brentuximab vedotin
Sources réglementaires consultées
Indications approuvées
- Lymphome de Hodgkin classique : stade III/IV non traité chez l’adulte avec AVD ; haut risque non traité à partir de 2 ans avec AVEPC ; consolidation adulte après auto-HSCT ; ou rechute après auto-HSCT ou au moins deux protocoles lorsque le patient n’est pas candidat à l’auto-HSCT.
- Chez l’adulte : lymphome anaplasique systémique à grandes cellules ou autres lymphomes T périphériques CD30+ non traités avec CHP ; sALCL après échec d’au moins un protocole ; pcALCL ou mycosis fongoïde CD30+ après traitement systémique ; et LBCL en rechute/réfractaire après au moins deux lignes, non éligible à l’auto-HSCT ou aux CAR-T, avec lénalidomide et rituximab.
Contre-indications
Absolues
- Utilisation concomitante avec la bléomycine en raison de la toxicité pulmonaire.
Mises en garde cliniques
- Mise en garde encadrée · L’infection par le virus JC peut provoquer une leucoencéphalopathie multifocale progressive et le décès. Arrêter définitivement si une LEMP est confirmée. — DailyMed, ADCETRIS set_id 3904f8dd-1aef-3490-e48f-bd55f32ed67f
- Mise en garde majeure · Surveiller la neuropathie cumulative, les cytopénies et la neutropénie fébrile, les infections opportunistes, le syndrome de lyse tumorale, l’hépatotoxicité, la toxicité pulmonaire, le SJS/TEN, les complications gastro-intestinales graves et l’hyperglycémie ; adapter ou arrêter selon l’événement. — DailyMed, ADCETRIS set_id 3904f8dd-1aef-3490-e48f-bd55f32ed67f
- Mise en garde majeure · Interrompre la perfusion en cas de réaction et arrêter immédiatement en cas d’anaphylaxie. — DailyMed, ADCETRIS set_id 3904f8dd-1aef-3490-e48f-bd55f32ed67f
Interactions médicamenteuses
- ModéréeInhibiteurs puissants du CYP3A4
Mécanisme: Ils peuvent augmenter l’exposition au MMAE et la toxicité du brentuximab védotine.
Recommandation: Surveiller étroitement les effets indésirables si l’association est nécessaire.
DailyMed, ADCETRIS set_id 3904f8dd-1aef-3490-e48f-bd55f32ed67fhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3904f8dd-1aef-3490-e48f-bd55f32ed67f
Effets indésirables
Communs (≥1%)
neuropathie périphérique · nausées · fatigue · douleur musculosquelettique · constipation · diarrhée · vomissements · fièvre · infection des voies respiratoires supérieures · éruption cutanée · mucite · douleur abdominale
Rares mais graves
leucoencéphalopathie multifocale progressive mortelle · anaphylaxie · neutropénie fébrile · infection opportuniste grave · syndrome de Stevens-Johnson ou nécrolyse épidermique toxique
Grossesse et allaitement
Il peut provoquer une toxicité fœtale. Vérifier la grossesse avant le traitement. Les femmes doivent utiliser une contraception pendant le traitement et pendant 2 mois après ; les hommes ayant une partenaire en âge de procréer doivent utiliser une contraception pendant le traitement et pendant 4 mois après. L’allaitement n’est pas recommandé pendant le traitement.
Bibliographie récente (PubMed)
Incorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin's lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin's lymphoma, including in preliminary studies involving previously untreated patients. We conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin's lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause. Of 994 patients who underwent randomization, 970 were included in the intention-to-treat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P = 0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse even
Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8570 new patients annually and representing ~10% of all lymphomas in the United States. HL is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL (also called nodular lymphocyte predominant B-cell lymphoma). Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography (PET) scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early-stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, whereas those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. However, newer agents including brentuximab vedotin and anti-PD-1 antibodies are now standardly incorporated into frontline therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, non-myeloablative allogeneic transplant or participation in a clinical trial should be considered.
For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripher
On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.
In patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), brentuximab vedotin (BV) as monotherapy or combined with either lenalidomide (Len) or rituximab (R) has demonstrated efficacy with acceptable safety. We evaluated the efficacy and safety of BV + Len + R versus placebo + Len + R in patients with R/R DLBCL. ECHELON-3 is a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial comparing BV + Len + R with placebo + Len + R in patients with R/R DLBCL. Patients received BV or placebo once every 3 weeks, Len once daily, and R once every 3 weeks. The primary end point was overall survival (OS), and secondary end points included investigator-assessed progression-free survival (PFS) and objective response rate (ORR). A prespecified interim analysis was performed after 134 OS events, with two-sided P = .0232 as the efficacy boundary. Patients (N = 230) were randomly assigned to receive BV + Len + R (n = 112) or placebo + Len + R (n = 118). Two patients in the placebo arm did not receive treatment. With a median follow-up of 16.4 months, the median OS was 13.8 months with BV + Len + R versus 8.5 months with placebo + Len + R (hazard ratio, 0.63 [95% CI, 0.45 to 0.89]; two-sided P = .009). The median PFS was 4.2 months with BV + Len + R versus 2.6 months with placebo + Len + R (hazard ratio, 0.53 [95% CI, 0.38 to 0.73]; two-sided P < .001). The ORR was 64% ([95% CI, 55 to 73]; two-sided P < .001) with BV + Len + R and 42% (95% CI, 33 to 51) with placebo + Len + R; complete response rates were 40% and 19%, respectively. Treatment-emergent adverse events (AEs) occurred in 97% of patients in both arms. In both arms, the most common treatment-emergent AEs were neutropenia, thrombocytopenia, diarrhea, and anemia. BV + Len + R demonstrated a statistically significant survival benefit with a manageable safety profile in heavily pretreated patients with R/R DLBCL.