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Salvage Therapy 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: Wednesday, Apr 13, 2016


Transcript:

Stefan Faderl, MD:
There are a number of interesting new drugs you can use as salvage therapy in patients with acute lymphoblastic leukemia. Liposomal vincristine is a single myelin cholesterol-based nanoparticle formulation of vincristine, which really was designed based on dosing or pharmacokinetic restrictions with vincristine per se, but it relies on vincristine as the active drug. It has been approved a few years back by the FDA based on a single arm phase II study. I forgot the number of patients, but the response rate overall was about 35% with about 20% CR rate. The interesting part of the study is that all of those patients were exposed prior to regular type vincristine and about half of those patients actually sent for a stem cell transplant before they relapsed, so it has activity. I use it as a single agent less than in combination with steroids. It may be useful in some of those patients.

Blinatumomab is a newer addition to the choice of drugs in relapsed acute lymphoblastic leukemia. It’s a bispecific T-cell engager monoclonal antibody. The first immune therapy approved in acute lymphoblastic leukemia was in December of 2014 by the FDA, based on an exploratory or expanded phase II study of patients with poor prognosis relapsed/refractory acute lymphoblastic leukemia; 189 patients and the response rate in the study was about 40%. Actually a high number of those responding patients, about 70% to-75%, also achieved minimal residual disease-negative status after treatment.

Nelarabine is an older drug. It’s a purine nucleoside analog. You may look at it more as a traditional sort of chemotherapy drug. To be active, it requires conversion into its ara-GTP molecular structure, if you will. It’s a cytotoxic in a more traditional sense. It destroys DNA and it seems to be very active in T-cells as opposed to B-cells. It’s been approved in relapsed/refractory T-cell malignancy. It’s not necessarily restricted to T-cell acute lymphoblastic leukemia, but it also has some interest in frontline combinations in patients with T-cell acute lymphoblastic leukemia. Any one of those drugs has its role. It’s really almost impossible to say whether there is any ideal sequence in which to give those drugs. I think it’s way out there, there’s no study at all that you can rely on or base your opinion on, but all of these agents have activity and have their place.

There are also options of more traditional chemotherapy combinations of drugs, which are not necessarily used frontline. For instance, clofarabine is used in pediatric patients maybe more than in adult acute lymphoblastic leukemia. And there are chemotherapy combinations that may still have their value in some situations.

Transcript Edited for Clarity
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Transcript:

Stefan Faderl, MD:
There are a number of interesting new drugs you can use as salvage therapy in patients with acute lymphoblastic leukemia. Liposomal vincristine is a single myelin cholesterol-based nanoparticle formulation of vincristine, which really was designed based on dosing or pharmacokinetic restrictions with vincristine per se, but it relies on vincristine as the active drug. It has been approved a few years back by the FDA based on a single arm phase II study. I forgot the number of patients, but the response rate overall was about 35% with about 20% CR rate. The interesting part of the study is that all of those patients were exposed prior to regular type vincristine and about half of those patients actually sent for a stem cell transplant before they relapsed, so it has activity. I use it as a single agent less than in combination with steroids. It may be useful in some of those patients.

Blinatumomab is a newer addition to the choice of drugs in relapsed acute lymphoblastic leukemia. It’s a bispecific T-cell engager monoclonal antibody. The first immune therapy approved in acute lymphoblastic leukemia was in December of 2014 by the FDA, based on an exploratory or expanded phase II study of patients with poor prognosis relapsed/refractory acute lymphoblastic leukemia; 189 patients and the response rate in the study was about 40%. Actually a high number of those responding patients, about 70% to-75%, also achieved minimal residual disease-negative status after treatment.

Nelarabine is an older drug. It’s a purine nucleoside analog. You may look at it more as a traditional sort of chemotherapy drug. To be active, it requires conversion into its ara-GTP molecular structure, if you will. It’s a cytotoxic in a more traditional sense. It destroys DNA and it seems to be very active in T-cells as opposed to B-cells. It’s been approved in relapsed/refractory T-cell malignancy. It’s not necessarily restricted to T-cell acute lymphoblastic leukemia, but it also has some interest in frontline combinations in patients with T-cell acute lymphoblastic leukemia. Any one of those drugs has its role. It’s really almost impossible to say whether there is any ideal sequence in which to give those drugs. I think it’s way out there, there’s no study at all that you can rely on or base your opinion on, but all of these agents have activity and have their place.

There are also options of more traditional chemotherapy combinations of drugs, which are not necessarily used frontline. For instance, clofarabine is used in pediatric patients maybe more than in adult acute lymphoblastic leukemia. And there are chemotherapy combinations that may still have their value in some situations.

Transcript Edited for Clarity
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