Bendamustine: Good, But Not As Good as We Thought?

Lymphoma Rock Star Dr. Bruce Cheson of Georgetown has a video out today on Medscape News Today called "Is R-Benda a New Standard in Lymphoma?" (The link provides the 5 minute video of his commentary plus a written transcript of what he says.) Cheson reviews the article "Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial," published lats month in The Lancet. This is the results of the article that explains the clinical trial that established that Bendamustine + Rituxan is superior -- vastly superior -- to R-CHOP, both in effectiveness and toxicity. In other words, B + R works better and has fewer side effects. As Dr. Cheson asks in his title, Bendamustine has pretty much proven itself to be the standard for Follicular and other indolent lymphomas.

Dr. Cheson has some fascinating commentary, however, which raises some questions about the study, and thus about whether B + R is as effective as this research would suggest.

For example, Dr. Cheson takes issue with the way the effectiveness was measured. The measurement used was Progression-Free Survival -- how long it takes for the disease to be present again. One problem, says Dr. Cheson, was that patients were tested every 6 months, in a way that wasn't consistent, which throws off the measurement. They were also tested with CT scans, rather than PET scans. A CT scan will show growth in nodes, but not necessarily the presence of cancer. The PET is a much more sensitive instrument, and could possible detect cancer earlier (as would a more frequent scan). It's possible that the disease was actually present much sooner in some patients than was detected.

Another problem, says Dr. Cheson, was with the side effects listed. Clearly, B + R has much, much less toxicity than R-CHOP, as measured by something like hair loss (inevitable in CHOP, nonexistent in Bendamustine). But Dr. Cheson, who frequently prescribes B + R, reports lots of patients with "profound fatigue" (something I have also heard from friends in the support group), though this study downplays this side effect. 

So, maybe, in some small way, Bendamustine isn't quite as good as thought? 

Now, all that said, Dr. Cheson isn't planning on stopping his use of Bendamustine, because it certainly does work. And despite what he says, I don't plan to call Dr. R and tell him we need to talk about whether or not Bendamustine is the best choice for me. That's the one we're planning on when I need treatment next, and I'm still planning on it. Even if it's "only" as effective as R-CHOP, it would still do the same job with much less toxicity, and to me, that would be worth it.

But maybe the most fascinating thing in this video comes at the end, when he addresses the question in his title: Is Bendamustine the standard?

Here's how he ends the video, before signing off:

It is an interesting and important day because we finally have the opportunity to carefully evaluate the data that have been presented for many years. Take a peek at the paper. See how you assess the data as published and how it may affect your practice. It is an interesting time. I predict that this study and the Bright study will be irrelevant in a few years, with all the new kinase inhibitors and proapoptotic drugs that are out there. But at least for now, R-CHOP and R-bendamustine are a part of standard practice, and now we have the opportunity to see the data on the basis of which practice was changed. [I added the emphasis.]

Maybe it doesn't even matter? Maybe we'll all be on Ibrutinib or some other kinase inhibitor in a few years? That's a pretty awesome prediction from a Lymphoma Rock Star.

It really is an interesting time.