Blinatumomab
Sources réglementaires consultées
Indications approuvées
- Leucémie aiguë lymphoblastique (LAL) à précurseurs B CD19+ en première ou deuxième rémission complète avec maladie résiduelle minimale ≥0,1 %, chez l’adulte et l’enfant à partir de 1 mois.
- LAL à précurseurs B CD19+ en rechute ou réfractaire, chez l’adulte et l’enfant à partir de 1 mois.
- LAL à précurseurs B CD19+, chromosome Philadelphie négatif, pendant la phase de consolidation d’une chimiothérapie multiphasique, chez l’adulte et l’enfant à partir de 1 mois.
Contre-indications
Absolues
- Hypersensibilité connue au blinatumomab ou à tout composant de la formulation.
Mises en garde cliniques
- Mise en garde encadrée · Il peut provoquer un syndrome de libération de cytokines potentiellement mortel ou fatal. Suspendre ou arrêter et traiter par corticostéroïdes selon la gravité. — DailyMed, BLINCYTO set_id 38b482a8-960b-4591-9857-5031ecb830aa
- Mise en garde encadrée · Il peut provoquer une toxicité neurologique sévère, potentiellement mortelle ou fatale, notamment un syndrome de neurotoxicité associé aux cellules effectrices immunitaires (ICANS). Surveiller et suspendre ou arrêter selon la gravité. Ne pas conduire ni utiliser de machines dangereuses pendant l’administration. — DailyMed, BLINCYTO set_id 38b482a8-960b-4591-9857-5031ecb830aa
- Mise en garde majeure · Éviter les vaccins vivants à partir d’au moins 2 semaines avant le traitement, pendant le traitement et jusqu’à récupération de la fonction immunitaire. — DailyMed, BLINCYTO set_id 38b482a8-960b-4591-9857-5031ecb830aa
- Mise en garde majeure · Surveiller les infections, le syndrome de lyse tumorale, la neutropénie et la neutropénie fébrile, l’élévation des enzymes hépatiques, la pancréatite, la leucoencéphalopathie et les erreurs de préparation ou d’administration. Adapter ou arrêter selon l’événement. — DailyMed, BLINCYTO set_id 38b482a8-960b-4591-9857-5031ecb830aa
Interactions médicamenteuses
- SévèreSubstrats du CYP450 à marge thérapeutique étroite
Mécanisme: La libération transitoire de cytokines peut supprimer les enzymes CYP450, surtout pendant les 9 premiers jours du cycle 1 et les 2 premiers jours du cycle 2.
Recommandation: Surveiller la toxicité, comme avec la warfarine, ou les concentrations, comme avec la ciclosporine, et ajuster le médicament concomitant si nécessaire.
DailyMed, BLINCYTO set_id 38b482a8-960b-4591-9857-5031ecb830aahttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=38b482a8-960b-4591-9857-5031ecb830aa
Effets indésirables
Communs (≥1%)
fièvre · réaction liée à la perfusion · céphalées · infection · douleur musculosquelettique · neutropénie · nausées · anémie · thrombopénie · diarrhée
Rares mais graves
syndrome de libération de cytokines fatal · syndrome de neurotoxicité associé aux cellules effectrices immunitaires (ICANS) ou toxicité neurologique fatale · sepsis · syndrome de lyse tumorale · pancréatite
Grossesse et allaitement
Il peut provoquer une toxicité fœtale et une lymphocytopénie B néonatale. Vérifier la grossesse avant le traitement ; utiliser une contraception pendant le traitement et pendant 48 heures après. Ne pas allaiter pendant le traitement ni pendant 48 heures après. Contrôler les lymphocytes B du nourrisson exposé in utero avant toute vaccination vivante.
Bibliographie récente (PubMed)
B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes. We conducted a phase 3 trial involving children with newly diagnosed standard-risk B-cell ALL who had an average or higher risk of relapse. Patients were randomly assigned to receive chemotherapy alone or chemotherapy plus two nonsequential 28-day cycles of blinatumomab. The primary end point was disease-free survival. The data and safety monitoring committee reviewed the results from the first interim efficacy analysis, which included 1440 patients who had undergone randomization (722 to chemotherapy alone and 718 to blinatumomab and chemotherapy) and recommended early termination of randomization. At a median follow-up of 2.5 years, the estimated 3-year disease-free survival (±SE) was 96.0±1.2% with blinatumomab and chemotherapy and 87.9±2.1% with chemotherapy alone (difference in restricted mean survival time, 72 days; 95% confidence interval, 36 to 108; P<0.001 by stratified log-rank test). The estimated 3-year disease-free survival among patients with an average relapse risk was 97.5±1.3% with blinatumomab and chemotherapy and 90.2±2.3% with chemotherapy alone; among those with a higher relapse risk, the corresponding values were 94.1±2.5% and 84.8±3.8%. Cytokine release syndrome, seizures, and sepsis of grade 3 or higher were rare during blinatumomab cycles, but the overall incidence of nonfatal sepsis and catheter-related infections was significantly higher among patients with an average relapse risk who had been assigned to receive blinatumomab and chemotherapy than among those assigned to receive chemotherap
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
Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission. In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with BCR::ABL1-negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.01% leukemic cells in bone marrow as assessed on flow cytometry) after induction and intensification chemotherapy to receive four cycles of blinatumomab in addition to four cycles of consolidation chemotherapy or to receive four cycles of consolidation chemotherapy alone. The primary end point was overall survival, and relapse-free survival was a secondary end point. The data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full count recovery was observed in 395 of 488 enrolled patients (81%). Of the 224 patients with MRD-negative status, 112 were assigned to each group. The characteristics of the patients were balanced between the groups. At a median follow-up of 43 months, an advantage was observed in the blinatumomab group as compared with the chemotherapy-only group with regard to overall survival (at 3 years: 85% vs. 68%; hazard ratio for death, 0.41; 95% confidence interval [CI], 0.23 to 0.73; P = 0.002), and the 3-year relapse-free survival was 80% with blinatumomab and 64% with chemotherapy alone (hazard ratio for relapse or death, 0.53; 95% CI, 0.32 to 0.87). A higher incidence of neuropsychiatric events was reported in the blinatumomab group than in the chemotherapy-only group. The addition of blinatumomab to consolidation chemotherapy in adult patients in
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
Ponatinib and blinatumomab are effective therapies in patients with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia, and their combination might be a promising treatment option. In this study, we aimed to evaluate this chemotherapy-free strategy. We did a single-centre, single-arm, phase 2 study at the University of Texas MD Anderson Cancer Center, Houston, TX, USA, in patients aged 18 years or older with newly diagnosed or relapsed or refractory Ph-positive acute lymphoblastic leukaemia or chronic myeloid leukaemia in lymphoid blast phase. Patients with an ECOG performance status of 2 or less who had a total bilirubin concentration two-times the upper limit of normal (ULN) or less (≤2·4 mg/dL), alanine aminotransferase and aspartate aminotransferase concentration no more than three-times the ULN, and serum lipase and amylase concentrations no more than three-times the ULN were eligible for inclusion. Ponatinib 30 mg orally and continuous intravenous blinatumomab 28 μg over 24 h (for 28 days each cycle) were given in combination for up to five 42-day cycles, followed by ponatinib monotherapy. Patients received 12 doses of intrathecal chemotherapy as CNS prophylaxis. The primary endpoints were complete molecular response (defined as absence of a detectable BCR-ABL1 transcript by PCR at a sensitivity of 0·01%) in patients with newly diagnosed disease and overall response in patients with relapsed or refractory disease or chronic myeloid leukaemia in lymphoid blast phase. All assessments were done according to the intention-to-treat principle. The trial completed its original target accrual and was amended on March 23, 2022, to enrol an additional 30 patients, thus increasing the sample size to 90 patients. The trial is registered with ClinicalTrials.gov, NCT03263572, and it is ongoing. Between Feb 6, 2018, to May 6, 2022, 60 (83%) of 72 patients assessed were enrolled and received ponatinib and blinatumomab (40 [67%] patients had newly dia