Advances in treatments for haematologic malignancies from the Sarah Cannon Research Institute presented at ASH 2012 (1/5)
Dr Ian Flinn – Sarah Cannon Research Institute, Nashville, USA
Tell us about your first presentation at ASH 2012: fludarabine, rituximab and lenalidomide in previously untreated patients with CLL.
This is a trial combining fludarabine, rituximab and lenalidomide for patients who have previously untreated chronic lymphocytic leukaemia. The concept here was that we knew that FCR is a great regimen, the standard of care for many patients with previously untreated CLL. The issue is that there are concerns about the addition of cyclophosphamide to the fludarabine backbone for increased myelosuppression, perhaps myelodysplasia and there is a large US inter-group trial that showed that patients who received the fludarabine and cyclophosphamide had an increased incidence of myelodysplasia. So we were hoping to find a different regimen, perhaps as effective as FCR, but perhaps without some of these long-term effects and some immediate effects.
So lenalidomide, we know, is a very effective drug in multiple myeloma, it’s a very effective drug in myelodysplasia itself and it’s making its way in CLL as well. So we wanted to combine that, replace the cyclophosphamide with lenalidomide in that regimen. So this is the results of that trial and it shows that it is a highly active regimen in a fairly poor risk group of patients. One of the issues was how to combine it because it does also have some problems with myelosuppression so what we tried and learned was that it’s better to give it not concurrently but in a sequential but cyclic approach. So we’re giving fludarabine rituximab for three days and then patients have four days off and then on the eighth day we come back in with lenalidomide. It’s given step fashion so in the first cycle patients get a smaller dose and in subsequent cycles they get a slightly higher dose. I think that this is an interesting approach; what we really need to do is find out in the long term whether this improves progression free survival. So far it looks pretty encouraging.
Explain more about the adverse effects?
There was a unique side effect in that there was significant increased numbers of rashes. I’m not talking about just the minor rash, these are pretty significant rashes and we’re really not sure why that happens. We give a lot of people lenalidomide, we give it to patients with multiple myeloma, a lot of patients with MDS and all the doctors are used to that kind of rash. This was worse and this was significant and so I’m not sure what… these are immune modulating agents and whether there’s something about the milieu after chemotherapy that augmented this rash, I’m not sure. But it is a reasonable regimen given in this dose and in this schedule we think it’s well tolerated.