NEJM This Week — May 8, 2025

Summary

In this episode of the New England Journal of Medicine, Dr. Michael Beerer discusses several groundbreaking medical advancements and studies. Key topics include the efficacy of daratumumab for high-risk smoldering multiple myeloma, the disappointing results of BCG revaccination for tuberculosis prevention, and the potential of automated insulin delivery for type 2 diabetes. Other highlights include a new hypertension treatment, advancements in CAR T-cell therapy for lymphoma, and the complex chemistry of food in disease prevention. The episode also touches on challenges in primary care, foreign assistance, and the emotional weight of healthcare decisions.

Takeaways

• 😀 Daratumab monotherapy significantly reduces the risk of progression to active multiple myeloma in high-risk smoldering myeloma patients.
• 😀 BCG revaccination failed to provide protection against sustained tuberculosis infection in adolescents, showing no increase in interferon gamma release assay reversion.
• 😀 A 13-week trial on automated insulin delivery in type 2 diabetes demonstrated a significant reduction in glycated hemoglobin levels compared to traditional insulin delivery methods.
• 😀 Laurandrostat, a selective aldosterone synthase inhibitor, showed efficacy in reducing blood pressure in patients with uncontrolled, treatment-resistant hypertension.
• 😀 Enhanced CAR T-cell therapy targeting CD19 showed promising results in treating relapsed or refractory lymphoma after previous CAR T-cell therapy failures.
• 😀 Poor nutrition is a leading cause of preventable diseases in the U.S., and dietary quality plays a crucial role in disease prevention and management.
• 😀 A 70-year-old man’s case of weight loss, weakness, and anorexia required iterative clinical reasoning to diagnose his condition, demonstrating the complexity of diagnosing rare conditions.
• 😀 The dismantling of U.S. foreign assistance programs threatens global health progress, requiring advocacy from clinicians and scientists to ensure continued support for global health.
• 😀 Primary care physicians face an increasing burden of non-clinical administrative demands, which detracts from patient care and adds to clinician stress.
• 😀 A perspective on DIPG treatment shows the emotional challenges clinicians face when balancing hope and realism for terminal patients, highlighting the complexities of delivering end-of-life care.

Q & A

What was the main conclusion of the phase 3 trial on daratumab for high-risk smoldering multiple myeloma?

The phase 3 trial found that subcutaneous daratumab monotherapy significantly lowered the risk of progression to active multiple myeloma or death and led to higher overall survival compared to active monitoring, with no unexpected safety concerns.

How did BCG revaccination perform in the prevention of tuberculosis infection in the phase 2B trial?

The phase 2B trial showed that BCG revaccination did not provide protection against sustained MTB infection in QFT test negative HIV-negative adolescents, failing to meet its primary endpoint.

What were the results of the study on automated insulin delivery in type 2 diabetes?

The study on automated insulin delivery found that patients using the system experienced a significantly greater reduction in glycated hemoglobin levels compared to those using traditional insulin delivery methods. Hypoglycemia rates remained low in both groups.

What were the findings regarding laurandrostat's efficacy in patients with uncontrolled hypertension?

Laurandrostat was associated with greater reductions in 24-hour average blood pressure than placebo in patients with uncontrolled and treatment-resistant hypertension, though there was a small increase in potassium levels.

What did the trial on enhanced CAR T-cell therapy for lymphoma reveal?

The trial on enhanced CAR T-cell therapy showed promising results, with 81% of patients experiencing a complete or partial response and 52% achieving a complete response after treatment with the anti-CD19 CAR T-cell product.

What is the significance of the review article on the chemistry of food in relation to health?

The review article highlights the complexity of food's chemical composition and its implications for health, emphasizing how diet can influence the prevention of diseases such as cardiovascular disease, type 2 diabetes, and cancer.

What was the initial diagnosis of the 70-year-old man with weight loss, weakness, and anorexia in the case report?

The initial diagnosis was an indeterminate adrenal nodule after a CT scan, though further complications and diagnostic uncertainty arose as his symptoms progressed, leading to a more complex diagnosis process.

What concerns are raised about the Trump administration's cuts to foreign assistance programs in the perspective article?

The article expresses concern that the cuts to foreign assistance programs undermine global health efforts and may negatively impact populations both abroad and in the U.S. It also discusses the importance of advocacy for continued U.S. engagement in global health.

What is the primary challenge faced by primary care physicians as described in the article on non-clinical demands?

Primary care physicians are increasingly burdened by administrative tasks, which detract from their ability to focus on direct patient care. The article advocates for streamlining these administrative processes and providing compensation for the additional work.

What is the significance of the perspective article titled 'The Last Dose' about a patient with diffuse intrinsic pontine glioma (DIPG)?

The article discusses the emotional and professional challenges faced by clinicians when dealing with terminally ill patients, particularly those with DIPG, highlighting the tension between maintaining hope for patients and confronting the harsh realities of prognosis.