Polatuzumab vedotin just FDA approved for diffuse large cell Non Hodgkin's Lymphoma!

The standard of care for the treatment of aggressive non-Hodgkins lymphoma dating back to the 1970s has been a regimen called CHOP given every three weeks for 6 cycles. Each letter of CHOP stands for a different chemotherapy drug (cyclophosphamide, adriamycin, vincristine, and prednisone). This regimen has been proven so effective that aside from the addition of Rituxan in early 2006, (changing the name to R-CHOP), it has withstood the test of time. It has cured hundreds of thousands of patients with non-Hodgkins lymphoma and has remained the gold standard treatment for decades. Until now. 

In a recent clinical research trial, a new drug, Polatuzumab vedotin (Polivy) was substituted for the drug vincristine in the standard CHOP regimen. Polatuzumab has an interesting mechanism of action. It binds to a protein on the surface of lymphoma cells called CD79b. Following this binding, it is internalized into the cell where the linker is cleaved, releasing a high-potency chemotherapy drug called MMAE into the cell which causes the death of the lymphoma cell. 

In the POLARIX study, RCHOP was compared to the new regimen pola-RCHP with improvement in progression-free survival and event-free survival. This means that as of early in the study more patients who received this drug are alive without lymphoma compared to patients who received the standard treatment. An improvement in complete response rate was not seen, and thus far an improvement in overall survival (an improvement in cure rates) has not been shown. Hopefully, this regimen will eventually show an improvement in the chances of being cured of lymphoma, but the study has not been conducted long enough to answer this question. 

My Rating: 4 out of 5 stars

Polatuzumab can potentially change the standard of care for the treatment of non-Hodgkins lymphoma. As mentioned, above, the standard R-CHOP regimen has largely been unchanged for years. Of course, the addition of this drug to the regimen adds significant cost. An improvement in overall survival (basically, the cure rate) has not been shown thus far. Toxicities in the POLARIX study were similar whether patients received Polatuzumab or not, so it does not appear to make the regimen more toxic. Time will tell if this drug lives up to expectations. The name CHOP was always so gratifying and easy to say, and the acronym conveyed action. It may be hard for my tongue to make the change to pola-R-CHP. If this drug shows a survival benefit, will upgrade to five stars.

Rating Guide 

5 stars: First drug in class/indication with a new mechanism of action, major improvement over existing treatments

4 stars: First drug in class/indication with a new mechanism of action, minor improvement over existing treatments

3 stars:  Additional drug in class/indication, offers some advantages over existing drugs in class 

2 stars:  Additional drug in class/indication, no real advantage over existing drugs

1 star:  Why was this even approved?