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Gemtuzumab Ozogamicin Produces Durable Responses in Variant Acute Promyelocytic Leukemia with t(11;17)
Abstracts AML-179 Gemtuzumab Ozogamicin Produces Durable Responses in Variant Acute Promyelocytic Leukemia with t(11;17) Asha Balakrishnan ,1 Kendra Sweet,2 Rami Komrokji,2 David Sallman,2 Eric Padron,2 Alan List,2 Jeffrey Lancet2 1
Department of Internal Medicine, University of South Florida, Tampa,
FL, Tampa, FL, United States; 2Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, Tampa, FL, United States
Introduction: Acute promyelocytic leukemia (APL) rarely exhibits a variant t(11;17), which typically confers resistance to alltrans retinoic acid (ATRA) and carries a very poor prognosis. Gemtuzumab Ozogamicin (GO) is a conjugated drug antibody against CD33 that has been successfully used as a single agent for relapsed t(15;17) APL and in combination with ATRA + arsenic trioxide (ATO) as initial therapy. We present two patients with t(11;17) APL successfully treated with GO. Case Descriptions: Patient 1: 79 year old woman presented with fatigue, anemia, thrombocytopenia, and WBC 11.5 with 24% promyelocytes. Bone marrow biopsy (BMB) confirmed APL t(11;17)(q23;21). CD33 was highly expressed on the malignant cells. Due to poor functional status, she was deemed unfit for conventional chemotherapy and was treated with GO 9 mg/m2 on days 1 and 14. BMB day 48 confirmed complete remission (CR) with 4% blasts, normal cytogenetics, along with full count recovery. Functional status improved. She relapsed 19 months later and received a second course of GO, without response. Due to progression in central nervous system, patient expired shortly thereafter. Patient 2: 72 year old man presented with fatigue, pancytopenia, and BMB suggesting myelodysplastic syndrome (MDS). He became increasingly transfusion dependent despite treatment with 5-azacitidine and darbopoietin. Repeat BMB confirmed APL t(11;17)(q23;q21.1) with 80% atypical promyelocytes, CD33+ by flow cytometry. After induction with idarubicin and cytarabine, BMB day 28 revealed residual disease with 59% atypical promyelocytes. There was interval development of disseminated intravascular coagulation with extensive right gluteal and left ileopsoas hemorrhage. Salvage therapy with GO 6 mg/m2 was given on days 1 and 15, with subsequent CR documented at day 42, and resolution of hemorrhage. Relapse was documented 9 months later. Despite retreatment with GO (day 1 only), BMB day 26 showed residual disease by morphology, cytogenetics and FISH. Further salvage therapy included arsenic trioxide, decitabine, and ATRA, without
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effect. The patient eventually expired from an intracranial hemorrhage. Conclusions: GO appears to be highly active in the setting of APL with t(11;17). Further case details and literature review will be provided.
AML-183 Impact of Persistent Somatic Mutations on Day 14 After Induction Chemotherapy for Acute Myeloid Leukemia Kendra Sweet , Mohammad Hussaini, Jeffrey Lancet, Rami Komrokji, Alan List, Lynn Moscinski, Jinming Song, Eric Padron Moffitt Cancer Center, Tampa, FL, United States
Context: Residual AML on D14 after induction typically warrants re-induction. This decision is based on D14 cellularity and blast count, yet many with aplastic D14 marrows fail to achieve CR. Objective: To determine if persistent mutations at D14 predict CR and if this could guide decisions about re-induction. Design: Retrospective analysis of AML patients treated with induction. April 2015-2016. Setting: Academic Cancer Center Patients: AML patients treated with induction who had NGS panels prior to induction, at D14, and in some, at count recovery. Main Outcome Measures: D14 genetic profiles classified as favorable (mutation clearance; 20% decrease in any mutation VAF), unfavorable (unchanged NGS; 20% increase in any mutation VAF; new mutations) or ambiguous (no change in VUS). Responses classified as CR/CRi or treatment failure. Results: 37 patients. Median age 60 (28-78). 62% (n¼23) male. By D14, 25% (n¼9) cleared all mutations. D14 genetic profiles were favorable: 57% (n¼21); unfavorable: 11% (n¼4); ambiguous: 32% (n¼12). 86% (n¼32) achieved CR/Cri. 60% (n¼3) who failed treatment were unfavorable/ambiguous; 41% (n¼13) with CR/Cri unfavorable/ ambiguous. 65% (n¼24) aplastic at D14. 63% (n¼15) were genetically favorable (Table 1). At count recovery, 18 had NGS panels. 39% (n¼7) cleared all mutations. Reclassification at count recovery changed genetic category in some (Table 2). 73% (n¼8) with persistent mutations achieved CR/CRi versus 86% (n¼6) without mutations. No differences are statistically significant. Conclusion: Many AML-related mutations persist at D14, even in aplastic marrows. Mutational burden evolves between D14 and count recovery suggesting D14 may not be the optimal time to genetically determine the likelihood of CR. This provides rationale for kinetic analysis of mutational burden to identify the optimal predictive time for genetic analysis.
Department of Internal Medicine, University of South Florida, Tampa,
FL, Tampa, FL, United States; 2Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, Tampa, FL, United States
Introduction: Acute promyelocytic leukemia (APL) rarely exhibits a variant t(11;17), which typically confers resistance to alltrans retinoic acid (ATRA) and carries a very poor prognosis. Gemtuzumab Ozogamicin (GO) is a conjugated drug antibody against CD33 that has been successfully used as a single agent for relapsed t(15;17) APL and in combination with ATRA + arsenic trioxide (ATO) as initial therapy. We present two patients with t(11;17) APL successfully treated with GO. Case Descriptions: Patient 1: 79 year old woman presented with fatigue, anemia, thrombocytopenia, and WBC 11.5 with 24% promyelocytes. Bone marrow biopsy (BMB) confirmed APL t(11;17)(q23;21). CD33 was highly expressed on the malignant cells. Due to poor functional status, she was deemed unfit for conventional chemotherapy and was treated with GO 9 mg/m2 on days 1 and 14. BMB day 48 confirmed complete remission (CR) with 4% blasts, normal cytogenetics, along with full count recovery. Functional status improved. She relapsed 19 months later and received a second course of GO, without response. Due to progression in central nervous system, patient expired shortly thereafter. Patient 2: 72 year old man presented with fatigue, pancytopenia, and BMB suggesting myelodysplastic syndrome (MDS). He became increasingly transfusion dependent despite treatment with 5-azacitidine and darbopoietin. Repeat BMB confirmed APL t(11;17)(q23;q21.1) with 80% atypical promyelocytes, CD33+ by flow cytometry. After induction with idarubicin and cytarabine, BMB day 28 revealed residual disease with 59% atypical promyelocytes. There was interval development of disseminated intravascular coagulation with extensive right gluteal and left ileopsoas hemorrhage. Salvage therapy with GO 6 mg/m2 was given on days 1 and 15, with subsequent CR documented at day 42, and resolution of hemorrhage. Relapse was documented 9 months later. Despite retreatment with GO (day 1 only), BMB day 26 showed residual disease by morphology, cytogenetics and FISH. Further salvage therapy included arsenic trioxide, decitabine, and ATRA, without
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effect. The patient eventually expired from an intracranial hemorrhage. Conclusions: GO appears to be highly active in the setting of APL with t(11;17). Further case details and literature review will be provided.
AML-183 Impact of Persistent Somatic Mutations on Day 14 After Induction Chemotherapy for Acute Myeloid Leukemia Kendra Sweet , Mohammad Hussaini, Jeffrey Lancet, Rami Komrokji, Alan List, Lynn Moscinski, Jinming Song, Eric Padron Moffitt Cancer Center, Tampa, FL, United States
Context: Residual AML on D14 after induction typically warrants re-induction. This decision is based on D14 cellularity and blast count, yet many with aplastic D14 marrows fail to achieve CR. Objective: To determine if persistent mutations at D14 predict CR and if this could guide decisions about re-induction. Design: Retrospective analysis of AML patients treated with induction. April 2015-2016. Setting: Academic Cancer Center Patients: AML patients treated with induction who had NGS panels prior to induction, at D14, and in some, at count recovery. Main Outcome Measures: D14 genetic profiles classified as favorable (mutation clearance; 20% decrease in any mutation VAF), unfavorable (unchanged NGS; 20% increase in any mutation VAF; new mutations) or ambiguous (no change in VUS). Responses classified as CR/CRi or treatment failure. Results: 37 patients. Median age 60 (28-78). 62% (n¼23) male. By D14, 25% (n¼9) cleared all mutations. D14 genetic profiles were favorable: 57% (n¼21); unfavorable: 11% (n¼4); ambiguous: 32% (n¼12). 86% (n¼32) achieved CR/Cri. 60% (n¼3) who failed treatment were unfavorable/ambiguous; 41% (n¼13) with CR/Cri unfavorable/ ambiguous. 65% (n¼24) aplastic at D14. 63% (n¼15) were genetically favorable (Table 1). At count recovery, 18 had NGS panels. 39% (n¼7) cleared all mutations. Reclassification at count recovery changed genetic category in some (Table 2). 73% (n¼8) with persistent mutations achieved CR/CRi versus 86% (n¼6) without mutations. No differences are statistically significant. Conclusion: Many AML-related mutations persist at D14, even in aplastic marrows. Mutational burden evolves between D14 and count recovery suggesting D14 may not be the optimal time to genetically determine the likelihood of CR. This provides rationale for kinetic analysis of mutational burden to identify the optimal predictive time for genetic analysis.