Elotuzumab
Regulatory sources consulted
Approved indications
- Adult multiple myeloma, with lenalidomide and dexamethasone, after one to three prior therapies.
- Adult multiple myeloma, with pomalidomide and dexamethasone, after at least two prior therapies including lenalidomide and a proteasome inhibitor.
Clinical warnings
- Major warning · It can cause serious infusion reactions. Premedicate and monitor during and after administration. — DailyMed, EMPLICITI set_id 80686b7e-f6f4-4154-b5c0-c846425e2d91
- Major warning · Monitor for serious or opportunistic infections, second primary malignancies, and hepatotoxicity; interrupt and evaluate clinically significant liver injury. — DailyMed, EMPLICITI set_id 80686b7e-f6f4-4154-b5c0-c846425e2d91
- It can interfere with serum protein electrophoresis and immunofixation and cause a false monoclonal-component elevation, affecting complete-response assessment. — DailyMed, EMPLICITI set_id 80686b7e-f6f4-4154-b5c0-c846425e2d91
Drug interactions
- HighLenalidomide, pomalidomide, and dexamethasone
Mechanism: The companion medicines have their own interactions that determine combination-regimen safety.
Recommendation: Consult and apply each companion medicine’s interactions and contraindications before and during combination treatment.
DailyMed, EMPLICITI set_id 80686b7e-f6f4-4154-b5c0-c846425e2d91https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=80686b7e-f6f4-4154-b5c0-c846425e2d91
Adverse events
Common (≥1%)
fatigue · diarrhea · pyrexia · constipation · cough · peripheral neuropathy · nasopharyngitis or upper respiratory tract infection · decreased appetite · pneumonia · hyperglycemia with pomalidomide
Rare but serious
serious infusion reaction · serious or opportunistic infection · hepatotoxicity · second primary malignancy
Pregnancy and lactation
There are no adequate data for elotuzumab alone. Combinations with lenalidomide or pomalidomide can cause embryo-fetal harm and are contraindicated in pregnancy; follow their pregnancy-prevention programs. Do not breastfeed during treatment.
Recent literature (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.