Presenter Status
Fellow
Abstract Type
Case report
Primary Mentor
Karen Lewing MD
Start Date
9-5-2023 11:30 AM
End Date
9-5-2023 1:30 PM
Presentation Type
Poster Presentation
Description
Background: CBFA2T3::GLIS2-associated AML (CBF/GLIS AML) is an aggressive form of AML often associated with AMKL and recognized by its unique RAM phenotype by flow. It has a very poor prognosis, frequently refractory to standard of care regimens, with extreme marrow localization of leukemic blasts likely mediated by high CXCR4 (CD184) expression. The CBFA2T3::GLIS2 fusion gene is the most common oncogenic transcript in pediatric AMKL and universally results in high expression of FOLR1 surface antigen. STRO-002, an antibody drug conjugate targeting FOLR1, is currently in Phase I clinical trials for adults with refractory ovarian and endometrial malignancies A summary of 17 patients with refractory CBFA2T3::GLIS2 AML who received STRO-002 under compassionate use single patient IND reported significant clinical activity with little to no toxicity (7 patients achieved MRD negative remissions). Plerixafor, a reversible CXCR4 antagonist, mobilizes marrow stem cells and leukemic cells and has been investigated in patients with relapsed/refractory leukemia in combination with chemotherapy with modest response.
Objectives/Goal: We report a case of complete morphologic and immunophenotypic remission by targeted combination of STRO-002 and plerixafor in a child with refractory CBF/GLIS AML.
Methods/Design: Case Report
Results: A 2-year-old female presented with fever, arm pain, and bruising and was diagnosed with RAM phenotype AMKL with FOLR1-positive CBFA2T3::GLIS2 oncogenic fusion. She was enrolled on AAML1831 Arm A but Induction therapy was unsuccessful as evidenced by 14% residual BM blasts by flow cytometry. She was transitioned to STRO-002 monotherapy (4.3mg/kg/dose IV every 2 weeks) as an outpatient for 4 cycles. BM was assessed q2wks prior to each cycle. Flow results post Cycles 1-4 were respectively: 2.7%, 2.02%, 1.6%, and 0.36%. Given persistent measurable residual leukemia, Plerixafor was added for leukemic cell mobilization with Cycles 5 and 6 (Plerixafor 0.24mg/kg/dose 4h prior and 24h post each STRO-002 dose). After Cycle 5, MRD was 0.013% by flow and 0.4% CBFA2T3::GLIS2 fusion expression. After Cycle 6, our patient achieved 0% MRD by flow and 0% CBFA2T3::GLIS2 fusion expression. She had one episode of transient neutropenia after Cycle 5 while RSV+. Blood counts improved with the addition of plerixafor, and no toxicities were noted. She is currently 3 weeks statuspost haploidentical bone marrow transplant awaiting engraftment.
Conclusions: Our patient with refractory CBFA2T3::GLIS2-associated AMKL achieved CR with STRO-002 and further reduction in leukemic burden was observed when plerixafor was added in combination. The treatment was well-tolerated by our patient. This initial report of the STRO-002- plerixafor combination supports further evaluation in similar patients.
Included in
A Novel Therapy for Refractory CBFA2T3::GLIS2-associated AMKL Using STRO-002 And Plerixafor
Background: CBFA2T3::GLIS2-associated AML (CBF/GLIS AML) is an aggressive form of AML often associated with AMKL and recognized by its unique RAM phenotype by flow. It has a very poor prognosis, frequently refractory to standard of care regimens, with extreme marrow localization of leukemic blasts likely mediated by high CXCR4 (CD184) expression. The CBFA2T3::GLIS2 fusion gene is the most common oncogenic transcript in pediatric AMKL and universally results in high expression of FOLR1 surface antigen. STRO-002, an antibody drug conjugate targeting FOLR1, is currently in Phase I clinical trials for adults with refractory ovarian and endometrial malignancies A summary of 17 patients with refractory CBFA2T3::GLIS2 AML who received STRO-002 under compassionate use single patient IND reported significant clinical activity with little to no toxicity (7 patients achieved MRD negative remissions). Plerixafor, a reversible CXCR4 antagonist, mobilizes marrow stem cells and leukemic cells and has been investigated in patients with relapsed/refractory leukemia in combination with chemotherapy with modest response.
Objectives/Goal: We report a case of complete morphologic and immunophenotypic remission by targeted combination of STRO-002 and plerixafor in a child with refractory CBF/GLIS AML.
Methods/Design: Case Report
Results: A 2-year-old female presented with fever, arm pain, and bruising and was diagnosed with RAM phenotype AMKL with FOLR1-positive CBFA2T3::GLIS2 oncogenic fusion. She was enrolled on AAML1831 Arm A but Induction therapy was unsuccessful as evidenced by 14% residual BM blasts by flow cytometry. She was transitioned to STRO-002 monotherapy (4.3mg/kg/dose IV every 2 weeks) as an outpatient for 4 cycles. BM was assessed q2wks prior to each cycle. Flow results post Cycles 1-4 were respectively: 2.7%, 2.02%, 1.6%, and 0.36%. Given persistent measurable residual leukemia, Plerixafor was added for leukemic cell mobilization with Cycles 5 and 6 (Plerixafor 0.24mg/kg/dose 4h prior and 24h post each STRO-002 dose). After Cycle 5, MRD was 0.013% by flow and 0.4% CBFA2T3::GLIS2 fusion expression. After Cycle 6, our patient achieved 0% MRD by flow and 0% CBFA2T3::GLIS2 fusion expression. She had one episode of transient neutropenia after Cycle 5 while RSV+. Blood counts improved with the addition of plerixafor, and no toxicities were noted. She is currently 3 weeks statuspost haploidentical bone marrow transplant awaiting engraftment.
Conclusions: Our patient with refractory CBFA2T3::GLIS2-associated AMKL achieved CR with STRO-002 and further reduction in leukemic burden was observed when plerixafor was added in combination. The treatment was well-tolerated by our patient. This initial report of the STRO-002- plerixafor combination supports further evaluation in similar patients.
