An opinionated take on NEJM highlights for December 2022

An unusual article on road safety

Motor vehicle accidents are a major share of morbidity and mortality in the young, and as such prevention has long been considered a medically adjacent area (e.g. with pediatricians asking about infant car seats etc.).  Still it was a surprise to see an article on an intervention specifically designed to improve road safety in the NEJM, but it applies specifically to teens with an ADHD diagnosis, for whom distraction while driving is a significant risk factor. In the study, 152 teen drivers with ADHD went through a program of computer-based driving simulations: half were trained on a specific module to reduce prolonged glances away from the roadway whereas the other half participated in driving simulations that did not include that training. The drivers were then followed-up for a year with their primary vehicle fitted with a recording system to log collisions and near-collisions. Those teens that were trained had an incident rate that was ~60% of those that were not, an impressive effect. Will it go into broad use? I am not so sure. It appears to be a purely academic effort; absent an entrepreneurial for-profit spirit to push adoption, it may be a long time before we upgrade our driver’s ed process. Trial of Training to Reduce Driver Inattention in Teens with ADHD


A phase 3 with TILs

Well before IO became all the rage, it was clear to pathologists that many cancers trigger a local immune response visible under the microscope as tumor infiltrating lymphocytes (TILs). A number of efforts have been made over the years to harvest, expand, and re-infuse these primed lymphocytes in the hope that this would boost anti-tumor activity, but these have typically been small, almost anecdotal studies. Now a Dutch-Danish academic collaboration reports on the result of a robust phase 3 study comparing autologous TIL therapy with CTLA-4 inhibition in patients with advanced melanoma (most of whom had already failed PD-1 therapy).  It shows a significant PFS advantage in the TIL group, and excitingly, the potential for some patients experiencing true long term remissions (cures?). One question in my head is how should we think of this therapeutic modality? Is this a CAR-T like drug, or is this more like a conditioned bone marrow transplant? Lines are getting blurred, and there is a real risk that this ambiguity may eventually be a brake on innovation and adoption because the regulatory and business models for TILs are ill-defined and therefore there is more risk.  Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma


Briefly noted: more BiTEs

Bispecific alternatives to CAR-T continue to forge ahead with two promising single-arm early stage studies, one in lymphoma and one in multiple myeloma (the latter targeting a new tumor antigen). I am looking forward to an eventual head-to-head trial of CAR-T vs. bispecific (preferably with the same antigen), but fear we may wait a long time. Of note though, is that a third of the patients in the glofitamab lymphoma study had already undergone CAR-T therapy and their response rate was similar to that of the patients who had received other prior therapies.  Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma; Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma


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.