Breaking News: Six Idelalisib Combination Trials Halted

Published on

Topics include: Treatment

After serious adverse events were reported in patients, Gilead Sciences, Inc. has halted six clinical trials using idelalisib (Zydelig) in combination with other drugs.  The trials were investigating use of the drug in chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and indolent non-Hodgkin lymphomas (NHL). Leading expert Dr. Jeff Sharman joins Patient Power to explain what happened and what it could mean for patients.

View more programs featuring

Transcript

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.

Dr. Sharman:

Hello.  My name is Jeff Sharman.  I am the medical director of hematology research for the US Oncology Network. 

This last week we had some interesting developments with the molecule idelalisib, also known as Zydelig.  This is a medication used in patients with chronic lymphocytic leukemia and follicular lymphoma, which are the two areas where it's been approved by the FDA.  What specifically happened this week that was new was that a handful of clinical trials were stopped abruptly based upon new safety information.  

Now, these drugs have been used and again approved by the FDA on the basis of improvements in outcome, so how come these studies got closed?  Well, it's actually not the most straightforward explanation, and I'll do my best to unpack this.  In patients with relapsed chronic lymphocytic leukemia, generally we've seen three clinical trials where idelalisib led to improvements in outcome.  In at least two of those studies, there is even a survival benefit, which in CLL is a high bar to prove.  

In follicular lymphoma, when we look at those patients with heavily pretreated and refractory disease, we don't have comparative studies released just yet, but at least the single-arm studies show significant favorable impact with idelalisib.  So what changed?  Well, the studies that were terminated were all early-stage studies, generally speaking, previously untreated CLL or very lightly treated follicular lymphoma. 

So why would that be?  Well, it may depend when in the treatment course somebody gets idelalisib.  We know that the target of idelalisib, this molecule called PI3 kinase, is really important for immune regulation.  That immune regulation may have differential outcome early in the disease versus late in the disease.  So late in the disease when patients have had lots of prior chemotherapy it may not have as significant an impact as it does early in the disease. 

Now, at ASH 2015, we saw a presentation that showed frontline use of idelalisib in chronic lymphocytic leukemia was associated with a very high rate of immune consequences and dysfunction. And what the new data shows is that not only is there a high level immune dysfunction where you get high rates of liver function test abnormalities, pneumonitis and so forth, there is also probably an immunosuppressive effect.  

And what I mean by that is that we saw a higher rate of infectious complications for those patients treated early.  So we saw high rates of an unusual viral infection called CMV, cytomegalovirus, and we also saw this somewhat unusual lung infection called PCP. It also goes by the name of PJP, there are a handful of names for it—and this resulted in higher rates of adverse outcomes, serious adverse events, meaning hospitalizations, and even a few excess deaths.  

So as I stand back and look at this, we have a very discordant picture where it's very clear that late in the disease idelalisib is associated with very favorable impacts on patient well?being, and early in the disease it tends to be associated with more adverse events.  So I think it helps us to understand perhaps how to sequence the drugs. 

Now, for those patients who are currently on idelalisib, those patients in clinical trials where the clinical trials have closed, they're taking patients off the drug.  So I believe there are a total of six clinical trials. And if you're in a clinical trial with idelalisib, your study site should be able to tell you right away.  For those patients who are getting idelalisib as a prescription, there should be a discussion about risks and benefits.  

So if you're—early on in the development of the drug we were commonly trying to prevent PCP infections, and then I think once the drug got approved it sort of became less of an issue, but now it's an issue again.  So there are ways we can prevent PCP pneumonia, and you should talk with your doctor about that.  

And CMV viruses can cause a variety of unusual infections, sometimes intestinal infections, sometimes liver infections, lung, there are a variety of places that can involve this, and so there should be some monitoring for CMV.  

So those are the updates with idelalisib.  We again still know that it's an effective drug in a number of circumstances improving survival, improving outcome later on in the disease. But early in the disease there's some new safety concerns that would prevent us from are broad utilization of the medicine. 

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. 

Advertisement
Join Our Community Register for Events Read Our Latest Blog
Advertisement

Page last updated on March 29, 2016