Hematologic Oncology Update, Issue 3, 2016 (Video Program) - Video 20Case discussion: A 36-year-old man is newly diagnosed with chronic-phase chronic myeloid leukemia
5:30 minutes.
TRANSCRIPTION:
DR TIBES: CML is a disease that it can occur at essentially any age. I’ve seen it in the late twenties, midthirties to seventies. And a recent case I saw was a 36-year-old young male. He was in perfect normal health, very athletic. And then he noticed for the last couple of months increasing fatigue and shortness of breath after playing soccer. And he was a soccer coach as well, and he was playing soccer himself. And he didn’t think too much about it, because he never had any medical issues or problems. Then he went to his primary care physician, and he was found to have a white count in the range of 58,000, with a left-shift myelocytes, metamyelocytes, was mildly anemic with a hemoglobin of 11.8, normal platelets. And of course he was immediately referred to hematology. And primary care physicians may not be that familiar with CML. So when I saw the patient or the outside labs for referral, I saw him the next day, because it rings a bell for CML. So when he came to see me, we sent FISH for the BCR-ABL translocation 9;22 from the peripheral blood, immediately scheduled a bone marrow biopsy for a day or 2 days later. We started the patient on hydroxyurea/allopurinol. His renal function was normal. And a few days later, we received the results that, indeed, this is a BCR-ABL translocation. The bone marrow biopsy was done. And I do a bone marrow biopsy on all my newly diagnosed CML patients, because I want to know the status, if it’s truly CML in chronic phase. So he didn’t have any blasts in the peripheral blood, just the left shift and no increased blasts in the bone marrow neither. And I do send conventional cytogenetics on all my patients, because it may make a difference if you have additional cytogenetic abnormalities in addition to the BCR-ABL or the 9;22 translocation. So fortunately, this gentleman did not have any additional karyotypic abnormalities. And then the question is, how do you treat him? DR LOVE: Could I ask how long ago this was? DR TIBES: This was 2 months, 2, 3 months. DR LOVE: Oh. Just a couple of months ago. Okay. So could you talk a little bit about what you would consider potential alternatives for him and how you thought it through? DR TIBES: Yes. So, I mean, he’s a young gentleman. He still wants to have a family. And so obviously, once we established the diagnosis of CML in chronic phase, that’s important. So we go down the route of treating him with a BCR-ABL-specific tyrosine kinase inhibitor. So we have imatinib as the first-generation and the first one approved. We have nilotinib, dasatinib as the second-generation ones. And we have bosutinib. We also have ponatinib for relapse in the second or in the third-line treatment setting. So for the up-front treatment for CML in chronic phase, one can use imatinib or one of the second generation, nilotinib or dasatinib. So I think all the options are valid and they’re all recommended by guidelines. DR LOVE: So I’m curious with this man the kind of discussion that you had with him. What were the things that he was asking? How involved was he in making the final decision? And what did you two decide to do? DR TIBES: Yes. So I think first of all, I explained the disease to him. I explained that, at this stage, the recommended therapy is a BCR-ABL TKI. And we’re not proceeding to transplant unless he was in an accelerated phase or in blastic phase, obviously. So then I discussed the data with him fairly openly, that we do see higher molecular remission rates and faster with the second-generation TKIs, so nilotinib and dasatinib, but imatinib somewhat catches up later in the time course. I’m of the opinion that the earlier and the harder we hit the disease or the cancer, the better it is, because most data has shown this for most diseases. So you have to hit early and hard. So I usually start with the second-generation TKIs, unless there are contraindications, side effects or approval concerns. But again, I discussed the options of treatment, a second-generation TKI versus imatinib. And we opted to start him on nilotinib and with the prospect that at some point he may also enroll in a clinical trial after a couple of years of a deep molecular remission, an MMR, an MMR 4.5. And then he may have the option to go on a trial if there’s still a trial available at that point and then discontinue on a trial. I do know about trials that try to add interferon at some point or interferon after discontinuation to try to maintain the response. Because interferon has been used prior to the BCR-ABL TKIs and was an effective therapy, and interferon has an immune modulatory function. So in the initial trials, patients that did receive interferon actually may have had a longer treatment-free remission interval. That’s a new term that’s been formulated recently. So, essentially, how long can you keep a patient off a TKI in remission? |