The Best First Line Treatment for Follicular Lymphoma?

If you have paid any attention to Follicular Lymphoma treatments, you know that there is very little agreement among experts on which treatment is best to try first, which is best after that, etc. Watch and wait? Straight Rituxan? CHOP or Bendamustine? Newer treatments are making those questions even harder to answer.

Researchers in Italy have made the most recent attempt at an answer. Their article "The Use of Anthracycline at First-line Compared to Alkylating Agents or Nucleoside Analogs Improves the Outcome of Salvage Treatments After Relapse in Follicular Lymphoma The REFOLL Study by the Fondazione Italiana Linfomi" appears in the January 2015 issue of the American Journal of Hematology.

(I can't get access to the full article; I'm working from the abstract, which is linked above.)

Basically, they want to know if using certain types of treatments are more successful than others when used as a first treatment for FL, because they improve the treatment that comes right after that (salvage treatment). They looked at the records of over 500 patients to find an answer.


They compared three types of treatments: alkylating agents, which mess with DNA (these include Bendamustine and Cyclophosphamide, the "C" in CHOP and CVP); anthracycline (also known as Doxorubicin or Hydroxydaunomycin -- the "H"in CHOP); and nucleoside analogs, which mimic pieces of DNA and get in the way of cancer cells reproducing.

I don't have the names of specific treatments used in the study, but my guess is that they used CVP for the alkylating agent, CHOP for the anthracycline, and Fludarabine for the nucleoside analog. Just a guess.

(By the way, if you want t know more about these different types of chemotherapy agents and combos, Lymphomation.org does a nice job of laying them all out and making sense of the alphabet soup that chemo treatments often come to us as.)

What they found was that anthracycline (CHOP) did the best job, with the longest time-to-next-treatment. It didn't matter if the CHOP included Rituxan or not, and it didn't matter what the salvage treatment was (Rituxan Maintenance and Auto Stem Cell Transplants were among the possibilities).

Their conclusion: "This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line."

I've said this before, but it's worth saying again: this is great to know, but I wonder how much longer it's going to matter.  More and more lymphoma experts are telling us that traditional chemotherapy is on its way out. This study, which looked to the past for its data, is telling us something that just might not even be an issue in a few years. So I'm not sure we should be in a hurry to ask for CHOP when the time comes for treatment. I'm not certain, as I said, but I don't even think Bendamustine was used in this study. That would have to skew the results some, given what we know about B-R compared to CHOP.

The study's assumption is important: it assumes that the best first treatment is the one that takes the longest to get to a next treatment. And I think that assumption is on its way out, too. More and more newer treatments are focused on assuming that Follicular Lymphoma will be a chronic disease, one that we manage, not that we push off. In other words, we'll take a daily pill for years, rather than a few months of chemo and then wait it out.

On top of all of this, what we know about Transformed FL seems to indicate that CHOP, followed by an Auto SCT, might be something to hold off on, best used for Transformation, rather than as a first treatment for an indolent disease. That's debatable, of course, but something to be considered before declaring CHOP/anthracycline as the best first treatment.

If nothing else, this study highlights that we're at a crossroads for Follicular Lymphoma treatment. We'll see new ways of treating, and they'll come with whole new sets of assumptions about how and when to treat.

It's going to be an interesting few years for all of us....