68 research outputs found
Relative efficacy of treatment options in transplant-ineligible newly diagnosed multiple myeloma:results from a systematic literature review and network meta-analysis
Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR
Background: In the phase III CASTOR study in relapsed or refractory multiple myeloma, daratumumab, bortezomib, and dexamethasone (D-Vd) demonstrated significant clinical benefit versus Vd alone. Outcomes after 40.0 months of median follow-up are discussed. Patients and Methods: Eligible patients had received ≥ 1 line of treatment and were administered bortezomib (1.3 mg/m2) and dexamethasone (20 mg) for 8 cycles with or without daratumumab (16 mg/kg) until disease progression. Results: Of 498 patients in the intent-to-treat (ITT) population (D-Vd, n = 251; Vd, n = 247), 47% had 1 prior line of treatment (1PL; D-Vd, n = 122; Vd, n = 113). Median progression-free survival (PFS) was significantly prolonged with D-Vd versus Vd in the ITT population (16.7 vs. 7.1 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.25-0.40; P < .0001) and the 1PL subgroup (27.0 vs. 7.9 months; HR, 0.22; 95% CI, 0.15-0.32; P < .0001). In lenalidomide-refractory patients, the median PFS was 7.8 versus 4.9 months (HR, 0.44; 95% CI, 0.28-0.68; P = .0002) for D-Vd (n = 60) versus Vd (n = 81). Minimal residual disease (MRD)–negativity rates (10−5) were greater with D-Vd versus Vd (ITT: 14% vs. 2%; 1PL: 20% vs. 3%; both P < .0001). PFS2 was significantly prolonged with D-Vd versus Vd (ITT: HR, 0.48; 95% CI, 0.38-0.61; 1PL: HR, 0.35; 95% CI, 0.24-0.51; P < .0001). No new safety concerns were observed. Conclusion: After 3 years, D-Vd maintained significant benefits in patients with relapsed or refractory multiple myeloma with a consistent safety profile. D-Vd provided the greatest benefit at first relapse and increased MRD-negativity rates.CASTOR showed the significant clinical benefit of daratumumab plus bortezomib and dexamethasone for patients with previously treated multiple myeloma. With ∼3 years median follow-up, this regimen continues to demonstrate significantly improved progression-free survival with higher minimal residual dis
an interim analysis from the prospective GMMG-MM5 trial
We investigated the impact of subcutaneous versus intravenous bortezomib in
the MM5 trial of the German-Speaking Myeloma Multicenter Group which compared
bortezomib, doxorubicin, and dexamethasone with bortezomib, cyclophosphamide,
and dexamethasone induction therapy in newly diagnosed multiple myeloma. Based
on data from relapsed myeloma, the route of administration for bortezomib was
changed from intravenous to subcutaneous after 314 of 604 patients had been
enrolled. We analyzed 598 patients who received at least one dose of trial
medication. Adverse events were reported more frequently in patients treated
with intravenous bortezomib (intravenous=65%; subcutaneous=56%, P=0.02). Rates
of grade 2 or more peripheral neuropathy were higher in patients treated with
intravenous bortezomib during the third cycle (intravenous=8%;
subcutaneous=2%, P=0.001). Overall response rates were similar in patients
treated intravenously or subcutaneously. The presence of International Staging
System stage III disease, renal impairment or adverse cytogenetic
abnormalities did not have a negative impact on overall response rates in
either group. To our knowledge this is the largest study to present data
comparing subcutaneous with intravenous bortezomib in newly diagnosed myeloma.
We show better tolerance and similar overall response rates for subcutaneous
compared to intravenous bortezomib. The clinical trial is registered at
eudract.ema.europa.eu as n. 2010-019173-16
Phase 3 randomised study of daratumumab, bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): CASTOR
a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma
Background Despite novel therapeutic agents, most multiple myeloma (MM)
patients eventually relapse. Two large phase III trials have shown
significantly improved response rates (RR) of lenalidomide/dexamethasone
compared with placebo/dexamethasone in relapsed MM (RMM) patients. These
results have led to the approval of lenalidomide for RMM patients and
lenalidomide/dexamethasone has since become a widely accepted second-line
treatment. Furthermore, in RMM patients consolidation with high-dose
chemotherapy plus autologous stem cell transplantation has been shown to
significantly increase progression free survival (PFS) as compared to
cyclophosphamide in a phase III trial. The randomized prospective ReLApsE
trial is designed to evaluate PFS after lenalidomide/dexamethasone induction,
high-dose chemotherapy consolidation plus autologous stem cell transplantation
and lenalidomide maintenance compared with the well-established
lenalidomide/dexamethasone regimen in RMM patients. Methods/Design ReLApsE is
a randomized, open, multicenter phase III trial in a planned study population
of 282 RMM patients. All patients receive three lenalidomide/dexamethasone
cycles and - in absence of available stem cells from earlier harvesting -
undergo peripheral blood stem cell mobilization and harvesting. Subsequently,
patients in arm A continue on consecutive lenalidomide/dexamethasone cycles,
patients in arm B undergo high dose chemotherapy plus autologous stem cell
transplantation followed by lenalidomide maintenance until discontinuation
criteria are met. Therapeutic response is evaluated after the 3rd (arm A + B)
and the 5th lenalidomide/dexamethasone cycle (arm A) or 2 months after
autologous stem cell transplantation (arm B) and every 3 months thereafter
(arm A + B). After finishing the study treatment, patients are followed up for
survival and subsequent myeloma therapies. The expected trial duration is 6.25
years from first patient in to last patient out. The primary endpoint is PFS,
secondary endpoints include overall survival (OS), RR, time to best response
and the influence of early versus late salvage high dose chemotherapy plus
autologous stem cell transplantation on OS. Discussion This phase III trial is
designed to evaluate whether high dose chemotherapy plus autologous stem cell
transplantation and lenalidomide maintenance after lenalidomide/dexamethasone
induction improves PFS compared with the well-established continued
lenalidomide/dexamethasone regimen in RMM patients. Trial registration:
ISRCTN16345835 (date of registration 2010-08-24)
Early M-Protein Dynamics Predicts Progression-Free Survival in Patients With Relapsed/Refractory Multiple Myeloma
This study aimed to predict long-term progression-free survival (PFS) using early M-protein dynamic measurements in patients with relapsed/refractory multiple myeloma (MM). The PFS was modeled based on dynamic M-protein data from two phase III studies, POLLUX and CASTOR, which included 569 and 498 patients with relapsed/refractory MM, respectively. Both studies compared active controls (lenalidomide and dexamethasone, and bortezomib and dexamethasone, respectively) alone vs. in combination with daratumumab. Three M-protein dynamic features from the longitudinal M-protein data were evaluated up to different time cutoffs (1, 2, 3, and 6Â months). The abilities of early M-protein dynamic measurements to predict the PFS were evaluated using Cox proportional hazards survival models. Both univariate and multivariable analyses suggest that maximum reduction of M-protein (i.e., depth of response) was the most predictive of PFS. Despite the statistical significance, the baseline covariates provided very limited predictive value regarding the treatment effect of daratumumab. However, M-protein dynamic features obtained within the first 2Â months reasonably predicted PFS and the associated treatment effect of daratumumab. Specifically, the areas under the time-varying receiver operating characteristic curves for the model with the first 2Â months of M-protein dynamic data were ~Â 0.8 and 0.85 for POLLUX and CASTOR, respectively. Early M-protein data within the first 2Â months can provide a prospective and reasonable prediction of future long-term clinical benefit for patients with MM
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 1–3 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 1–3 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, 0.68–1.00]; 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 1–3 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 2–3 prior LoTs
Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network
During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events
Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma
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