Monday, January 9, 2023

25 Years of Rituxan

One of the ways I find out about what's happening in the world of Follicular Lymphoma is by Google Alert. I ask Google to let me know any time it finds something new on the web that mentions FL. So pretty much every day I get an email with some links. They can be anything from an article in a medical journal to a video on a web page for oncologists to a story in a local newspaper about a fundraiser for someone who was recently diagnosed. It gives me a pretty good sense of what's going on with FL.

So I was very intrigued by a notice I got a few days ago about an article in the Journal of Clinical Oncology called "Rituximab Chimeric Anti-CD20 Monoclonal Antibody Therapy for Relapsed Indolent Lymphoma: Half of Patients Respond to a Four-Dose Treatment Program." 

I was also kind of thrown off. I hadn't heard about any real new research in the use of Rituxan (its generic name is rituximab, and it's known in some parts of the world as Mabthera). I think it was the word "chimeric" that really caught my eye. "Chimieric" is the "C" in "CAR-T," so I thought maybe there was some new CAR-T -like version of Rituxan in clinical trials (but, again, I hadn't heard anything about it, and I usually would have). 

I did a little more digging, and it turns out that the article isn't new at all. In fact, it was published 25 years ago, and it's part of the JOC's "Flashback" series, where they republish important articles from the past and then include a commentary about it.

The commentary comes from Dr. Jonathan Friedburg, the editor-in-chief of the journal. His commentary is called "Flashback Foreword: Chimeric Anti-CD20 Monoclonal Antibody Therapy," and it makes clear just how important Rituxan has been to those of us with Lymphoma. 

So, just to be clear here -- This article is the first report from a clinical trial for Rituxan, from 25 years ago. The results were good, though not eye-popping by today's standards. There were 161 patients with several indolent lymphomas in the trial, and 48% had a response. The median duration was just under 12 months. Most side effects happened after the first or second of four infusions, with fever and chills being most common. [That was me -- allergic reaction with chills during the first infusion.] Only 12% had a severe side effect.

But that 48% response, as the article says, was comparable to single-agent chemotherapy at the time. 

It was the beginning of a very important period in Lymphoma research. As Dr. Friedburg's commentary points out, one of the important outcomes of the study was to show that Rituxan was especially effective on Follicular Lymphoma. The study looks at "indolent lymphomas," as the title says. FL is one of several slow-growing lymphomas that were often studied together in clinical trials (and still are). This study showed that the response rate for FL was 60%, while patients with another slow-grower (SLL) had a 13% response rate. This led future research to focus on FL in particular.

It was later on, when Rituxan was added to chemotherapy, that its importance really became clear. Rituxan just made other treatments better. Both single-agent chemo and Rituxan had response rates of just under 50%. But R-CHOP, combining Rituxan with several chemo agents, had a response of almost 90%. Pretty amazing. It's safe to say that Rituxan is at least partly responsible for the median Overall Survival of FL patients jumping from 8-10 years in the 1990s to 18-20 years today.

What amazes me most about Rituxan (and this is confirmed in Dr. Friedburg's commentary) is that researchers still don't exactly how and why it works. They have some very good guesses, but they don't really know for sure. You can watch this video if you want to see how Rituxan operates. Very cool.

As you know if you've been reading for a while, I am a big fan of Rituxan. I had single-agent Rituxan almost 13 years ago, and it has done its job for me all of that time. In years past, when I wrote about Rituxan in this blog, I'd call it "my best friend Rituxan." It's been very good to me, and to a lot of other patients with Follicular Lymphoma.

So there's your history lesson for the day. If you're looking for an excuse to have a drink, pour one and make a toast to Rituxan. My best friend definitely deserves it.


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