A New Cancer Strategy

89468358PD-1 is a cancer pathway that's been known for some time to the cognoscenti.  On PodMed this week, Rick and I talk about a study in NEJM, which is incidentally where all the studies we talk about this week are published, that appears to bring manipulation of this pathway to fruition in folks with Hodgkin's lymphoma. Good news indeed, as well as proof of concept.  What did they do? First, a little background is appropriate.

PD-1, in that often inscrutable scientific fashion that is happily absent here when it comes to naming, stands for programmed death.  In this case it refers to a way our bodies use to damp down an immune response by T cells, one of the army of cells mobilized to protect us but which need to be called off when the deed is done. We can think of PD-1 as running up the surrender flag so T cells chill out.  Turns out cancer cells do the same, running up the surrender flag to call off T cells that might otherwise attack and kill them.  Oh so clever cancer cells!  This property partially explains why our immune systems fail to recognize these invaders and dispatch them, and it's also something researchers have been struggling to exploit for some time.  Indeed, antibodies to manipulate this pathway have been developed and used clinically, with this study reporting such an antibody for Hodgkin's.

Hodgkin's, of course, is rather a curiosity when it comes to immune system manipulation.  The problematic cells in the disease known as 'Reed-Sternberg cells' actually reside within a veritable army of immune cells, yet somehow evade detection and destruction. PD-1 utilization is alive and well in this type of cancer, and the authors reveal that host infection with Epstein-Barr virus also up-regulates this mechanism. Accordingly, 23 patients with Hodgkin's lymphoma who had either relapsed or had refractory disease were enrolled in this study to receive the monoclonal antibody 'nivolumab.' Previous treatment of these folks included some pretty heavy hitting therapy: stem cell transplantation and an antibody 'brentuximab vedotin.'

Here's the good news: "An objective response was reported in 20 patients (87%), including 17% with a complete response and 70% with a partial response; the remaining 3 patients (13%) had stable disease."  Wow!  That's very impressive.  Side effects could be problematic with nivolumab: "Overall, drug-related adverse events were reported in 18 patients (78%). The most common were rash (in 22%) and a decreased platelet count (in 17%). Drug-related grade 3 adverse events, which were reported in 5 patients (22%), included the myelodysplastic syndrome, pancreatitis, pneumonitis, stomatitis, colitis, gastrointestinal inflammation, thrombocytopenia, an increased lipase level, a decreased lymphocyte level, and leukopenia." These drug effects were manageable and the authors conclude that inhibition of the PD-1 pathway may be a very important therapeutic target in patients with this disease, and we agree.  Rick also opines that examination of additional tumor types will likely result in more applications for this strategy.

Other topics this week include the use of progesterone in traumatic brain injury, a new type of blood thinner, and US healthcare and equality, as mentioned before, all in NEJM.  Until next week, y'all live well.

 

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