FORTE Trial of Carfilzomib-Containing Induction, Consolidation, and Maintenance in Newly Diagnosed Multiple Myeloma: Subgroup Analysis by Cytogenetic Risk

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In a prespecified analysis of the Italian phase II FORTE trial reported in The Lancet Oncology, Mina et al identified outcomes associated with the number of high-risk cytogenetic abnormalities (HRCAs) across treatment groups receiving carfilzomib-containing induction, consolidation, and maintenance regimens or comparator treatment for newly diagnosed multiple myeloma.

The FORTE trial showed that lenalidomide/dexamethasone plus carfilzomib (KRd) induction resulted in a higher proportion of patients with a very good partial response or better vs carfilzomib, cyclophosphamide, and dexamethasone (KCd) and that carfilzomib/lenalidomide maintenance prolonged progression-free survival vs lenalidomide maintenance.

Study Details

In the open-label multicenter trial, 477 patients were randomly assigned 1:1:1 between February 2015 and April 2017 to receive four 28-day lenalidomide/dexamethasone plus carfilzomib (KRd) induction cycles, melphalan and autologous stem-cell transplantation (ASCT), and four 28-day KRd consolidation cycles; twelve 28-day KRd cycles; or four 28-day KCd induction cycles, melphalan, and ASCT, and four 28-day KCd consolidation cycles. After consolidation,  patients were stratified according to induction-consolidation and randomly assigned to maintenance with carfilzomib/lenalidomide or lenalidomide alone.

The current analysis included 396 patients with complete data on the HRCAs del(17p), t(4;14), t(14;16), del(1p), gain(1q), and amp(1q). Outcomes were assessed across all treatment groups according to the number of HRCAs.

Key Findings

Median follow-up from first randomization was 51 months (interquartile range [IQR] = 46–56 months). Rates of 1-year sustained minimal residual disease negativity were 35% (53/153) among patients with no HRCAs, 41% (57/138) among those with one HRCA, and 24% (25/105) among those with two or more HRCAs.

Four-year progression-free survival from first randomization was 71% (95% confidence interval [CI] = 64%–78%) in patients with no HRCAs, 60% (95% CI = 52%–69%) in those with one HRCA (hazard ratio [HR] vs 0 HRCAs = 1.33, P = .15), and 39% (95% CI = 30%–50%) in those with two or more HRCAs (HR vs 0 HRCAs =  2.56, P < .0001; HR vs 1 HRCA =1.92, P = .0004).

Four-year overall survival from first randomization was 94% (95% CI = 91%–98%) in patients with no HRCAs, 83% (95% CI = 76%–90%) in those with one HRCA (HR vs 0 HRCAs = 2.55,  P = .013), and 63% (95% CI = 54%–4%) in those with two or more HRCAs (HR vs 0 HRCAs = 6.53, P < .0001); HR vs 1 HRCA = 2.56, P = .0004). 

Median duration of follow-up from second randomization was 37 months (IQR = 33–42 months). Three-year progression-free survival from second randomization was 80% (95% CI = 74%–88%) in patients with no HRCAs, 68% (95% CI = 59%–78%) in those with one HRCA (HR vs 0 HRCAs = 1.68, P = .048), and 53% (95% CI = 42%-67%) in those with two or more HRCAs (HR vs 0 HRCAs = 2.74, P = .0003); HR vs 1 HRCA = 1.63, P = .051).

The investigators concluded: “This preplanned analysis of the FORTE trial showed that carfilzomib-based induction–intensification–consolidation regimens are effective strategies in patients with standard risk (zero HRCA) and high-risk (one HRCA) myeloma, resulting in similar rates of progression-free survival and 1-year sustained minimal residual disease negativity. Despite promising progression-free survival, patients with ultra-high-risk disease (those with two or more HRCAs) still have an increased risk of progression and death and therefore represent an unmet medical need.”

Francesca Gay, MD, PhD, Division of Hematology, University of Torino, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Amgen and Celgene/Bristol Myers Squibb. For full disclosures of the study authors, visit

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