TY - JOUR
T1 - Phase 1/2 study of CPX-351 for patients with Int-2 or high risk International Prognostic Scoring System myelodysplastic syndromes and chronic myelomonocytic leukaemia after failure to hypomethylating agents
AU - Montalban-Bravo, Guillermo
AU - Jabbour, Elias
AU - Borthakur, Gautam
AU - Kadia, Tapan
AU - Ravandi, Farhad
AU - Chien, Kelly
AU - Pemmaraju, Naveen
AU - Hammond, Danielle
AU - Dong, Xiao Qin
AU - Huang, Xuelin
AU - Schneider, Heather
AU - John, Rosmy
AU - Kanagal-Shamana, Rashmi
AU - Loghavi, Sanam
AU - Kantarjian, Hagop
AU - Garcia-Manero, Guillermo
N1 - Publisher Copyright:
© 2023 British Society for Haematology and John Wiley & Sons Ltd.
PY - 2024/3
Y1 - 2024/3
N2 - Failure after hypomethylating agents (HMAs) is associated with dismal outcomes in higher risk myelodysplastic syndromes (HR-MDS) or chronic myelomonocytic leukaemia (CMML). We aimed to evaluate the safety and preliminary activity of lower doses of CPX-351, a liposomal encapsulation of cytarabine and daunorubicin, in a single-centre, phase 1/2 study for patients with HR-MDS or CMML after HMA failure. Four doses of CPX-351 (10, 25, 50 and 75 units/m2) administered on Days 1, 3 and 5 of induction and Days 1 and 3 of consolidation were evaluated. Between June 2019 and June 2023, 25 patients were enrolled (phase 1: n = 15; phase 2: n = 10) including 19 (76%) with HR-MDS and 6 (24%) with CMML. Most common grade 3–4 non-haematological treatment-emergent adverse events were febrile neutropenia (n = 12, 48%) and lung infection (n = 5, 20%). Three patients (age >75) experienced cardiac toxicity at the 75 units/m2 dose. Further enrolment continued at 50 units/m2. Four- and 8-week mortality were 0% and 8% respectively. The overall response rate was 56% with median relapse-free and overall survivals of 9.2 (95% CI 3.2–15.1 months) and 8.7 months (95% CI 1.8–15.6 months) respectively. These data suggest that lower doses of CPX-351 are safe. Further studies are needed to evaluate its activity.
AB - Failure after hypomethylating agents (HMAs) is associated with dismal outcomes in higher risk myelodysplastic syndromes (HR-MDS) or chronic myelomonocytic leukaemia (CMML). We aimed to evaluate the safety and preliminary activity of lower doses of CPX-351, a liposomal encapsulation of cytarabine and daunorubicin, in a single-centre, phase 1/2 study for patients with HR-MDS or CMML after HMA failure. Four doses of CPX-351 (10, 25, 50 and 75 units/m2) administered on Days 1, 3 and 5 of induction and Days 1 and 3 of consolidation were evaluated. Between June 2019 and June 2023, 25 patients were enrolled (phase 1: n = 15; phase 2: n = 10) including 19 (76%) with HR-MDS and 6 (24%) with CMML. Most common grade 3–4 non-haematological treatment-emergent adverse events were febrile neutropenia (n = 12, 48%) and lung infection (n = 5, 20%). Three patients (age >75) experienced cardiac toxicity at the 75 units/m2 dose. Further enrolment continued at 50 units/m2. Four- and 8-week mortality were 0% and 8% respectively. The overall response rate was 56% with median relapse-free and overall survivals of 9.2 (95% CI 3.2–15.1 months) and 8.7 months (95% CI 1.8–15.6 months) respectively. These data suggest that lower doses of CPX-351 are safe. Further studies are needed to evaluate its activity.
KW - CMML
KW - MDS
KW - clinical trials
KW - therapy
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U2 - 10.1111/bjh.19193
DO - 10.1111/bjh.19193
M3 - Article
C2 - 37946611
AN - SCOPUS:85176565901
SN - 0007-1048
VL - 204
SP - 898
EP - 909
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 3
ER -