ASH: Obinutuzumab (Two Studies)

Continuing with ASH commentary:

There are two sessions that will present results from the GALLIUM study, which looked at Obinutuzumab (also known as GA101 and Gazyva) plus chemotherapy as a first treatment for indolent lymphoma patients, comparing it to Rituxan + chemo.

Obinutuzumabis an anti-CD20 monoclonal antibody, like Rituxan. But it has been created differently. First, it is humanized, meaning it is created from  human cells (Rituxan has some mouse parts in it  -- sorry, some murine components). Some think humanized anibodies will cut down on the allergic reactions that Rituxan sometimes brings on (as it did for me). Obinutuzumabis also glycoengineered. Basically, it was made to have more sugar-related enzymes, which allows it to signal some T cells that will find and kill the cancer cells. There's more to it than that, but the bottom line is, Obinutuzumabwas created so it would be like Rituxan, but more effective.

The two studies from ASH focus on Follicular Lymphoma patients from the GALLIUM study (which is a phase 3 clinical trial that involves patients from several different countries).

The first one is called "Obinutuzumab-Based Induction and Maintenance Prolongs Progression-Free Survival (PFS) in Patients with Previously Untreated Follicular Lymphoma: Primary Results of the Randomized Phase 3 GALLIUM Study." (This was selected for the "Plenary Scientific Session," which makes it one of the top six presentations in the whole conference. A big deal.) The study compared Rituxan + chemo + R-maintenance with Obinutuzumab + chemo + Obinutuzumab maintenance. So we have a direct comparison between the two anti-CD20 treatments. The way of comparing was Progression-Free Survival (PFS) -- which treatment allowed patients to go longest without having their FL get worse?

The study is still going on, with not enough patients having reached the median yet (that's a good thing), but the researchers assume that the Obinutuzumab group has a PFS about 1.5 times longer than the Rituxan group, which could be as much as 3 years of Progression Free Survival. That's pretty significant (and the ASH Selection Committee giving the session a place of honor would seem to be saying the same thing). It's been tough to find something that works better than Rituxan. This might be it (when it combined with chemo -- either Bendamustine, CHOP, or CVP) and followed with maintenance. The researchers suggest this should be a new standard of care.

The other study involving Obinutuzumab and the GALLIUM study is "Minimal Residual Disease in Patients with Follicular Lymphoma Treated with Obinutuzumab or Rituximab As First-Line Induction Immunochemotherapy and Maintenance in the Phase 3 GALLIUM Study." This one uses the same patients to argue that Minimal Residual Disease (MRD) is a way ti measure how effective a treatment has been. Basically, by figuring out whether or not the treatment has cleaned up all of the cancer cells, we can tell how likely it is that the cancer will return.

To find MRD, researchers looked at either blood samples of bone marrow samples to see if there were any genetic markers on cells that would show that they were FL cells. The samples were taken at the mid-point of the treatment and at the end of the treatment (remember, this is still the GALLIUM study, so patients had either Obinutuzumabor Rituxan + chemo + maintenance). The tests that looked for genetic markers are sensitive enough that the researchers could be sure that the disease was present. (Compare this to something like a PET scan as a way of measuring how well a treatment worked. A scan might not light up, but there might be a small number of cancer cells still hanging around -- too small to light up a scan, but not too small that they won't multiply and bring the disease back. It's a more effective way of measuring success.) So there were really two things being measured here. First, the study showed that MRD was a good way of measuring how successful a treatment could be. And second, because they measured for MRD at the mid-point and the end, that showed that Obinutuzumab was more successful than Rituxan at clearing out cancer cells quickly.

Together, the two studies show that Obinutuzumab is really good when it is combined with chemo and followed with maintenance. It might be a good replacement for Rituxan in that situation. The same combo was already approved earlier this year as a second-line treatment for patients who already had Rituxan as part of their first treatment. It will be interesting to see what other combinations show positive results from here.