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Expert Anticipates Cure in Acute Lymphoblastic Leukemia

Jason Harris
Published: Thursday, Aug 30, 2018

In addition, we have inotuzumab ozogamicin which is an anti-CD22 plus ozogamicin. We explored this drug at The University of Texas MD Anderson Cancer Center on a single-arm trial. We have explored different schedules and reported that the weekly regimen is better, safer, and as effective. That led to a trial called INO-VATE. Patients were randomized to receive either standard of care or inotuzumab ozogamicin given on a weekly schedule. There was an 80% response rate favoring the treatment with inotuzumab ozogamicin compared with 30% for standard of care. There was a high rate of MRD negativity with a high rate of survival as well; we have a survival rate of 23% compared with 10% for standard of care. Based on these data, the drug was approved for patients with relapsed/refractory ALL.

Finally, we have CAR T-cell therapies. We collect cells from a donor, engineer them, and send them back to attack the B-cell marker CD19. This has shown good activity in lymphoid malignancies, chronic lymphocytic leukemia, and ALL; however, here in ALL, we had very good responses. Patients with less disease burden had a better outcome because they had less [adverse events], including cytokine release syndrome and neurologic events. We have seen patients doing well in the long run, mainly those with minimal disease.

There was a trial sponsored by Novartis in collaboration with the University of Pennsylvania called ELIANA. It's a multicenter trial that led to approval in patients up to the age of 25 who have failed multiple lines of therapy.

In the same line of immunotherapy, investigators at Memorial Sloan Kettering Cancer Center explored pembrolizumab in adults with ALL. There was some toxicity, but there were some good responses as well, including some that were durable, mainly in patients with minimal disease.

The field is evolving. We're exploring a new generation of CAR T cells and we're moving into earlier relapses rather than later relapses.

What are the biggest challenges in treating ALL?

These drugs are very effective, but I don't think that using them in [later lines of therapy] is where the money is. We need to use these drugs upfront in the first salvage setting. We're exploring these drugs in a frontline setting because when we can improve outcomes on a larger scale, then we can…try to use them in combination with different agents. For example, with blinatumomab and inotuzumab ozogamicin, there are data showing that we can combine them together with chemotherapy and further improve outcomes. One of the challenges is that ALL is a rare disease. Community physicians should refer these patients to big institutions until they are familiar with the drugs.

The challenges that remain to be addressed are two-fold: it would be nice to have a drug with a long half-life that could be administered in a better way rather than over 4 weeks or 6 weeks. Finally, try to move CAR T cells earlier than later and have a safer product.

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Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 14th Annual International Symposium on Melanoma and Other Cutaneous Malignancies®Apr 30, 20192.0
Oncology Consultations®: The Advancing Role of CAR T-Cell Therapies in Hematologic MalignanciesApr 30, 20191.5
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