Elotuzumab
Sources réglementaires consultées
Indications approuvées
- Myélome multiple de l’adulte, avec lénalidomide et dexaméthasone, après un à trois traitements antérieurs.
- Myélome multiple de l’adulte, avec pomalidomide et dexaméthasone, après au moins deux traitements antérieurs comprenant lénalidomide et un inhibiteur du protéasome.
Mises en garde cliniques
- Mise en garde majeure · Il peut provoquer des réactions graves à la perfusion. Prémédiquer et surveiller pendant et après l’administration. — DailyMed, EMPLICITI set_id 80686b7e-f6f4-4154-b5c0-c846425e2d91
- Mise en garde majeure · Surveiller les infections graves ou opportunistes, les seconds cancers primitifs et l’hépatotoxicité ; interrompre et évaluer toute atteinte hépatique importante. — DailyMed, EMPLICITI set_id 80686b7e-f6f4-4154-b5c0-c846425e2d91
- Il peut interférer avec l’électrophorèse et l’immunofixation sériques et produire une fausse élévation du composant monoclonal, affectant l’évaluation de la réponse complète. — DailyMed, EMPLICITI set_id 80686b7e-f6f4-4154-b5c0-c846425e2d91
Interactions médicamenteuses
- SévèreLénalidomide, pomalidomide et dexaméthasone
Mécanisme: Les médicaments associés ont leurs propres interactions qui déterminent la sécurité du protocole combiné.
Recommandation: Consulter et appliquer les interactions et contre-indications de chaque médicament associé avant et pendant le traitement combiné.
DailyMed, EMPLICITI set_id 80686b7e-f6f4-4154-b5c0-c846425e2d91https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=80686b7e-f6f4-4154-b5c0-c846425e2d91
Effets indésirables
Communs (≥1%)
fatigue · diarrhée · fièvre · constipation · toux · neuropathie périphérique · rhinopharyngite ou infection des voies respiratoires supérieures · diminution de l’appétit · pneumonie · hyperglycémie avec pomalidomide
Rares mais graves
réaction grave à la perfusion · infection grave ou opportuniste · hépatotoxicité · second cancer primitif
Grossesse et allaitement
Il n’existe pas de données adéquates pour l’elotuzumab seul. Les associations avec lénalidomide ou pomalidomide peuvent provoquer une toxicité embryo-fœtale et sont contre-indiquées pendant la grossesse ; respecter leurs programmes de prévention. Ne pas allaiter pendant le traitement.
Bibliographie récente (PubMed)
In the phase II ELOQUENT-3 trial (ClinicalTrials.gov identifier: NCT02654132), elotuzumab combined with pomalidomide/dexamethasone (EPd) significantly improved progression-free survival (PFS) versus pomalidomide/dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (RRMM) previously treated with lenalidomide and a proteasome inhibitor (PI). Here, we present the final overall survival (OS) results. Patients with RRMM who had received ≥ 2 prior lines of therapy, with disease refractory to last therapy and either refractory or relapsed and refractory to lenalidomide and a PI were randomly assigned (1:1) to receive EPd or Pd. The primary end point was PFS per investigator assessment. ORR and OS were secondary end points planned to be tested hierarchically. A total of 117 patients were randomly assigned to EPd (n = 60) and Pd (n = 57). Among treated patients (EPd 60, Pd 55), there were 37 (61.7%) deaths in the EPd group and 41 (74.5%) in the Pd group, most commonly because of disease progression (EPd 41.7%, Pd 49.1%). Median (95% CI) OS was significantly improved with EPd (29.8 [22.9 to 45.7] months) versus Pd (17.4 [13.8 to 27.7] months), with a hazard ratio of 0.59 (95% CI, 0.37 to 0.93; P = .0217). OS benefit with EPd was observed in most patient subgroups. The safety profile of EPd was consistent with prior reports with no new safety signals detected. EPd demonstrated a statistically significant improvement in OS versus Pd in patients with RRMM previously treated with lenalidomide and a PI who had disease refractory to last therapy. In this setting, ELOQUENT-3 is the first randomized study of a triplet regimen incorporating a monoclonal antibody and Pd to improve both PFS and OS significantly.
Multiple myeloma is a malignant hematological tumor characterized by the proliferation of clonal plasma cells in the bone marrow causing organ damage. Despite improved survival rates due to the increasing availability of therapeutic options in recent decades, it remains an incurable disease, with most patients ultimately relapsing. Consequently, relapsed/refractory multiple myeloma disease (RRMM) has become a treatment priority. Immunotherapy is the backbone of treatment in RRMM, starting with monoclonal antibodies such as elotuzumab, daratumumab, and isatuximab. The aim of this review is summarizing the results of RRMM trials with monoclonal antibodies and of the principal ongoing trials containing them. Additionally, we put a brief focus on novel drugs (such as bispecific antibodies) to provide a better overview. The advent of monoclonal antibodies has been nothing short of a game-changer for multi-refractory patients. It has opened up a whole new world of possibilities, offering myeloma patients a brighter and more hopeful future, even in the face of relapse.
Light-chain amyloidosis is a rare disorder where a small clone of plasma cells is producing excess toxic light chains that deposit in various organs and cause dysfunction. Cardiac involvement is a major determinant of survival and rapid reduction of light chain is critical for recovery of organ function and overall survival. Immunotherapy targeting the clonal plasma cells and amyloid fibrils has emerged as a promising candidate. Daratumumab, both alone and in combinations with other anti-myeloma agents, is able to achieve deep hematologic responses and has greatly improved outcomes. Isatuximab, elotuzumab, and CAEL101 have also shown promising results and further studies are ongoing in the frontline as well as the relapsed/refractory setting. The frailty of AL patients and the relapsing/remitting nature of the disease present unique challenges, and the low toxicity of monoclonal antibodies makes them well-suited for these patients. Other immunotherapy agents including chimeric antigen receptor T cells, bispecific antibodies, and antibody-drug conjugates have altered the landscape in treatment of multiple myeloma, and are in the early phase of evaluation in patients with AL amyloidosis with results eagerly awaited.