DR TIBES: A 54-year-old female who had induction and spring consolidation. She was allowed to transplant. There was some donor search issues and some insurance approval. Then she unfortunately relapsed sometime in July, had salvage with another regimen, MEK chemotherapy salvage, had a second remission, which was very short lived.

And yesterday afternoon she came to the emergency room with a white count of close to 100,000, 98% blasts, platelets 8,000 and fulminate relapse of her AML, so her second relapse, so to speak, within only 6 months.

DR LOVE: So this woman coming in just last night, I’m sure this is really on your mind right now. What are you thinking?

DR TIBES: What’s on my mind is what other therapies can we offer this woman, because in an acute myeloid leukemia — and she had actually diploid cytogenetics. She was diagnosed at the outset first and then came to us for consolidation after initial induction. And we knew that she was an NPM1-positive, but there was no reported FLT3 status from the outset hospital. And since she was in remission initially, when she came it was difficult to repeat that. You can add FLT3 testing on the outset slides and blocks, but it was difficult to obtain those.

So essentially when she came in yesterday, of course we stabilized her. We hydrated her. We gave allopurinol. And then we initiated plasmapheresis — leukapheresis last night still to take — because she had early signs of leukostasis. We don’t do leukapheresis often, but she was with 98% blasts and a white count of 100,000, so we initiated leukapheresis, initiated hydroxyurea, 1 gram q8 hours.

And I admitted her to the inpatient service as well as ordering a bone marrow biopsy for today as well as send all her flow cytometry from the peripheral blood. I mean, we knew there was blasts. It was a relapsed AML, but we still wanted to confirm a myeloid phenotype. And the other thing is, we are also sending FLT3 mutation testing. And why are we sending this? Because it does make a difference. FLT3 is one of the most commonly mutated genes in AML in general, particularly in diploid cytogenetics, or normal karyotype you find it in up to 25% to 30% of the patients either with NPM1 positivity or without. So often you do find NPM1 and FLT3 together. And we didn’t have the original specimen. As I said, she was diagnosed at an outside facility.

And often patients with an FLT3-positive AML, they often have leukocytosis and a very high white blood cell count. So when I see a patient — and what I teach the fellows on the service — and then we have a leukemia with a white count of 150,000, it immediately rings a bell. Could this be an FLT3-positive leukemia? Why is this important? Because particularly in a patient where we’re running out of salvage options, 2 relapses within 6 months, she’s essentially refractory to chemotherapy.

And there’s several FLT3 inhibitors currently in clinical trials, and there’s first- and second-generation FLT3 inhibitors. And they have shown overall, I would say, rather good-to-encouraging response rates, depending on which FLT3 inhibitor. If you have a response rate defined as a CR, which is a complete remission, or a CRI, incomplete count recovery, which is still useful, so essentially receiving a remission in 40% to 50% of the patients. And that’s across the different FLT3 inhibitors.

None of those FLT3 inhibitors are approved yet for FDA usage. However, there are large clinical trials ongoing. And I do think patients with FLT3 mutations, particularly at relapse but also the up-front setting, should be offered an FLT3 inhibitor on a clinical trial if one is available.

DR LOVE: So if I could ask you a few questions about what you just said, first getting back to this patient, how exactly is the FLT3 assay done, the one that you just sent on her? And how long is it going to take to get back?

DR TIBES: So the initial diagnosis, we send it from the bone marrow biopsy often. However, you can also send — if you have a significant peripheral blast percentage, you can send it also from the peripheral blood. The turnaround time varies if you’re a hospital, if your center offers it or if it’s a send-out test. Some centers can turn it around within 1 or 2 days, but it shouldn’t take more than 2 to 5 days, so a few days. And it’s very important, vital information. So it’s essentially an easy, reliable test and it helps in the management of patients.

DR LOVE: So if her FLT3 test, as you maybe are somewhat suspecting, comes back positive — you said that none of the FLT3 inhibitors are approved. But, I mean, sorafenib is approved. So first of all, would you consider sorafenib? And second of all, what are the agents that you would like to see — what you would like to see her get on, if you could?

DR TIBES: Yes.

DR LOVE: Obviously there’s gilteritinib, there’s midostaurin.

DR TIBES: Yes. Very good question. Sorafenib is approved for other indications, for solid tumors, HCC or renal cell carcinoma. And actually I have used in patients with FLT3-positive AML off label. And there is data from clinical trials from various institutions in using sorafenib in addition to standard chemotherapy. There were studies from the MD Anderson. There were studies from the German Leukemia Group.

And the response rates in FLT3-positive patients where sorafenib is added approaches 90%, 95% to close to 100%, the initial CR rates. The overall survival and the response rates were not that different. So it does make a difference, adding sorafenib to chemotherapy, achieving remissions. There may be a benefit if you continue sorafenib, because the initial trials did not continue it for longer term. So continuing the FLT3 inhibitor after the induction/consolidation, I think it’s 1 approach, also how you sequence it.

DR LOVE: So a maintenance kind of strategy.

DR TIBES: Correct, maintenance. So adding it to induction, and then a maintenance strategy. Sorafenib also has been given — there are Phase II study data with azacitidine, for example. So I have used it several times in older patients that are not induction candidates, because of age, because of comorbidities or preferences of the patients. So I have given sorafenib with azacitidine off label and have seen good responses. And there’s Phase II data, Blood paper and some other papers published. So in the community, it’s sometimes important to have this information available for insurance approval. So there’s data out there. That’s just the message I want to send out to my colleagues.

Non-Hodgkin lymphoma (NHL), Hodgkin lymphoma and chronic lymphocytic leukemia (CLL)

Acute and chronic leukemias and myeloproliferative neoplasms

Multiple myeloma (MM)