Rituxan and Transformation (Part 1)

I've seen two studies in the last couple of weeks that look at the role that Rituxan might play in preventing Transformation in Follicular Lymphoma. They both present some possible good news, though, like most research on FL, they also show how complicated all of this is for us.

Transformation, of course, is one of the biggest fears of FL patients. When the disease transforms, that nice, slow-growing disease turns into an aggressive, faster-growing disease. Survival rates for transformed FL are lower than for "regular" FL. 

The first of the two recent studies was published a couple of weeks ago in The Lancet Haematology, called "Rituximab and the Risk of Transformation of Follicular Lymphoma: A Retrospective Pooled Analysis."

A retrospective pooled analysis means that the researchers didn't start a new study themselves. Instead, they looked back at a bunch studies that other people did and examined how many patients transformed and what kinds of treatments they had.

They looked at 10,001 patients' records (a pretty big group). The patients had been diagnosed between 1997 (when Rituxan was first given to FL patients) and 2013. Of that 10,001 patients, 8,116 were able to be included in the study, and 509 of them transformed.

The rate of transformation over 10 years was 5.2% for patients who received Rituxan, and 8.7% for those who did not.

For those who received Rituxan, it broke down further -- a rate of 5.9% for patients who receievd only Rituxan for their first treatment, and 3.6% who had Rituxan as part of their first treatment and also as part of Maintenance.

Of those 509 patients who transformed, 287 died during the study, with a 10 year survival after transformation of 32% (that number was the same whether the patient had Maintenance or not).

Overall, those numbers are good. As the researchers say, "These findings support the need to inform patients using rituximab nowadays that the risk of transformation is lower than it was before the introduction of rituxumab."

Interestingly, these numbers are even better than when they were presented at a conference last year.

Hard to argue with the researchers' conclusion. The numbers for transformation rates have always been very high -- I've seen them as high as 50%. In other words, whether we transform is a coin flip.

But that's old news. More and more studies of transformation give lower numbers. The ones I have seen in the last couple of years mostly have been in the teens. 

I also find it interesting that the conclusion says that patients should be told that the risk of transformation is lower now than it has been since before the introduction of Rituxan. It seems like that is meant to be an encouragement to use Rituxan. But that's kind of strange -- almost every treatment these days includes Rituxan. It seems like a capital-t Truth that Rituxan is part of everyone's plan. We are far more likely to get Immunochemotherapy (R + something) than just chemotherapy.

But as I thought about it more, I realized that lots of newer treatments are being tested as single-agents, not combined with other things. Of course, they are also tested (and often found to be more effective) with other agents as combos (R-squared is more effective than just Revlimid).

And that also made me think about other issues, like whether Rituxan biosimilars (cheaper, "generic" versions of Rituxan) would be as effective, or if Obinutuzumab or other monoclonal antibodies would also have the same effect on transformation.

So much to think about.

For now, though, I will take the good news that risk of transformation does seem to be getting lower. Whether or how those other complexities  play out will be something to watch for in the years to come. (This study looked back at patients from 20 years ago, so I wouldn't expect anything about single agents or others MABs any time soon.....)

The other recent study on transformation looked at Rituxan Maintenance and its effects. More on that next time.