New Therapies Making a Big Impact in ALL

Daniel A. Pollyea, MD, MS, University of Colorado School of Medicine, Denver, discusses novel therapies for acute lymphoblastic leukemia (ALL) and how they are changing clinical practice.

Daniel A. Pollyea, MD, MS: ALL historically in the adult population has been just a brutal disease. We have had very little success in getting patients cured or to long-term improvements in survival, and that's really changing thanks to some really exciting new treatments.

For the last couple years we've had a liposomal vincristine, which can be given as a single agent for relapse/refractory patients, and may have some better tolerability than regular vincristine and has some activity in the relapse/refractory setting.

For patients with relapsed T-cell ALL, nelarabine, which is a nucleotide analogue, has some activity and is certainly a well-considered option. Most of the really exciting new therapies in ALL have been various ways to harness a patient's immune system to help attack and destroy the leukemia cells.

We have now inotuzumab, which is an antibody drug conjugate that exploits CD22, which has been a really effective therapy for relapse patients when compared to traditional chemotherapy has shown superiority with respect to survival.

There's also blinatumomab, which is a really novel therapy that combines a way to attack CD19, which is frequently expressed in the pre-B cell -- so pretty much all ALL patients with B-cell ALL will exploit CD19 -- in combination with a CD3-targeting modality that allows for the target cells -- the CD19 leukemia cells -- to be brought into close proximity to T-cells and in that way attacked and destroyed.

This is an approved therapy for relapse/refractory B-cell ALL and for patients in a remission who have measurable residual disease to try to clean up some of that disease maybe prior to a transplant or just to deepen a response. That's really exciting as well.

Finally we have this incredible new therapy, which we call CAR T therapies, which are ways to personalize the therapy, attack and destroy the patient's tumor using their own T-cells. We remove the T-cells from the patient. We infect them with a virus that will allow them to change and attack and destroy the tumor cells and then reinfuse those T-cells into the blood and allow for the patient's own T-cells to be reoriented toward the patient's tumor.

This is just an incredible therapy that's resulting in a higher response rate in the relapse/refractory setting than any other known therapy. There are versions of this that are now approved and others that are surely soon to be approved.

In the ALL landscape, we've come so far and really the sky seems to be the limit for what we can achieve.