Wednesday, December 30, 2015

Rituxan Maintenance: Shorter is Better?

The current Journal of Clinical Oncology has the results of a study of Rituxan Maintenance in Follicular Lymphoma. In some ways, the study helps clarify the best way to use Rituxan Maintenance, though it raises some questions as well.

(We wouldn't really expect any kind of clear answer when it comes to treating Follicular Lymphoma, would we?)

The study is published in the article called "Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/0." Medical journal articles are pretty good about using straightforward titles, and this one is no different:

The article reports the results of a phase III clinical trial that looked at short-term and long-term use of Rituxan Maintenance after Rituxan induction therapy. In other words, patients were first given Rituxan for four weeks, and then if it seemed to work, they were split into two groups, with some getting Rituxan Maintenance every two months for 4 doses (or 8 months), and some getting it every two months for up to 5 years (or until they had an event). The measurement here was Event Free Survival (EFS), which is a little less common than many FL trials, which often use Progression Free Survival (which measures the disease getting worse) or Overall Survival (which measures death from any cause). EFS is a little broader, and the "events" can include death or disease progression, but also things like a secondary cancer, unacceptable toxicity, or using other treatments related to cancer.

The authors say that, while there are lots of studies that look at Rituxan Maintenance, those studies use lots of different time periods. Their aim here was to compare two different time periods directly to see which one worked best.

The plan had been to stop the study at about 5 years, with the expectation that there would have been 99 events to count. However, they stopped when they had reached 95 events, because the events stopped coming. I think that's good news -- both types of Maintenance seemed to work well.

In the end, though, they found that longer isn't necessarily better -- there was no real difference in Event Free Survival between the two groups -- neither approach seemed better than the other. There was also no difference in Overall Survival between the two groups, though the researchers want to continue looking at data for a longer time to see if that remains true.

However, the long-term group had a Progression-Free Survival that was much longer than the short-term group. (They kind of down-play this, though it seems significant to me. It's probably because their primary measure was EFS, and because the OS was the same, so it doesn't really matter on its own.)

The researchers point out several important things in their conclusion:

First, if there is no difference in EFS or OS between the two, then short-term seems the better option. It will be less expensive and cause less toxicity.

Second, there were more patients with "adverse events" in the long-term arm than the short-term. These include things like infections, which makes sense, since Rituxan kills off the B cells that fight infections.

Finally, they point out some of the limitations of their study, including their not measuring quality of life. It is possible that, for lots of reasons, long-term Maintenance could result in lower quality of life.

So in the end, the results are mixed. If anything, the study seems to back up the idea that Rituxan Maintenance can be a good thing (though they weren't trying to prove that it is better than waiting until Rituxan is needed before giving it), and the idea that short-term Maintenance is just as good as long-term, and maybe better, if you consider the cost.

Sorry, folks -- no Big Answers here. But I still feel OK knowing that even a small piece of the puzzle is being put into place.


Anonymous said...

Hi Bob: as Im busy updating myself with your posts, let me greet you and your family a belated Merry Christmas and a Happy New Year! my husband remains on W and W and is asymptomatic, last ct scan in May was very positive, everything remains stable, here's to good health and happiness! take care and thank you for the God-sent blog! - Jeanne

William May said...

Thanks Bob - again your blog is right on for my wife who was diagnosed with fNHL in 2011. She progressed within months of R-CHOP and BR. She has been on Idelalisib/rituximab for 14 months, fNHL is stable, and she feels great! She takes Idelalisib 150 mg twice a day, and took rituximab weekly for 4 weeks, then is taking rituximab every 8 weeks thereafter. So I think the Idelalisib/rituximab combo is very effective, at least for her. Another useful study would be to compare fNHL people who take Idelalisib/ rituximab and quit rituximab after the study protocol (weekly for 4 weeks then every 8 weeks for 4 cycles) vice those who continue rituximab every 8 weeks until progression.

Marcela said...

Hi Bob , I'm Marcela Canary Islands , but good news to start the year . Thanks to your blog I can be informed of the latest advances and treatments, I am lucky to find you. Here in the Canary Islands the new year we received on the beach with plenty of sun and with renewed hope to move on this and many more years. Health is there right around the corner insurance . Happy New Year to you and your family Bob!!! .
Excuse my translator, as you will see it has not changed with the new year