Polatuzumab for Follicular Lymphoma

A recent article in The Lancet Haematology reported the results of a phase 2 clinical trial for two Antibody–drug conjugates (or ADC).

An Antibody-drug conjugate is kind of a step up from monoclonal antibodies like Rituxan, because it uses what's great about a monoclonal antobody (it can seek out a protein on a cancer cell), but also adds something to the party. The "conjugate" is an add-on, in this case, a treatment that can mess with the cancer cell. So the antibody part of the conjugate finds the cancer cell, and then the targeted treatment part of the conjugate gets into the cell and does some work to kill the cell.

ADCs are a great idea, but also complicated. They have three parts that all need to work well: the antobody that targets the cell, the treatment that kills the cell, but also the link that holds them together. But if it does all work well, then ideally you have a very targeted treatment -- unilke traditional chemo, the treatment is delivered right to the cancer cell, rather than getting to lots of healthy cells as well.

The article is called "Polatuzumab Vedotin or Pinatuzumab Vedotin Plus Rituximab in Patients with Relapsed or Refractory Non-Hodgkin Lymphoma: Final Results from a Phase 2 Randomised Study (ROMULUS)."

In the study, researchers compared two ADCs plus Rituxan, with half of the patients getting the ADC called Polatuzuman Vedotin and the other half Pinatuzumab Vedotin. To make it easier, the authors very kindly call them R-Pola and R-Pina. Some patients in the study had Follicualr Lymphoma, and some had Diffuse Large B Cell Lymphoma, FL's more aggressive cousin. All of the patients were Relapsed or Refractory -- their last treatment had stopped working.

R--Pola worked better than R-Pina.

42 patients with DLBCL received R-Pina, with 60% achieving a response, with 26% a Complete Response. 39 had R-Pola, with 54% getting a response (26% a CR).
For the Follicular Lymphoma group, 62% had a response to R-Pina (5% a CR). For R-Pola, 70% had a response, with 45% getting a CR.

Side effects were common for all groups, with 62% of the FL group getting fairly serious side effects from R-Pina, 50% for R-Pola. Side effects included infections, nerve issues, and blood cell problems.

In the end, the researchers are recommending further research on R-Pola, but not R-Pina. The responses lasted longer for R-Pola, and the seriousness of side effects seemed to outweigh the benefits for R-Pina.

So we can probably expect to see more from Polatuzumab Vedotin. The antibody part of ADC works by targeting CD79b, a protein that is found on B-cell lymphocytes. (Rituxan targets CD22, in case you wated a comparison). The anti-cancer part of the ADC is called Monomethyl auristatin E, or MMAE. It's an antimitotic, which means it stops mitosis, the process that cells use to divide and create more cells. So it keeps the cancer cell from growing into more cancer cells.

 Polatuzumab Vedotin was given Priority Review designation a couple of months ago when used in combination with Bendamustine and Rituxan for Relapsed or Refractory DLBCL. It's in a bunch of other clinical trails, in various combinations, against a few different types of blood cancers. We'll be hearing more about it soon, I'm sure.

Definitely one to keep an eye on.