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Optimizing Blinatumomab Use in Acute Lymphoblastic Leukemia

Insights From:Stefan Faderl, MD, John Theurer Cancer Center; Raoul Tibes, MD, PhD, Mayo Clinic; Bijal D. Shah, MD, Moffitt Cancer Center
Published: Thursday, Mar 17, 2016


Transcript:

Stefan Faderl, MD:
What is the optimal use of blinatumomab in ALL? Currently, it’s mainly used as a single agent the way it’s been FDA labeled and approved in relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia. In my personal experience, we’ve been using it quite extensively in relapsed settings. My personal experience somehow reflects the published data, and I’m actually quite happy with some of the results in some patients with blinatumomab. It’s certainly correct to assume that down the road, blinatumomab may not be isolated in that setting. I don’t see it so much as a frontline drug at the time of diagnosis. One problem with blinatumomab or with immunotherapy in general-you can expand that to the CAR T-cell programs as well - is that they are not easy to use in patients with a high tumor load, patients who present with a high white cell count who have a lot of disease in other organs, a toxicity can become quite significant. It’s usually better to use those agents after some sort of debulking regimen prior to it, but it does not have to be particularly intense. It can just consist of steroids or steroids plus cyclophosphamide. But in some sequential fashion you could indeed think about the use of blinatumomab following some intensive chemotherapy induction, hyper-CVAD one or two cycles and then sequentially use blinatumomab to mop up residual disease and solidify a response. You can even think that you may not need such intensive induction regimens to start with and that you could get away with low intensity regimens, which may be a more attractive option in elderly patients who suffer more from toxicities of intensive chemotherapy at any rate.

Blinatumomab is an effective drug in eliminating minimal residual disease. In that sense, it may very well have a role prior to hematopoietic stem cell transplant, as plenty of data have shown and continue to show that patients do best after a transplant, who go into transplant with no evidence of minimal residual disease as opposed to still have evidence of it. You may look at it as a possible consolidation maintenance treatment after transplant. It’s certainly a possibility as well. I’ve even heard people say that they use it as sort of a “debulking therapy” prior to a CAR T-cell therapy. There are plenty of opportunities of using blinatumomab in any of those settings.

There was evidence presented at the ASH meeting in 2015 as well, that blinatumomab is also active in patients with Philadelphia chromosome-positive disease. This was a study of45 patients. The median age was about 55 years. All of those patients had relapsed/refractory disease and actually quite extensive exposure to a number of kinase inhibitors, second and third-generation kinase inhibitors. A good number of those patients had a prior stem cell transplant and then a few of those patients even had the usually highly resistant T315I mutation. What the results showed was activity comparable to the one established in Philadelphia chromosome-negative disease with a response rate of around 40%. More interestingly, the response rate holds up in that range of 35%-40% if you look at subtypes of patients. For instance, those with T315I mutations or those with at least two or more second-generation kinase inhibitors prior to getting blinatumomab.

There’s also a substantial rate of minimal residual disease negativity at about 80% and relapse-free survival, disease-free survival comparable to what’s been established in previous studies of PH-negative disease. I think it is a very active drug in PH-positive disease and it should be approved for that indication as well.

Transcript Edited for Clarity
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Transcript:

Stefan Faderl, MD:
What is the optimal use of blinatumomab in ALL? Currently, it’s mainly used as a single agent the way it’s been FDA labeled and approved in relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia. In my personal experience, we’ve been using it quite extensively in relapsed settings. My personal experience somehow reflects the published data, and I’m actually quite happy with some of the results in some patients with blinatumomab. It’s certainly correct to assume that down the road, blinatumomab may not be isolated in that setting. I don’t see it so much as a frontline drug at the time of diagnosis. One problem with blinatumomab or with immunotherapy in general-you can expand that to the CAR T-cell programs as well - is that they are not easy to use in patients with a high tumor load, patients who present with a high white cell count who have a lot of disease in other organs, a toxicity can become quite significant. It’s usually better to use those agents after some sort of debulking regimen prior to it, but it does not have to be particularly intense. It can just consist of steroids or steroids plus cyclophosphamide. But in some sequential fashion you could indeed think about the use of blinatumomab following some intensive chemotherapy induction, hyper-CVAD one or two cycles and then sequentially use blinatumomab to mop up residual disease and solidify a response. You can even think that you may not need such intensive induction regimens to start with and that you could get away with low intensity regimens, which may be a more attractive option in elderly patients who suffer more from toxicities of intensive chemotherapy at any rate.

Blinatumomab is an effective drug in eliminating minimal residual disease. In that sense, it may very well have a role prior to hematopoietic stem cell transplant, as plenty of data have shown and continue to show that patients do best after a transplant, who go into transplant with no evidence of minimal residual disease as opposed to still have evidence of it. You may look at it as a possible consolidation maintenance treatment after transplant. It’s certainly a possibility as well. I’ve even heard people say that they use it as sort of a “debulking therapy” prior to a CAR T-cell therapy. There are plenty of opportunities of using blinatumomab in any of those settings.

There was evidence presented at the ASH meeting in 2015 as well, that blinatumomab is also active in patients with Philadelphia chromosome-positive disease. This was a study of45 patients. The median age was about 55 years. All of those patients had relapsed/refractory disease and actually quite extensive exposure to a number of kinase inhibitors, second and third-generation kinase inhibitors. A good number of those patients had a prior stem cell transplant and then a few of those patients even had the usually highly resistant T315I mutation. What the results showed was activity comparable to the one established in Philadelphia chromosome-negative disease with a response rate of around 40%. More interestingly, the response rate holds up in that range of 35%-40% if you look at subtypes of patients. For instance, those with T315I mutations or those with at least two or more second-generation kinase inhibitors prior to getting blinatumomab.

There’s also a substantial rate of minimal residual disease negativity at about 80% and relapse-free survival, disease-free survival comparable to what’s been established in previous studies of PH-negative disease. I think it is a very active drug in PH-positive disease and it should be approved for that indication as well.

Transcript Edited for Clarity
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