Inotuzumab ozogamicin
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Leucemia linfoblástica aguda de precursores B CD22+ recidivante o refractaria en adultos y pacientes pediátricos desde 1 año.
Advertencias clínicas
- Advertencia destacada (boxed warning) · Puede causar hepatotoxicidad, incluida enfermedad venooclusiva o síndrome de obstrucción sinusoidal mortal, y aumenta la mortalidad no relacionada con recaída después del trasplante hematopoyético. Suspende definitivamente ante enfermedad venooclusiva, síndrome de obstrucción sinusoidal u otra hepatotoxicidad grave. — DailyMed, BESPONSA set_id cc7014b1-c775-411d-b374-8113248b4077
- Advertencia mayor · Vigila mielosupresión, infecciones, hemorragia, reacciones a la perfusión y prolongación del QT. Interrumpe la perfusión y trata la reacción; suspende definitivamente ante una reacción grave o potencialmente mortal. — DailyMed, BESPONSA set_id cc7014b1-c775-411d-b374-8113248b4077
Interacciones medicamentosas
- SeveraFármacos que prolongan el QT
Mecanismo: El efecto aditivo puede aumentar la prolongación clínicamente significativa del QTc y el riesgo de torsades de pointes.
Recomendación: Evita o sustituye cuando sea posible. Si la combinación es inevitable, controla ECG y electrolitos antes, después del inicio y periódicamente.
DailyMed, BESPONSA set_id cc7014b1-c775-411d-b374-8113248b4077https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cc7014b1-c775-411d-b374-8113248b4077
Eventos adversos
Comunes (≥1%)
trombocitopenia · neutropenia o fiebre neutropénica · infección · anemia · hemorragia · náuseas o vómitos · fatiga · elevación de transaminasas, GGT o bilirrubina · dolor abdominal
Raros pero graves
enfermedad venooclusiva o síndrome de obstrucción sinusoidal mortal · mielosupresión grave · hemorragia grave · prolongación clínicamente significativa del QT
Embarazo y lactancia
Puede causar daño fetal. Verifica el embarazo antes de iniciar; usa anticoncepción durante el tratamiento y durante 8 meses después en mujeres y 5 meses después en hombres con pareja con capacidad reproductiva. No amamantes durante el tratamiento ni durante 2 meses después.
Bibliografía reciente (PubMed)
Acute lymphoblastic leukemia (ALL) is a disease of lymphoid progenitor cells arising in the bone marrow and extramedullary sites. While it is the most common pediatric cancer, ALL is a rare disease overall, with approximately 6500 new cases diagnosed in the United States, in 2024. Current treatment relies on multiagent chemotherapy administered over 2-3 years, resulting in long-term survival in 80%-90% in pediatric patients compared to 40%-50% in adult patients, depending upon patient- and disease-specific characteristics. Historically considered a poor risk ALL subtype, the treatment and outcome of Philadelphia chromosome (Ph)-positive B-cell ALL were drastically changed with the advent of the BCR::ABL1 tyrosine kinase inhibitors (TKIs). The combination of a TKI with a backbone of multiagent chemotherapy, or more recently blinatumomab, is the mainstay of therapy, resulting in 5-year survival rates of 80+%. Achieving a complete molecular remission, particularly by next generation sequencing, is an important prognostic indicator, which may identify patients who may avoid allogeneic stem cell transplantation (SCT). The treatment approach for patients with Ph-negative B-cell ALL was historically composed of a chemotherapy backbone (either pediatric-inspired, or Hyper-CVAD based). Novel agents including inotuzumab ozogamicin and blinatumomab are being incorporated into these regimens to improve the rates of measurable residual disease negativity and long-term outcomes. While differences in long-term survival rates differ between age groups, such as adolescents and young adults compared to older adults (≥ 60 years), with these immunotherapy-chemotherapy regimens, the 4-year survival rates have improved to 80%-85% among patients who are able to receive these treatments. Elderly patients represent a difficult population to treat due to poor chemotherapy tolerance, high-risk disease features, and increased risk of developing therapy-related myeloid neoplasms. The use of ino
The outcome of older patients with B-cell acute lymphocytic leukaemia is inferior to that in younger patients due to the adverse disease biology and their inability to tolerate intensive therapy. We aimed to study the long-term outcomes of inotuzumab ozogamicin with or without blinatumomab in combination with low-intensity chemotherapy in these patients. For this open-label phase 2 trial, patients aged 60 years or older with newly diagnosed, Philadelphia-chromosome negative, B-cell acute lymphocytic leukaemia, and an ECOG performance status of 3 or lower were eligible. This study was conducted at the University of Texas MD Anderson Cancer Center. The induction chemotherapy consisted of mini-hyper-CVD and has been published before; inotuzumab ozogamicin was administered intravenously on day 3 of the first four cycles at a dose of 1·3-1·8 mg/m2 in cycle 1, followed by 1·0-1·3 mg/m2 in subsequent cycles (cycles 2-4). Maintenance therapy with dose-reduced POMP (6-mercaptopurine, vincristine, methotrexate, and prednisone) was given for 3 years. From patient 50 onwards, the study protocol was amended to fractionate inotuzumab ozogamicin to a maximum cumulative dose of 2·7 mg/m2 (0·9 mg/m2 during cycle 1 fractionated into 0·6 mg/m2 on day 2 and 0·3 mg/m2 on day 8 of cycle 1, and 0·6 mg/m2 in cycles 2-4 fractionated into 0·3 mg/m2 on day 2 and 0·3 mg/m2 on day 8) followed by blinatumomab for four cycles (cycles 5-8). POMP maintenance was shortened to 12 cycles with one cycle of blinatumomab administered by continuous infusion after every three cycles of POMP. The primary endpoint was progression-free survival and was analysed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT01371630) and the present data is from the newly diagnosed, older subgroup of patients treated on the phase 2 portion of this trial; the trial is still enrolling patients. Between Nov 11, 2011, and March 31, 2022, 80 patients were enrolled and treated (32 female and 48
Preclinical studies suggest that Bcl-2 inhibition with venetoclax has antileukemic activity in acute lymphoblastic leukemia (ALL) and may synergize with conventional chemotherapy. We designed a phase 1/2 clinical trial to evaluate the safety and efficacy of low-intensity chemotherapy in combination with venetoclax in adults with relapsed or refractory ALL. Patients received the mini-hyper-CVD regimen (dose-attenuated hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate and cytarabine) in combination with venetoclax (200 mg or 400 mg daily) on days 1 to 14 in cycle 1 and on days 1 to 7 in consolidation cycles. Twenty-two patients were treated. The median number of prior therapies was 2 (range, 1-6). Thirteen patients (59%) had undergone prior allogeneic stem cell transplant (allo-SCT), and 7 of 18 patients (39%) with B-cell ALL had previously received both inotuzumab ozogamicin and blinatumomab. The recommended phase 2 dose of venetoclax in the combination regimen was 400 mg daily. The composite complete remission (CR) and CR with incomplete hematologic recovery (CRi) rate was 57% (CR, 43%; CRi, 14%), and 45% of responders achieved measurable residual disease negativity by multiparameter flow cytometry. Four patients proceeded to allo-SCT. The median duration of response was 6.3 months. The median overall survival was 7.1 months, and the 1-year overall survival rate was 29%. The most common grade ≥3 nonhematologic adverse events were infection in 17 patients (77%) and febrile neutropenia in 4 patients (18%). Overall, the combination of mini-hyper-CVD plus venetoclax was active in heavily pretreated relapsed/refractory ALL. Further development of venetoclax-based combinations in ALL is warranted. This trial is registered at www.clinicaltrials.gov as #NCT03808610.