An opinionated take on NEJM highlights for May 2019


TAVR for all?

TAVR has become the standard of care for patients who need an aortic value replacement but are at high/medium surgical risk.  But what about those at low-risk? Two studies answer that question, one with the Edwards device and the other with Medtronics. Both show that TAVR is superior along a number of end-points (stroke, hospitalization duration, atrial fibrillation) both at 30 days and at 1-2 year. Long-term outcomes remain a question though. Low-risk patients are younger (mean age 73-74) and will live with their valves longer, which means that in contrast with the mechanical valves that can be implanted surgically, they will wear out in a sizable number of patients who survive past the expected 10-year service-life. What will happen is suggested by a letter describing an early recipient of TAVR in 2008: her original TAVR-device wore out, but the interventional cardiologists simply put a new device inside the old one (a TAVR inside a TAVR) and the patient did well.  A collateral effect may also be that the contraction of cardiac surgery as a sub-specialty will continue – as coronary heart disease and aortic valve disease are increasingly treated by interventional cardiologists instead of heart surgeons, fewer centers will have the scale to maintain a cardiac surgery programs of sufficiently volume to ensure quality. Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients; Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk PatientsInformed Shared Decisions for Patients with Aortic Stenosis; Transcatheter Aortic-Valve Replacement — 10 Years Later (subscriber access)


Getting closer in multiple myeloma

For multiple myeloma (MM) patients, this must be a time of intense hope and fear – hope that for the first time a potential cure is within the horizon of usual survival duration for MM, fear that they will miss the window by a couple years or even months.   Bluebird/Celgene report on their experience with the first 33 MM patients receiving their autologous CAR-T therapy targeting BCMA (B-cell maturing antigen) known as bb2121. All patients had previously received at least three lines of therapy. There was a clear dose-response relationship and in the higher dose groups, several cases of long-term complete responses which might represent cures. I now have no doubt that with the right cocktail of antigens and preparatory regimen, this approach will eventually be made to work for most patients.  One key question is that this is now being tested in very advanced disease, but the optimal timing for CAR-T therapy may be much earlier. If so, there is a big pipeline of drugs in MM that may become less relevant. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma (subscriber access)


The road to precision medicine in breast cancer

The first important molecular segmentation of breast cancer appeared a generation ago with description of the estrogen receptor and progesterone receptor status (ER and PR, and combined status sometime referred to as HR) – these markers had clear implications in directing treatment around the use of hormonal therapy. Then, twenty years ago another key molecular marker emerged in the form of HER2/neu, previously a poor prognostic indicator, but one that predicts response to trastuzumab (Herceptin). Since then, these three markers have been the key drivers of how we think of breast cancer in general, with monikers such as “triple negative” to describe patients with none of these markers. Now we may have to add a fourth one to the mix: PIK3CA.  A study of the PI3Kalpha inhibitor alpelisib (Piqray, Novartis, just approved) in advanced breast HR+ cancer showing that it prolongs progression free survival from 6 to 11 months in patients with the PIK3CA mutations (about 40% of HR+ breast cancers) but has no effect in those without those mutations.   It took 40 years to get to 4 key markers for breast cancer therapy, my guess is that by the end of the next decade, we will be well into the double digit numbers.  Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer (subscriber access)


The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.