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Transplant for Chronic Myeloid Leukemia

Insights From: Kendra Sweet, MD, Moffitt Cancer Center; Naval Daver, MD, University of Texas MD Anderson Cancer Center; Javier Pinilla-Ibarz, MD, PhD, Moffitt Cancer Center
Published Online: Monday, Apr 10, 2017



Transcript:

Kendra Sweet, MD:
When I start someone on second-line therapy, I start monitoring them again in the same way that I did or do when they’re on their first-line therapy. When transplant starts coming into my mind, it’s really at the time that they show that they’re failing second-line therapy. If they fail to reach a milestone at 3 months, that’s a time that I would consider sending someone for a transplant evaluation. I’m not always saying this person needs to go to transplant immediately, but at least get their foot in the door, meet the transplanter, and possibly search for a donor. So, at any point when they are not responding the way that we would hope, meeting those specific milestones at specific time points, that’s when I would say, “It’s time to look into, or at least consider, transplant.”

I consider a transplant in somebody who has, of course, progressed to accelerated phase CML or a blast-phase CML. In that setting, a transplant, in my mind, would always be indicated if the patient is appropriate and if a suitable donor is available. In regards to chronic-phase CML patients, transplant would be appropriate, in my opinion, when they have shown that they failed 2, possibly 3, TKIs, especially if someone has already failed ponatinib. If someone has failed ponatinib, that, to me, is an indication that transplant is definitely needed. If they failed imatinib and 1 second-generation TKI, depending on the scenario, I may try another second-generation TKI or ponatinib before really pushing for transplant. But absolutely, at any point, if someone has failed 3 TKIs, I think a transplant needs to be seriously looked into, but I would refer them at the time that we’d be switching to third-line therapy.

The best time to do the transplant would obviously be before someone has progressed to an advanced phase of CML. So, if we can transplant patients while they’re still in the chronic phase, their long-term outcomes are going to be better and the benefit of transplant is certainly going to be higher. In my mind, getting someone to transplant when we start to see that they’re failing second-line or third-line therapy is the best time to get them there, not waiting until they’ve progressed or have failed all 5 TKIs. We actually have our own data from Moffitt Cancer Center that show that prior TKI therapy doesn’t have any impact on outcomes with transplant. We looked at a number of our patients who’ve gone to transplant in the last 15 years after being treated with TKIs, and 1 versus 2 versus 3 or 4 TKIs didn’t seem to have any impact on outcomes.

When I have a patient who has not achieved an adequate response to therapy, if it’s their first-line TKI, you’ll need to look at a mutation analysis, we need to look for possible drug interactions, and we need to talk about adherence to their medication schedule. And if we’re not finding an obvious reason for failure to respond, then we need to consider changing treatment. At any point that someone is not meeting a milestone, that’s when we need to start looking into the potential for changing treatment. In regard to patients who relapse after a transplant, that’s a much more difficult situation. But the one nice thing about CML is that it’s often very responsive to a donor lymphocyte infusion (DLI). So, if we can get a patient to a DLI, we have a fairly good likelihood of salvaging that patient. If it’s a patient with advanced-phase CML, it would certainly be ideal to get them back into chronic phase before doing a DLI. But there is good success with DLI in CML, so that’s definitely an approach that I would recommend or that I would take in that setting. In addition to that, I think getting a patient back on a TKI at the time that they relapse is really important.

Transcript Edited for Clarity
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Transcript:

Kendra Sweet, MD:
When I start someone on second-line therapy, I start monitoring them again in the same way that I did or do when they’re on their first-line therapy. When transplant starts coming into my mind, it’s really at the time that they show that they’re failing second-line therapy. If they fail to reach a milestone at 3 months, that’s a time that I would consider sending someone for a transplant evaluation. I’m not always saying this person needs to go to transplant immediately, but at least get their foot in the door, meet the transplanter, and possibly search for a donor. So, at any point when they are not responding the way that we would hope, meeting those specific milestones at specific time points, that’s when I would say, “It’s time to look into, or at least consider, transplant.”

I consider a transplant in somebody who has, of course, progressed to accelerated phase CML or a blast-phase CML. In that setting, a transplant, in my mind, would always be indicated if the patient is appropriate and if a suitable donor is available. In regards to chronic-phase CML patients, transplant would be appropriate, in my opinion, when they have shown that they failed 2, possibly 3, TKIs, especially if someone has already failed ponatinib. If someone has failed ponatinib, that, to me, is an indication that transplant is definitely needed. If they failed imatinib and 1 second-generation TKI, depending on the scenario, I may try another second-generation TKI or ponatinib before really pushing for transplant. But absolutely, at any point, if someone has failed 3 TKIs, I think a transplant needs to be seriously looked into, but I would refer them at the time that we’d be switching to third-line therapy.

The best time to do the transplant would obviously be before someone has progressed to an advanced phase of CML. So, if we can transplant patients while they’re still in the chronic phase, their long-term outcomes are going to be better and the benefit of transplant is certainly going to be higher. In my mind, getting someone to transplant when we start to see that they’re failing second-line or third-line therapy is the best time to get them there, not waiting until they’ve progressed or have failed all 5 TKIs. We actually have our own data from Moffitt Cancer Center that show that prior TKI therapy doesn’t have any impact on outcomes with transplant. We looked at a number of our patients who’ve gone to transplant in the last 15 years after being treated with TKIs, and 1 versus 2 versus 3 or 4 TKIs didn’t seem to have any impact on outcomes.

When I have a patient who has not achieved an adequate response to therapy, if it’s their first-line TKI, you’ll need to look at a mutation analysis, we need to look for possible drug interactions, and we need to talk about adherence to their medication schedule. And if we’re not finding an obvious reason for failure to respond, then we need to consider changing treatment. At any point that someone is not meeting a milestone, that’s when we need to start looking into the potential for changing treatment. In regard to patients who relapse after a transplant, that’s a much more difficult situation. But the one nice thing about CML is that it’s often very responsive to a donor lymphocyte infusion (DLI). So, if we can get a patient to a DLI, we have a fairly good likelihood of salvaging that patient. If it’s a patient with advanced-phase CML, it would certainly be ideal to get them back into chronic phase before doing a DLI. But there is good success with DLI in CML, so that’s definitely an approach that I would recommend or that I would take in that setting. In addition to that, I think getting a patient back on a TKI at the time that they relapse is really important.

Transcript Edited for Clarity
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