Saturday, March 15, 2014

ASH 2013: Dr. Jeff Sharman Discusses FCR versus BR in Front Line CLL

In this interview, Dr. Jeff Sharman gives us some understanding of the important trial data presented at ASH 2013 that compares FCR (fludarabine, cyclophosphamide, rituximab), the gold standard chemo-immunotherapy (CIT) to BR (bendamusine-rituximab) the new kid on the block and very popular with community oncologists.

In the excitement and promise of the new era of gentler and more effective oral medications for CLL, there is still a diminishing group of patients that for many reasons will continue to chose a chemo-immunotherapy (CIT) approach.

One possible reason is that for a few patients with excellent prognostic factors, a significant subset of those will reach MRD negativity and for that group FCR produces exceedingly durable remissions, starting to hint a possible cure. A half year of harsh but not the worst therapy, and you're done. Time to get on with your life without any daily pill reminding you that you have CLL.

Professor Hallek discusses this special group in my short interview from iwCLL last year.  I would not be completely dismissive of the value of CIT in those special circumstances.

Sadly insurance coverage and expense will be another reason that we will still see chemo. Older drugs are cheaper than newer drugs.

And even more sadly, patients' and physicians' unawareness of the rapidly changing therapeutic landscape will limit some of us CLLer's option to what our oncologist is most comfortable with it.

A few of us won't be able to tolerate the new oral therapies due to side effects, but as more options and new TKI's are approved I suspect that will be a vanishing small number. There are also the very few patients who have progressed on ibrutinib (the only oral TKI approved for CLL at this time and available by prescription) and an unfortunate group of us who both can not qualify for a trial or who have no access to the new meds because of where they live or their insurance and who need treatment NOW and can not wait for a different option.

That said, the FCR versus BR data welcomed as it is, is hardly the blockbuster news that it would have been a few years ago.

Ibrutinib and idelalisib and ABT-199 and obinutuzumab and others have rightly stolen the spotlight at ASH and elsewhere. Their time has come, and not a moment too soon.

Still CIT is not going to quietly fade away so fast so let's look at this important ASH abstract.

This link gives the data.

This link explains what is meant by the grade of adverse events and reminds us that a grade 3 adverse event is severe or disabling, a grade 4 is life threatening and a grade 5 adverse event is polite medical talk for a side effect that kills the patients. So when we see that on the FCR, we patients had a 90% of a Grade 3 or worst hematologic side effect compared to only two out of three in the BR arm.

The price of this higher that high toxicity and small but real risk of dying from FCR was an impressive 98% overall (ORR) response rate with nearly half of those being CR (complete responses). With BR the ORR is the same but the CR is 38%. MRD (minimal residual disease) negative data was not presented. Progression free survival was better for FCR in those under 65 years old, but not in the older group.

So very impressive results, but significant toxicity. This is an old and too common story with chemo: The more toxic the drug, the better it works. FCR is better in younger patients, but comes with more risks and misery.

New targeted and biological therapies break this paradigm and that is why when we have a choice, we should be putting the emerging therapies high on lists of options.

Remember too that this trial was for front line therapy in fit patients where access to the newer treatments in even more difficult.

Listen to Dr. Jeff Sharman and get his take on this important study. Dr. Sharman is a smart, very busy and compassionate guy who has done much to help the CLL and other blood cancer community and I am grateful for the time he gave for this interview at ASH 2013.

Dr. Sharman has an excellent blog himself where he covers much of the same and even more detail on the trial here.

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Anonymous Anonymous said...

For untreated in watch and wait stage with CLL... this would be such a difficult time to choose if therapy were needed asap. FCR appears to have the best proven outcomes with greater chance of MRD negativity or PFS. Many of us believe these new agents like ibrutinib may offer even better long term outcomes when used in combo therapy (e.g., ABT-199, ibrutinib and obinutuzumab combo?), or at least similar outcomes with much less toxicity, but we are a fair ways off from testing that thesis. Its certainly not proven. I suspect the best course for most untreated right now, would be going on one of the newer agents (ABT-199, ibrutinib, idelalisib) through a trial or in the case of ibrutinib, prescription, in hope that it buys enough time until the novel agent combo therapies are ready for trial.

But its frustrating... aside from the natural approval process required for single agents, combo therapy trials have issues with multiple drug companies needing to join forces to test their products together... and they don't like to play in each other's sandboxes like that. How can this be accelerated?! Does anybody doubt the possibility that a combo of ABT-199, ibrutinib, and obinutuzumab could very likely be a cure? If the execs of these drug companies had a spouse, child or grandparent with CLL who needed therapy soon, would they be so slow to pursue novel agent combo therapies? Its so close we can touch it, but we need to start testing it NOW!

March 17, 2014 at 12:05 PM  
Blogger Unknown said...

A couple of years ago, I had to have chemo. My CLL specialist had me do six monthly rounds of FR, not FCR. Is there a reason to go only with FR?

March 17, 2014 at 12:08 PM  

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