EJM: New Paradigms for FL

Let's keep this theme going. The European Medical Journal published an edition that looked back at the European Hematology Association conference from last June.  In all of my reading about Follicular Lymphoma, it seems like the kinds of research that gets done in the U.S. is the same as in other parts of the world, more or less, but I enjoy getting a different perspective on things.

One section of the journal is called "Shifting Treatment Paradigms in Non-Hodgkin Lymphomas," and in that section is a piece called "Follicular Lymphoma: Strategies in the Era of New Targeted Therapies." [The link should take you right to the article on FL, but if it doesn't, scroll to page 36.]

The FL article is written by Professor Dolores Caballero from University Hospital Salamanca in Spain. She gives a sense of the current state of treatment and its results. In a nutshell:

The median Overall Survival for FL is about 15 years. [Remember "median" means half of patients will survive less than that, and half will survive more. Also remember that most FL patients are diagnosed in their 60's; the media OS for younger patients is much longer than 15 years.] Common options are watching and waiting, straight Rituxan, and immunochemotherapy (usually Rituxan + CHOP, CVP, or Bendamustine.)  Patients with no symptoms often get W & W or Rituxan; patients with a higher tumor burden often get R + chemo. Some benefit from Rituxan Maintenance. Some more aggressive approaches seem to improve Progression Free Survival (how long it takes until the disease starts to get worse), but don't improve Overall Survival.

That about sums it up, right?

Prof. Caballero continues: While something like R-CHOP might increase PFS, it also comes with side effects that affect Quality of Life. Traditional chemotherapy attacks healthy cells as well as cancer cells. What we need (and what we have) are treatments that focus on the cancer cells and leave everything else alone. This should result in fewer side effects. And since FL is a heterogeneous disease -- it's a little bit different for everyone -- it would be good to have a bunch of options.

And that's what we have. Prof. Caballero gives a brief discussion of some of the targeted options available, and how well they have performed in trials. These include Obinutuzumab (combined with chemo, it had a higher 3 year PFS  than Rituxan + chemo), Idelalisib (a PI3K inhibitor, which seems to work best with patients who are high risk and have had several prior treatments), Ibrutinib (a BTK inhibitor with high response rates), and Lenalidomide.

Lenalidomide gets the most discussion here (it's not a long article, but it gets about 4 paragraphs). An immunomodulatory agent, it has been combined with Rituxan to create "R-squared" (Lenalidomide also goes by the name Revlimid). It's a combination that has had lymphoma specialists very excited for a few years.

Dr. Caballero finishes by pointing out that next generation treatments will combine biologic and targeted agents, in ways that are based on individual patient needs. But we need to learn more about biomarkers -- those clues that help predict which patients will respond to which treatments even before they try them.

So, looking at the trends here, and comparing what a European expert is excited about to what American experts seem excited about, I'd say Lenalidomide is near the top of everyone's list. More targeted treatments like inhibitors are also up there. And there's plenty of buzz about CAR-T.

The big lesson I'm taking away is that we have a lot of options, and more on the way. And if you think about some of the combinations that are being tested, that's even more still.

The future looks bright, on both sides of the world.