results for progression-free survival (the primary end point) were reported previously. The current analysis reports on overall survival and extends follow-up for progression-free survival.     Among patients with metastatic or surgically unresectable uterine or soft-tissue leiomyosarcoma, first-line treatment with doxorubicin–trabectedin followed by trabectedin maintenance was associated with improved overall survival and progression-free survival, as compared with doxorubicin alone.     Read the full LMS04 trial results and Plain Language Summary: https://nej.md/3Xa9oDT     #ClinicalTrials #MedicalResearch 

𝗩𝗗𝗝 𝗿𝗲𝗰𝗼𝗺𝗯𝗶𝗻𝗮𝘁𝗶𝗼𝗻 is a process involving the cutting and rejoining of the loci encoding T-cell and B-cell receptors. These loci are highly polymorphic and contain multiple variable (V), diversity (D), and joining (J) regions, flanked by recombination signal sequences (RSS). Each developing T and B cell rearranges the locus to generate a unique transcript containing one V, one D, and one J region, a process known as VDJ recombination. The RAG1–RAG2 protein complex begins this process by cutting at RSS sites. More about this NEJM Illustrated Glossary term in comments.    To learn more about this NEJM Illustrated Glossary term, read “Gene Therapy for Artemis-Deficient SCID” by Sung-Yun Pai, MD, from the National Cancer Institute (NCI): https://nej.md/3Yzc3Hf       Explore more terms: https://nej.md/glossary