Could Using Newer Treatments As a Frontline Approach Decrease Future Efficacy of FCR?

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Will using newer treatments, like ibrutinib (Imbruvica), as a frontline treatment decrease future efficacy of FCR if the patient becomes refractory? Dr. Jeff Sharman, Medical Director of Hematology Research with the US Oncology Network, shares his insights and the role of biomarkers, including IGHV and FISH.

Sponsored through an educational grant from the Patient Empowerment Network, which received support from AbbVie Inc. and Genentech Inc.

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

Andrew Schorr:

We're here with Dr. Jeff Sharman from US Oncology Network, a noted expert in CLL.  Dr. Sharman, here's a question we got in from one of our members.  They write, will using newer treatments like ibrutinib or Imbruvica as a frontline therapy for treatment?naive patients decrease the future efficacy of FCR if the patient becomes refractory to those novel agents? 

Dr. Sharman:

One of the challenging questions that the new agents are creating is what's the proper sequencing of these drugs, and what we don't know because the clinical trial data doesn't give us these answers is what's the right order to do them in.  The way that drugs get approved is not necessarily the same as the way we decide what order to use them in. And so if the question is does using ibrutinib (Imbruvica) up front diminish the activity of more traditional therapies down the road, the answer is simply we don't know.  We really don't know, and there's nothing that's likely to give us that answer very clearly. 

I think one of the paradigms has been that you always put your best foot forward first, and the degree to which we can—or, excuse me, the nature of the responses, the quality of the responses diminishes in subsequent lines of therapy for most drugs, and that's always been a paradigm that's been real.  And so that's at least true when you sequence different lines of chemotherapy, but what is simply not known is will that be true when we use a targeted agent first.  

I think perhaps underneath your question is a different question which is what's the—you know, how would we approach first?line chronic lymphocytic leukemia? And I think that this is an era where we can maybe drive answers that are more biomarker driven.  And so some people have reserved ibrutinib for those patients with higher risk features, some with lower risk features, and in my own practice I put a high priority on the IGHV mutation analysis. And for those patients who are IGHV mutated, they're oftentimes going to do very well with chemotherapy provided they're FISH is good too. 

On the other hand, if they're IGHV unmutated, frequently they're not going to do as well on chemotherapy, and that would be a patient where I likely would move towards a tyrosine kinase inhibitor first.  For those patients with be favorable IGHV, favorable FISH, they may derive a very substantial benefit from chemotherapy, and so that's where I'm still using chemotherapy within my own practice. 

Andrew Schorr:

Dr. Jeff Sharman from US Oncology Network, thanks for being with us and for taking questions from our CLL members. 

If you, a member of our CLL patient community, have a question, just send it in to CLL at patientpower.info.  I'm Andrew Schorr.  Remember, knowledge can be the best medicine of all.  

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

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Page last updated on December 23, 2016