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Case Report: Use of Larotrectinib in a Boy With TRK Fusion–Positive ALL

By: Joshua D. Madera, MS
Posted: Sunday, August 1, 2021

The selective TRK inhibitor larotrectinib may prove to be an effective treatment option for patients with ETV6-NRTK–positive B-cell acute lymphocytic leukemia (ALL), according to a case report published in Blood Advances. Treatment with larotrectinib and low-dose chemotherapy led to sustained molecular remission, reported Denis M. Schewe, MD, of University Hospital Schleswig-Holstein, Kiel, Germany, and colleagues.

The patient was a 6-year-old boy with B-cell ALL and central nervous system (CNS) infiltration who had previously received polychemotherapy. A peripheral blood sample that demonstrated hyperleukocytosis underwent fluorescence in situ hybridization and cytogenetic analysis. The findings revealed an unbalanced translocation of the ETV6 locus. After an ineffective treatment with prednisone and negative minimal residual disease (MRD) in the bone marrow, the decision was made to proceed with allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patient relapsed 50 days after transplantation, so RNA sequencing was performed. This analysis led to the detection of the ETV6-NRTK fusion protein.

The patient was administered 100 mg/m2 of larotrectinib twice daily in combination with intraventricular chemotherapy (2 mg of methotrexate and 1 mg of etoposide). Polymerase chain reaction revealed that this treatment regimen effectively induced molecular remission in the bone marrow and CNS. Larotrectinib treatment was arrested for T-cell apheresis, and chimeric antigen receptor (CAR) T-cell therapy was commenced. Although CAR T-cell therapy led to B-cell aplasia, the patient relapsed once again in the CNS. Therefore, larotrectinib treatment was reinitiated at a higher dose (150 mg/m2 twice daily), which led to remission.

“We conclude that MRD negativity in the bone marrow is primarily due to larotrectinib, and CAR T-cell therapy may also have contributed. In the CNS, a part of the antileukemic effect is certainly mediated by the low-dose chemotherapeutic agents,” explained Dr. Schewe and colleagues.

Disclosures: For full disclosures of the study authors, visit ashpublications.org.


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