Steven P. Treon, MD, PhD:In this particular case, the patient then relapses 2 years later. Now we’re dealing with a patient who has a rising IgM [immunoglobulin M] level. His lymph nodes are no longer bulky. And so, this case has actually changed. When the patient now comes back to us, we no longer are dealing with an oncologic emergency. Now we have other options that we can consider in the care of this patient. What we would not want to do is add in alkylating agents because we don’t want to potentiate any damage to his stem cells. So this is really where we have some time to think about what’s best for this patient and to manage him with other treatment options.
In the second-line setting, where this patient does not need emergent therapy, we would still be mindful of using a proteasome inhibitor, potentially. I think the fact that he still has adenopathy might sway me against that. Ordinarily, proteasome inhibitors are really good at cleaning out disease in the marrow but are not so good at dealing with extramedullary disease.
I would avoid using alkylating agents in this particular case. I would also avoid a nucleoside analogue because, again, if he’s young, we don’t want to put him at risk for secondary malignancies or myelodysplasia. This is a particular patient who I would actually get very excited about using ibrutinib in at this point in time. We know he has theMYD88mutation. We also know that he has theCXCR4mutation, but we’re no longer dealing with imminent disease control that would be required. One has to understand that if one has aCXCR4mutation, you have to set expectations. You know this is not somebody who’s going to respond overnight to a drug like ibrutinib. It may take a while. That’s why it’s important for clinicians to know about the mutation status of an individual. Then you can set expectations. You won’t panic after a couple of months if you are not seeing a major response, understanding that it may take time in somebody who has aCXCR4mutation.
The fact that the patient did well for 2 years would also suggest to me to use ibrutinib along with rituximab in this particular case. One could certainly use ibrutinib alone, but since the patient did have benefit with the 2 drugs togetherthe bendamustine and rituximab up front—I think it would be very reasonable to use both drugs together. We know from the iNNOVATE study that the patients who got ibrutinib and rituximab together showed improvement over rituximab alone. For somebody who has aCXCR4mutation, I think the combination would be reasonable.
Transcript edited for clarity.
A 42-Year-Old Male With Relapsed/Refractory Waldenström Macroglobulinemia