Controversies in Follicular NHL

Fascinating article in the Annals of Oncology -- a special issue devoted to work from the 11th Annual Conference on Malignant Lymphoma that took place in Switzerland about a month ago. The article is called "Controversies in Follicular Lymphomas," and discusses several controversial topics that are being debated by researchers and clinicians these days. (Follicular NHL treatment has been controversial for the last 10 years or so, from what I can tell. This is just a couple of the latest batch of controversies.)

The first controversy discussed has to do with first-line treatment: better to go with straight Rituxan, or Rituxan plus some kind of chemotherapy? (You know where I stand on this one, I'm sure.)

As for the first-line treatment controversy, the case for chemo is that chemo + Rituxan has significantly improved survival rates since Rituxan's introduction. Looking at data from studies involving chemo + R, it's clear that this treatment combo gives the best chance of a complete response. So the question becomes a matter of strategy: should we be encouraging complete responses for first-line treatments? Or is it better, given the long-term nature of fNHL, to emphasize management of the disease and be OK with partial responses or short-term complete responses?

On the other side, Rituxan by itself will not result in a cure, and in fact no treatment will (since we don't have anything that seems to be curative for most patients). But Rituxan alone will result in prolonged survival and a better quality of life (given the minimal side effects, compared to chemo). And given that a whole bunch of different chemotherapies seem to work, but none do as well without Rituxan, it seems that getting Rituxan on top of chemo is more important than getting chemo on top of Rituxan. Delaying chemo as long as possible cuts down or postpones the possibility of long-term side effects that might come from chemotherapy, and this delaying of chemo, and just going with Rituxan, does not result in a lower survival.

You know where I stand on this, having had single agent Rituxan as my first-line therapy. Quality of life is definitely as issue: all things considered, I've been pretty healthy and able to live a "normal" life for the last three and a half years. I'm OK with my decision to delay chemo.

The other controversy described in the article has to do with Rituxan maintenance, the practice of giving Rituxan at regular intervals (maybe every six months) for a couple of years after chemo. The first take on this controversy looks at Rituxan versus RadioImmunoTherapy (RIT) as a consolidation treatment (taken soon after chemo is finished). According to the article, both Rituxan maintenance and RIT (specifically Zevalin) have been shown to increase progression-free survival dramatically: over three years, compared to chemo without either follow-up. And for patients who took Zevalin and achieved a complete response, the PFS is about 5 extra years. The author leaves it up to the reader to do the math: multiple inusions of Rituxan versus a single infusion of Zevalin for the same post-chemo results.

I've long been an advocate for Zevalin (and the other RIT, Bexxar). The numbers are just too good to discount its use.

The other R-maintenance discussion in the article involves backround information: basically, studies continue to show that Rituxan taken after chemo does a great job of improving PFS. It seems to me that R-maintenance really isn't a controversy anymore. The NHL community seems to recognize its effectiveness, and it's becoming pretty standard practice.

It's nice to keep up on these controversies. Apart from the R-maintenance use, I don'ty see the other controversies going away any time soon. We're still nowhere close to agreement on a standard first-line treatment, and with the competing philosophies (manage the disease vs. wipe out the disease for as long as possible) guiding treatment decisions, I'm not sure an agreement is going to come anytime soon. As for RIT as consolidatoion, we have a log way to go there, too.

But the important thing is, those options are out there for people who need them, and are willing to educate themselves (and sometimes their doctors) about them. Better to have many choices than none at all.