Contributions
Abstract: PB1364
Type: Publication Only
Session title: Acute lymphoblastic leukemia - Clinical
Background
Vyxeos is a liposomal formulation employing a 1:5 molar ratio of daunorubicin:cytarabine. Clinical trials in high risk acute myeloid leukemias demonstrated a significant benefit in CR rates and median OS, culminating in FDA approval August 2017. Emerging pediatric data suggest this benefit may extend to acute lymphoblastic leukemia (ALL).
Aims
The following pilot trial was performed to better understand the activity and toxicity profile in adults with relapsed and refractory ALL.
Methods
Adults with ALL or mixed phenotype leukemia were eligible if >5% lymphoblasts and/or extramedullary disease >1x1cm. Induction consisted of Vyxeos 100 units/m2 on days 1, 3 and 5. Those with clinical benefit could receive up to 3 cycles of consolidation delivered at 65 units/m2 on days 1 & 3 after recovery of neutrophils (>500 cells/μL) and platelets (>50,000 cells/μL).
Results
Ten patients have been treated to date, with median age of 40y (22-74y), 8 male, and 3 caucasian. Six had B-ALL, including 1 B-myeloid. Three of 4 T-ALL had early t-cell precursor (ETP) phenotype. NGS was available in 9, and include TP53 mutation (n=4), and PH-like changes (n=2). Median prior lines was 3, with 6 showing primary refractory disease. Prior blinatumomab, inotuzumab, CAR-T cell therapy, and allogeneic transplant were noted in 5, 2, 1, and 2 patients.
Pancytopenia was uniform during induction, with febrile neutropenia noted in 8. One passed from pneumonia after moving to comfort measures in lieu of intubation 20 days after Vyxeos, and is non-evaluable for response. A second patient developed grade 3 sepsis. The remainder of infections were grade 1-2. One had grade 3 gastrointestinal bleed, and 3 had grade 1 spontaneous subdural bleeding. One case of veno-occlusive disease was observed in a patient with prior allogeneic transplant and inotuzumab. Median time to ANC recovery was 32 days among 9 evaluable. Two with refractory disease failed to recover platelets; among the remaining 7, median time to platelet recovery was 30 days. Adverse events were uncommon during consolidation, and include foot cellulitis and myopericarditis, each in 1.
Among 9 evaluable patients, 3 achieved CR/CRi, including 2 ETP T-ALL and one B-ALL. Two with TP53 mutation demonstrated >50% blast reduction with hematologic recovery, allowing for prolonged time to subsequent therapy. Three received 1-3 cycles consolidation. One was bridged to donor leukocyte infusion. Responses were noted in only 2 after progression following Vyxeos. Median PFS was 28 days, time to next therapy 76 days, and OS 189 days.
Conclusion
Vyxeos in high risk refractory adult ALL was overall well tolerated and active, with median OS of approximately 6mo. A second induction course or the addition of novel agents may further improve on remission rates and duration of response.
Keyword(s): Acute lymphoblastic leukemia, Chemotherapy
Abstract: PB1364
Type: Publication Only
Session title: Acute lymphoblastic leukemia - Clinical
Background
Vyxeos is a liposomal formulation employing a 1:5 molar ratio of daunorubicin:cytarabine. Clinical trials in high risk acute myeloid leukemias demonstrated a significant benefit in CR rates and median OS, culminating in FDA approval August 2017. Emerging pediatric data suggest this benefit may extend to acute lymphoblastic leukemia (ALL).
Aims
The following pilot trial was performed to better understand the activity and toxicity profile in adults with relapsed and refractory ALL.
Methods
Adults with ALL or mixed phenotype leukemia were eligible if >5% lymphoblasts and/or extramedullary disease >1x1cm. Induction consisted of Vyxeos 100 units/m2 on days 1, 3 and 5. Those with clinical benefit could receive up to 3 cycles of consolidation delivered at 65 units/m2 on days 1 & 3 after recovery of neutrophils (>500 cells/μL) and platelets (>50,000 cells/μL).
Results
Ten patients have been treated to date, with median age of 40y (22-74y), 8 male, and 3 caucasian. Six had B-ALL, including 1 B-myeloid. Three of 4 T-ALL had early t-cell precursor (ETP) phenotype. NGS was available in 9, and include TP53 mutation (n=4), and PH-like changes (n=2). Median prior lines was 3, with 6 showing primary refractory disease. Prior blinatumomab, inotuzumab, CAR-T cell therapy, and allogeneic transplant were noted in 5, 2, 1, and 2 patients.
Pancytopenia was uniform during induction, with febrile neutropenia noted in 8. One passed from pneumonia after moving to comfort measures in lieu of intubation 20 days after Vyxeos, and is non-evaluable for response. A second patient developed grade 3 sepsis. The remainder of infections were grade 1-2. One had grade 3 gastrointestinal bleed, and 3 had grade 1 spontaneous subdural bleeding. One case of veno-occlusive disease was observed in a patient with prior allogeneic transplant and inotuzumab. Median time to ANC recovery was 32 days among 9 evaluable. Two with refractory disease failed to recover platelets; among the remaining 7, median time to platelet recovery was 30 days. Adverse events were uncommon during consolidation, and include foot cellulitis and myopericarditis, each in 1.
Among 9 evaluable patients, 3 achieved CR/CRi, including 2 ETP T-ALL and one B-ALL. Two with TP53 mutation demonstrated >50% blast reduction with hematologic recovery, allowing for prolonged time to subsequent therapy. Three received 1-3 cycles consolidation. One was bridged to donor leukocyte infusion. Responses were noted in only 2 after progression following Vyxeos. Median PFS was 28 days, time to next therapy 76 days, and OS 189 days.
Conclusion
Vyxeos in high risk refractory adult ALL was overall well tolerated and active, with median OS of approximately 6mo. A second induction course or the addition of novel agents may further improve on remission rates and duration of response.
Keyword(s): Acute lymphoblastic leukemia, Chemotherapy