Tuesday, January 20, 2015

Rituxan and Beyond

OncLive posted a piece yesterday called "Moving Beyond Targeted Therapy Stalwarts: Experts Weigh in on Four Tumor Types." The idea is that the first targeted therapies for some cancers have now been around for a while, and it would be interesting to see how far we've come, and where we might be going.

Of course, one of the "four tumor types" is Lymphoma, and the "targeted therapy stalwart" being discussed is Rituxan, which has now been with us for 18 years (having been approved by the FDA in 1997).

(I'm not going to quibble with the idea that Lymphoma is a single "tumor type."  We all know that there are as many as 60 different types of Lymphoma. The article doesn't say that exactly, but does discuss a bunch of different types of Lymphoma. Let's just move on.)

The expert doing the discussing is Dr. Andy Chen from the Oregon Health and Science University.

As I said, this doesn't focus exclusively on Follicular Lymphoma, but even the non-FL stuff is interesting, particularly because of some of the stuff I've been writing about here recently.

Some highlights for me:
The introduction of rituximab to the treatment of patients with non-Hodgkin lymphoma (NHL) in 1997 has doubled median survival to 10 years for individuals newly diagnosed with high-risk, low-grade follicular - See more at: http://www.onclive.com/publications/Oncology-live/2015/January-2015/Moving-Beyond-Targeted-Therapy-Stalwarts-Experts-Weigh-In-on-Four-Tumor-Types#sthash.wQeQoXtM.dpuf
Knight Cancer Institute at Oregon Health & Science University (OHSU) in Portland - See more at: http://www.onclive.com/publications/Oncology-live/2015/January-2015/Moving-Beyond-Targeted-Therapy-Stalwarts-Experts-Weigh-In-on-Four-Tumor-Types#sthash.wQeQoXtM.dpuf
Moving Beyond Targeted Therapy Stalwarts: Experts Weigh In on Four Tumor Types - See more at: http://www.onclive.com/publications/Oncology-live/2015/January-2015/Moving-Beyond-Targeted-Therapy-Stalwarts-Experts-Weigh-In-on-Four-Tumor-Types#sthash.wQeQoXtM.dpuf
Moving Beyond Targeted Therapy Stalwarts: Experts Weigh In on Four Tumor Types - See more at: http://www.onclive.com/publications/Oncology-live/2015/January-2015/Moving-Beyond-Targeted-Therapy-Stalwarts-Experts-Weigh-In-on-Four-Tumor-Types#sthash.wQeQoXtM.dpuf
Moving Beyond Targeted Therapy Stalwarts: Experts Weigh In on Four Tumor Types - See more at: http://www.onclive.com/publications/Oncology-live/2015/January-2015/Moving-Beyond-Targeted-Therapy-Stalwarts-Experts-Weigh-In-on-Four-Tumor-Types#sthash.wQeQoXtM.dpuf
  • The article says, "The introduction of rituximab to the treatment of patients with non-Hodgkin lymphoma (NHL) in 1997 has doubled median survival to 10 years for individuals newly diagnosed with high-risk, low-grade follicular lymphoma." I think this is important to point out, because I read it three times before I really understood it. My first reaction was, "I think those numbers are low. Should it be "from 10 years to 20 years"? But then I read it slowly, and saw that the number was for "newly diagnosed with high-risk, low grade" FL. I think that's significant. We're not all considered "high risk," and that is measured by FLIPI or FLIPI2 scores. (See here for an explanation.) That's a particular sub-set of patients that has (as the name would suggest) a tougher form of Follicular Lymphoma than others. I don't know where that statistic (Rituxan doubles survival from 5 to 10 years) comes from, but it makes sense if we think in terms of high versus low risk. 
  • "In 2012, German researchers demonstrated that pairing bendamustine (Treanda) with rituximab significantly improved progression-free survival (PFS) over R-CHOP (69.5 months vs 31.2 months, respectively) as first-line therapy among patients with indolent NHL subtypes, including follicular lymphoma." Great news. However, as Dr. Chen points out, there is still the lack of an Overall Survival benefit to deal with (and that it's hard to measure because Overall Survival can go on for so long with Follicular Lymphoma patients). Not that anyone should be  complaining about increased PFS... 
  • And then there's the possibility of finding a monoclonal antibody to replace Rituxan. (18 years is a long time to be King of the MAB Hill.) One possibility is  obinutuzumab (Gazvya), which also targets CD20, like Rituxan. However, is was created using a process (called glycoengineering) that should make it more effective than Rituxan. It is already approved by the FDA for Chronic Lymphocytic Leukemia, and it is in a phase III trial comparing it to Rituxan in indolent lymphomas. We anxiously wait the results of that one.
  • A number of pathway targets have been approved (as we know), including Idelalisib/Zydelig. I found it interesting that these newer treatments have been more successful for indolent lymphomas like FL than for more aggressive lymphomas. I'm not sure why that's the case, but I find it interesting. Honestly, I don't pay a lot of attention to issues surrounding aggressive lymphomas, unless they are related to transformation. The article seems to suggest that treatments for aggressive lymphomas are not moving along as quickly as those for indolent lymphomas. I hope they make some progress for our brothers and sisters on the aggressive lymphoma side of things.
So, overall, there is some good stuff in the article. It's nice to see treatments talked about in comparison to Rituxan, which has been such a big help to us for so long.

6 comments:

Anonymous said...

I didn't think the FLIPI Score was still used as a basis for predicting overall survival. Do you know if this is true or not? Thanks!

Lymphomaniac said...

FLIPI is definitely NOT used to predict Overall Survival -- at least not directly. It's used in two ways, usually. The first is to group patients in clinical trials, so they are all at roughly the same place with their disease. (I think that's where the "high risk" categorization came from in this article.) The other way FLIP is used is by some doctors, who might base treatment decisions with FLIP as a guide. Low FLIP score = low risk = watch and wait. High FLIPI = high risk = CHOP. (That's just an example, of course. Individual doctors will make their own decisions.)
But it's not used to predict Overall Survival. Just too make factors that go into OS for ANY model to predict, especially since OS measures all survival, not just events related to cancer.

Karl Schwartz said...

re Dr. Chen writes: "The introduction of rituximab to the treatment of patients with non-Hodgkin lymphoma (NHL) in 1997 has doubled median survival to 10 years for individuals newly diagnosed with high-risk, low-grade follicular lymphoma."

Hi Bob, Thanks as always for your thoughtful pieces. High risk FL is now thought to be associated strongly with treatment resistance (early relapse) ... based largely on the long or short duration of response to Rituxan-based treatment at 12 months. So for this reason I'm skeptical that the doubling of survival benefit for the addition of Rituxan is specific to high risk FL. More likely, it's the other way round.

See ASH report 1664 Event-Free Survival at 12 Months (EFS12) from Diagnosis Is a Robust Endpoint for Disease-Related Survival in Patients with Follicular Lymphoma in the Immunochemotherapy Era

Karl
PAL www.lymphomation.org

Rodrigo Carvalho said...

Dear Karl Schwartz.
What a great new!!
Goodbye FLIPI.
Rodrigo

Anonymous said...

Hi not related to FL but stay safe during the storm. My thoughts are with you
Mel from NZ

Lymphomaniac said...

Thanks, Mel. We're doing OK so far -- not as much wind and snow as they were predicting. Looks like things are a little rougher to our east.