Abstract
BackgroundIn ASPIRE, carfilzomib, lenalidomide, and dexamethasone (KRd) significantly improved progression-free survival (PFS) and response rates versus lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma. Per protocol, patients received KRd for a maximum of 18 cycles followed by Rd to progression, so the benefit/risk profile of KRd to progression was not established.MethodsThis post hoc analysis evaluated the efficacy and safety of KRd versus Rd at 18 months from randomization. Cumulative rates of complete response (CR) or better over time and PFS hazard ratio (HR) at 18 months were evaluated for KRd versus Rd. PFS HRs were also assessed according to cytogenetic risk, prior lines of therapy, and prior bortezomib treatment. Cox regression analysis was used to evaluate PFS HRs.ResultsThe hazard ratio (HR) for PFS at 18 months was 0.58 versus 0.69 for the overall ASPIRE study. Patients with high-risk cytogenetics, ≥ 1 prior lines of therapy, and prior bortezomib exposure benefited from KRd up to 18 months versus Rd. The HRs for PFS at 18 months in the pre-defined subgroups were lower than those in the overall study. The difference in the proportion of KRd and Rd patients achieving at least a complete response (CR) increased dramatically over the first 18 months and then remained relatively constant. The safety profile at 18 months was consistent with previous findings.ConclusionsThe improved PFS HR at 18 months and the continued increase in CR rates for KRd through 18 cycles suggest that there may be a benefit of continued carfilzomib treatment.Trial registrationClinical trials.gov NCT01080391. Registered 2 March 2010.
Highlights
In ASPIRE, carfilzomib, lenalidomide, and dexamethasone (KRd) significantly improved progressionfree survival (PFS) and response rates versus lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma
PFS hazard ratio (HR) at 18 months favored KRd versus Lenalidomide and dexamethasone (Rd) in patients with high-risk cytogenetics (HR 0.56; 95% CI 0.31–0.99), standard cytogenetic risk (HR 0.54; 95% CI 0.37–0.80), one prior line of treatment (HR 0.58; 95% CI 0.41– 0.82), two or more prior lines of treatment (HR 0.60; 95% CI 0.45–0.81), and prior bortezomib exposure (HR 0.59; 95% CI 0.45–0.78) (Table 1)
Previously reported results from the phase III ASPIRE study showed that the addition of carfilzomib to Rd resulted in high ≥ complete response (CR) rates and a clinically meaningful and statistically significant improvement in PFS and overall survival (OS) in patients with relapsed MM who had received at least one to three prior lines of therapy [25, 29]
Summary
In ASPIRE, carfilzomib, lenalidomide, and dexamethasone (KRd) significantly improved progressionfree survival (PFS) and response rates versus lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma. Recent advances in the treatment of MM have led to improvements in depth of response, progression-free survival (PFS), and overall survival (OS) in patients with MM [11,12,13]. Despite improvements in clinical outcome, almost all patients with MM eventually relapse. Based on positive clinical study results showing improvements in PFS and OS, there has been a shift to administer continuous therapy for both transplant-eligible and transplant-ineligible MM patients in place of a fixed-dose treatment [14,15,16,17,18,19,20]. The rationale for continuous therapy is to control minimal residual disease in order to delay disease recurrence [21]
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