JAMA oncology · 2018
Salvage Chemoimmunotherapy With Inotuzumab Ozogamicin Combined With Mini-Hyper-CVD for Patients With Relapsed or Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: A Phase 2 Clinical Trial.
Клиническое исследование II фазыСтатьяНазвание и аннотация: Перевод пока не подготовлен
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Jabbour Elias, Ravandi Farhad, Kebriaei Partow, Huang Xuelin, Short Nicholas J, Thomas Deborah, Sasaki Koji, Rytting Michael, Jain Nitin, Konopleva Marina, Garcia-Manero Guillermo, Champlin Richard, Marin David, Kadia Tapan, Cortes Jorge, Estrov Zeev, Takahashi Koichi, Patel Yogin, Khouri Maria R, Jacob Jovitta, Garris Rebecca, O'Brien Susan, Kantarjian Hagop
Аннотация
IMPORTANCE: The outcome of patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has single-agent activity in R/R ALL.
OBJECTIVE: To evaluate the efficacy and safety of inotuzumab ozogamicin plus low-intensity chemotherapy in patients with R/R ALL.
DESIGN, SETTING, AND PARTICIPANTS: A single-arm, phase 2 study of adults with R/R B-cell ALL conducted at The University of Texas MD Anderson Cancer Center, Houston.
INTERVENTIONS: The chemotherapy used was lower intensity than hyper-CVAD (cyclophosphamide, vincristine, doxorubicin [trade name, Adriamycin; Pfizer], and dexamethasone) and is referred to as mini-hyper-CVD (mini-HCVD: cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine at 0.5 g/m2 × 4 doses). Inotuzumab was given on day 3 of the first 4 courses at 1.8 to 1.3 mg/m2 for cycle 1 followed by 1.3 to 1.0 mg/m2 for subsequent cycles.
MAIN OUTCOMES AND MEASURES: The primary end points were the overall response rate and overall survival (OS). Secondary end points included safety, relapse-free survival (RFS), the rate of allogeneic stem cell transplantation (ASCT), and the minimal residual disease (MRD) negativity rate.
RESULTS: Fifty-nine patients (30 women and 29 men) with a median age of 35 years (range, 18-87 years) were treated. Overall, 46 patients (78%) responded, 35 of them (59%) achieving complete response. The overall MRD negativity rate among responders was 82%. Twenty-six patients (44%) received ASCT. Grade 3 to 4 toxic effects included prolonged thrombocytopenia (81%; n = 48), infections (73%; n = 43), and hyperbilirubinemia (14%; n = 8). Veno-occlusive disease (VOD) occurred in 9 patients (15%). With a median follow-up of 24 months, the median RFS and OS were 8 and 11 months, respectively. The 1-year RFS and OS rates were 40% and 46%, respectively. The 1-year OS rates for patients treated in salvage 1, salvage 2, and salvage 3 or beyond were 57%, 26%, and 39%, respectively (P = .03).
CONCLUSIONS AND RELEVANCE: The combination of inotuzumab with low-intensity mini-HCVD chemotherapy shows encouraging results in R/R ALL. The risk of VOD should be considered carefully in patients with previous liver damage and among transplant candidates.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01371630.
OBJECTIVE: To evaluate the efficacy and safety of inotuzumab ozogamicin plus low-intensity chemotherapy in patients with R/R ALL.
DESIGN, SETTING, AND PARTICIPANTS: A single-arm, phase 2 study of adults with R/R B-cell ALL conducted at The University of Texas MD Anderson Cancer Center, Houston.
INTERVENTIONS: The chemotherapy used was lower intensity than hyper-CVAD (cyclophosphamide, vincristine, doxorubicin [trade name, Adriamycin; Pfizer], and dexamethasone) and is referred to as mini-hyper-CVD (mini-HCVD: cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine at 0.5 g/m2 × 4 doses). Inotuzumab was given on day 3 of the first 4 courses at 1.8 to 1.3 mg/m2 for cycle 1 followed by 1.3 to 1.0 mg/m2 for subsequent cycles.
MAIN OUTCOMES AND MEASURES: The primary end points were the overall response rate and overall survival (OS). Secondary end points included safety, relapse-free survival (RFS), the rate of allogeneic stem cell transplantation (ASCT), and the minimal residual disease (MRD) negativity rate.
RESULTS: Fifty-nine patients (30 women and 29 men) with a median age of 35 years (range, 18-87 years) were treated. Overall, 46 patients (78%) responded, 35 of them (59%) achieving complete response. The overall MRD negativity rate among responders was 82%. Twenty-six patients (44%) received ASCT. Grade 3 to 4 toxic effects included prolonged thrombocytopenia (81%; n = 48), infections (73%; n = 43), and hyperbilirubinemia (14%; n = 8). Veno-occlusive disease (VOD) occurred in 9 patients (15%). With a median follow-up of 24 months, the median RFS and OS were 8 and 11 months, respectively. The 1-year RFS and OS rates were 40% and 46%, respectively. The 1-year OS rates for patients treated in salvage 1, salvage 2, and salvage 3 or beyond were 57%, 26%, and 39%, respectively (P = .03).
CONCLUSIONS AND RELEVANCE: The combination of inotuzumab with low-intensity mini-HCVD chemotherapy shows encouraging results in R/R ALL. The risk of VOD should be considered carefully in patients with previous liver damage and among transplant candidates.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01371630.
Предметные рубрики MeSH
AdolescentAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCyclophosphamideDacarbazineDexamethasoneDose-Response Relationship, DrugDoxorubicinDrug Resistance, NeoplasmFemaleHematopoietic Stem Cell TransplantationHumansInotuzumab OzogamicinMaleMiddle AgedPhiladelphia ChromosomePrecursor Cell Lymphoblastic Leukemia-LymphomaRecurrenceSalvage TherapySurvival AnalysisVincristineYoung Adult