10 research outputs found
Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study
Prolonging overall survival (OS) remains an unmet need in relapsed or refractory multiple myeloma (RRMM). In
ELOQUENT-2 (NCT01239797), elotuzumab plus lenalidomide/dexamethasone (ERd) significantly improved
progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd) in patients with RRMM and 1â3 prior lines of
therapy (LoTs). We report results from the pre-planned final OS analysis after a minimum follow-up of 70.6 months, the
longest reported for an antibody-based triplet in RRMM. Overall, 646 patients with RRMM and 1â3 prior LoTs were
randomized 1:1 to ERd or Rd. PFS and overall response rate were co-primary endpoints. OS was a key secondary
endpoint, with the final analysis planned after 427 deaths. ERd demonstrated a statistically significant 8.7-month
improvement in OS versus Rd (median, 48.3 vs 39.6 months; hazard ratio, 0.82 [95.4% Cl, 0.68â1.00]; P = 0.0408 [less
than allotted α of 0.046]), which was consistently observed across key predefined subgroups. No additional safety
signals with ERd at extended follow-up were reported. ERd is the first antibody-based triplet regimen shown to
significantly prolong OS in patients with RRMM and 1â3 prior LoTs. The magnitude of OS benefit was greatest among
patients with adverse prognostic factors, including older age, ISS stage III, IMWG high-risk disease, and 2â3 prior LoTs
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Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial.
BACKGROUND
Elotuzumab plus lenalidomide and dexamethasone has shown improved progression-free and overall survival versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. We aimed to assess these regimens in patients with newly diagnosed multiple myeloma who are ineligible for haematopoietic stem-cell transplantation (HSCT).
METHODS
ELOQUENT-1 is an open-label, multicentre, randomised, phase 3 trial conducted at 185 hospitals, oncology practices, and research centres in 19 countries. Eligible patients were aged 18 years or older with newly diagnosed, untreated, symptomatic myeloma and not candidates for high-dose therapy plus HSCT, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower. Patients were randomly assigned (1:1) to receive elotuzumab plus lenalidomide and dexamethasone or lenalidomide and dexamethasone using an interactive voice response system, stratified by the International Staging System (ISS; stage I-II vs III), age (<75 years vs â„75 years), and ECOG performance status (0 vs 1-2). Patients in the elotuzumab plus lenalidomide and dexamethasone group received elotuzumab administered intravenously at 10 mg/kg on days 1, 8, 15, and 22 during cycles 1 and 2, days 1 and 15 during cycles 3-18, and then at 20 mg/kg on day 1 for subsequent cycles. In both treatment groups, patients received 25 mg lenalidomide orally on days 1-21 of each cycle and 40 mg dexamethasone on days 1, 8, 15, and 22 of each cycle. The primary endpoint was progression-free survival, as per the primary definition from European Society for Blood and Marrow Transplantation criteria in all randomly assigned patients (intention-to-treat population). This study is registered with ClinicalTrials.gov, NCT01335399 (completed).
FINDINGS
Between Aug 4, 2011, and June 19, 2014, 748 patients were randomly assigned (374 in each treatment group) and 742 patients received treatment (333 (90%) of 371 in the elotuzumab plus lenalidomide and dexamethasone group vs 339 (91%) of 371 in the lenalidomide and dexamethasone group discontinued treatment). The median age of patients was 73·0 years (IQR 69·0-78·0), 294 (39%) patients were 75 years or older. Most patients were White (711 [95%]) and male (412 [55%]). At a minimum follow-up of 65·3 months, the median progression-free survival was not significantly different between the groups: 31·4 months (95% CI 26·2-36·8) in the elotuzumab plus lenalidomide and dexamethasone group versus 29·5 months (23·5-34·3) in the lenalidomide and dexamethasone group (HR 0·93, 95·71% CI 0·77-1·12; stratified log-rank p=0·44). The median follow-up was 70·6 months (IQR 35·1-79·2). The most common grade 3-4 treatment-related adverse event was neutropenia (64 [17%] of 371 vs 79 [21%] of 371). Study drug toxicity was the reported cause of death in five (1%) versus four (1%) patients.
INTERPRETATION
Elotuzumab plus lenalidomide and dexamethasone did not significantly improve progression-free survival versus lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for HSCT. Although these data contribute to the treatment landscape, further research is needed to find ways to improve treatments in the front-line setting.
FUNDING
Bristol Myers Squibb
Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study
Prolonging overall survival (OS) remains an unmet need in relapsed or refractory multiple myeloma (RRMM). In ELOQUENT-2 (NCT01239797), elotuzumab plus lenalidomide/dexamethasone (ERd) significantly improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd) in patients with RRMM and 1â3 prior lines of therapy (LoTs). We report results from the pre-planned final OS analysis after a minimum follow-up of 70.6 months, the longest reported for an antibody-based triplet in RRMM. Overall, 646 patients with RRMM and 1â3 prior LoTs were randomized 1:1 to ERd or Rd. PFS and overall response rate were co-primary endpoints. OS was a key secondary endpoint, with the final analysis planned after 427 deaths. ERd demonstrated a statistically significant 8.7-month improvement in OS versus Rd (median, 48.3 vs 39.6 months; hazard ratio, 0.82 [95.4% Cl, 0.68â1.00]; Pâ=â0.0408 [less than allotted α of 0.046]), which was consistently observed across key predefined subgroups. No additional safety signals with ERd at extended follow-up were reported. ERd is the first antibody-based triplet regimen shown to significantly prolong OS in patients with RRMM and 1â3 prior LoTs. The magnitude of OS benefit was greatest among patients with adverse prognostic factors, including older age, ISS stage III, IMWG high-risk disease, and 2â3 prior LoTs.This study was funded by Bristol-Myers Squibb Company in collaboration with AbbVie Biotherapeutics.Peer reviewe
Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study
Prolonging overall survival (OS) remains an unmet need in relapsed or refractory multiple myeloma (RRMM). In
ELOQUENT-2 (NCT01239797), elotuzumab plus lenalidomide/dexamethasone (ERd) significantly improved
progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd) in patients with RRMM and 1â3 prior lines of
therapy (LoTs). We report results from the pre-planned final OS analysis after a minimum follow-up of 70.6 months, the
longest reported for an antibody-based triplet in RRMM. Overall, 646 patients with RRMM and 1â3 prior LoTs were
randomized 1:1 to ERd or Rd. PFS and overall response rate were co-primary endpoints. OS was a key secondary
endpoint, with the final analysis planned after 427 deaths. ERd demonstrated a statistically significant 8.7-month
improvement in OS versus Rd (median, 48.3 vs 39.6 months; hazard ratio, 0.82 [95.4% Cl, 0.68â1.00]; P = 0.0408 [less
than allotted α of 0.046]), which was consistently observed across key predefined subgroups. No additional safety
signals with ERd at extended follow-up were reported. ERd is the first antibody-based triplet regimen shown to
significantly prolong OS in patients with RRMM and 1â3 prior LoTs. The magnitude of OS benefit was greatest among
patients with adverse prognostic factors, including older age, ISS stage III, IMWG high-risk disease, and 2â3 prior LoTs