Sunday, December 20, 2015

ASH: Ofatumumab

Still looking at some of the research that was presented at ASH this year.

This one is called "Phase II Trial of Ofatumumab (OFA) in Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL): CALGB 50901 (Alliance)."It looks at Ofatumumab as a first treatment for Follicular Lymphoma.

Ofatumumab is a lot like Rituxan -- a monoclonal antibody that targets the protein CD20 on the surface of B cells. The key difference is that Ofatumumab fully humanized. Rituxan was developed using mouse cells, but Ofatumumab was developed using human cells. The thinking is that this might cut down on some of the allergic reactions that people have when they are first given Rituxan. (I had chills and a lot of itching.)

In the ASH study, the researchers try to compare Ofatumumab to Rituxan in patients who haven't been treated yet and who have low or intermediate risk FL. Since this is a comparison to Rituxan, they were looking to show that Ofatumumab would do a better job than Rituxan, so they considered a repsonse rate below 60% to essentially be a failure, and over 80% to be a great success.

Since it was a phase II study, it was fairly small, with just 51 patients. Some received a dose of 500mg, and others 1000mg, all once a week for four weeks, and then four more times every 8 weeks. For the patients with the 1000mg dose, the Overall Response Rate was 86.7%, and 1 year Progression Free Survival was almost 100%. For the patients with the 500mg dose, the OR was 60%, and the 1 year PFS was 85.1%.

The researchers conclude that Ofatumumab was effective and well-tolerated. The side effects were not too far out of line with Rituxan. However, they also concluded that  "Activity appears to be in a range comparable to that reported with other anti-CD20 antibodies in this setting, suggesting that significant improvements in efficacy will require novel combinations." In other words, it did about as well as Rituxan, but not much better than Rituxan, so it seems unlikely to replace it. Maybe it will be used with some other treatments in ways that are more effective than Rituxan.

Ofatumumab isn't the first attempt to replace Rituxan, and so far, no monoclonal antibody has shown to be better than it. I find that fascinating. There has to be something about the mechanism of monoclonal antibodies that has a limit, which is who combining it with something else might be the way to go. we've known for a long time that Rituxan works well, and CHOP and other chemos work well, but it's when they are put together that they really shine. Research into which combinations work best to attack cancer from different angles seems to be a very effective strategy.

Ofatumumab was actually in the news for something else recently, too. In late November, the company that makes Ofatumumab announced that it was stopping a phase III trial before it was done because the early results showed that it wasn't going to be much of an improvement over Rituxan. This was a little different from the ASH study -- it compared Ofatumumab and Rituxan directly, but involved patients who had previously been treated with Rituxan. But the big picture was still the same thing -- it's hard to do better than Rituxan.

If monoclonal antibodies do have a long-term future in Follicular Lymphoma treatment,  it looks like it will be in combination with other. newer treatments.


Popplepot said...

Merry Christmas Bob and battlers, an uplifting gift just what we need, (Google)
3989 Life Expectancy in Follicular Lymphoma Is Mainly Determined By Response to First LINE Treatment: A LONG-TERM Survey on 597 patients

Rodrigo Carvalho said...

Hi Popplepot
Bob posted that issue two weeks ago.
Merry Xmas