TKI + Inotuzumab: Could This Be a Better Treatment? | Anand Patel, MD

Hi, my name is Anand Patel. I am part of the Acute Leukemia and Myeloid Malignancy Program at the University of Chicago. I’m going to discuss the results from our phase two study looking at the drug inotuzumab combined with tyrosine kinase inhibitors for Philadelphia chromosome-positive acute lymphoblastic leukemia, or Ph+ ALL. Ph+ ALL is seen in about 50% of B-cell ALL cases, especially in patients over the age of 50.

We’ve made significant progress in treating Ph+ ALL, particularly with tyrosine kinase inhibitors. When these drugs are combined with antibody-based therapies, outcomes are excellent, with remission rates upwards of 90% and long-term survival without needing a stem cell transplant.

Our study specifically looked at combining tyrosine kinase inhibitors with the antibody drug conjugate inotuzumab, which is given as an IV infusion once a week for three weeks per cycle. We enrolled 21 adults with newly diagnosed Ph+ ALL. Patients received the tyrosine kinase inhibitor dasatinib along with inotuzumab, and we monitored remission rates after two cycles, with the goal of deepening remission after three cycles.

Remission was measured in two ways: BCR-ABL PCR, which detects 1 in 10,000 leukemia cells, and next-generation sequencing, which detects 1 in 1,000,000 leukemia cells. By both methods, 19 out of 21 patients, or 90%, achieved measurable residual disease (MRD) negativity within three cycles of therapy.

With long-term follow-up, at the two-year mark, 80% of patients were still alive. Only one patient experienced a relapse, and no patients had central nervous system relapses. Importantly, none of the patients required a stem cell transplant.

In summary, this regimen is highly effective and safe, with appropriate dose adjustments. It compares very favorably to other published data using tyrosine kinase inhibitors and immunotherapy drugs like blinatumomab.

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