Published on March 16, 2018
Could chronic lymphocytic leukemia (CLL) patients be treated successfully with novel agents after using a fludarabine, cyclophosphamide and rituximab (FCR) regimen? What is the role of FCR in today’s treatment landscape? CLL experts, Dr. Jennifer Brown and Dr. William Wierda, joined us at the American Society of Hematology (ASH) 2017 annual meeting to discuss the effectiveness of novel agents post-FCR. Dr. Wierda also shares what the approach is for new therapies in development. Watch now to find out more.
This program is a Patient Empowerment Network program produced by Patient Power. We thank AbbVie, Inc. and Genentech for their support.
Transcript | Post-FCR: Will Novel Treatments Still Work for My CLL?
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Jennifer, there are many people who are watching who have had FCR. I had it in 2000 and 2001, and many of us have gotten a long remission, but we come out of remission. So, first of all, are we damaged in any way because we had FCR where these novel agents or these combinations you're talking about are less likely to work, because we were previously treated with an FCR or a BR?
No, really not. I mean, when we started testing these drugs it was inpatients who had many, many rounds of prior therapy, and they worked phenomenally well, and as we moved them earlier they continued to work phenomenally well. In fact, in some of the randomized trial data with ibrutinib (Imbruvica) there is evidence that at least at two years getting ibrutinib second line was associated with about the same sustaining of response as getting it frontline. And so I think that there's not a concern—the novel agents continue to work extremely well in most patients over time.
Okay. Okay. So, Bill, you were talking about these studies about ibrutinib and venetoclax (Venetoclax), and the goal, say, can we stop it at some point, and there's another leukemia, CML, where people were taking a medicine and there have been trials, cessation trials to see if you could stop. One wonders if you have a remission and you get to this MRD negative point but you fall out of it at some point, the cancer show its head again, can the medicines work for you again, or have you kind of exhausted that option?
So that's a great question. That's a question that we have limited data on so far. So for example there was a trial that was done with venetoclax plus rituximab in which many patients went into a deep remission and were MRD negative. A few patients went off treatment and had been followed, and subsequently their disease did come back, and they reinitiated treatment.
Now, the numbers are low, but those patients responded again to treatment who they restarted on treatment. So, so far it looks like the patients can be retreated without expecting them to be resistant, and we need to collect more information on just that question.
Or can you retreat with venetoclax after you have had a good, deep remission and patient's disease has come back. I think yes. With chemotherapy it was the same question or chemoimmunotherapy. We would give patients six cycles of FCR. They'd go in remission. There was a variable length of remission between patients. Generally speaking the longer the duration of remission the more likely patients would be to respond when you gave them the same treatment again later. It may be the same pattern we see with the small molecule inhibitors. We don't know yet though.
All right. I have one question for you, staying on you, Bill for a second. So I had FCR at MD Anderson years ago, and then the trials went on around the world, and many of us have had it. So the F and the C, chemo drugs, right? And I know the worry has been does it lead to a second cancer or the toxicities etc. So as you're talking about novel agents and monoclonal antibodies, kind of nonchemo kind of drugs, is the F and the C, or the B, bendamustine (Treanda), are those passé now, do you think?
Well, right now we're not willing to dispose of those drugs for certain groups of patients. With the FCR experience, and we have years of FCR experience and hundreds of patients literally treated at MD Anderson with the FCR regimen, we have an idea about who does best with that regimen. That is, what is the group of patients that is most likely to go in remission and to have the longest remission and perhaps cured with that regimen, and those are patients who have a mutated immunoglobulin, heavy chain variable gene. So we think that that regimen particularly is important for that sub group of patients, and that data has also been confirmed by other groups like the German CLL Study Group.
So our new regimens right now are modifications of FCR, intended to give less chemotherapy because we are worried about that risk for second malignancies and selection of—for 17p and things that happen when patients get chemotherapy that might not happen with the small molecule inhibitors. We don't know as—we don't have as much data on that, but—so we're trying to give and develop regimens that have less chemotherapy that will achieve the same end point. And we haven't yet given up on chemotherapy, but particularly for a group who benefits most and potentially are cured with it.