Once- versus twice-weekly carfilzomib in relapsed and refractory multiple myeloma by select patient characteristics: phase 3 A.R.R.O.W. study subgroup analysis

Meletios A Dimopoulos,Mei Huang,María-Victoria Mateos,Ruben Niesvizky,David S Siegel,Anita Zahlten-Kumeli,Michele Cavo,Katja Weisel,Roman Hajek,Philippe Moreau

doi:10.1038/s41408-020-0300-y

Abstract

The phase 3 A.R.R.O.W. study demonstrated that treatment with once-weekly carfilzomib (70 mg/m2) and dexamethasone (once-weekly Kd70 mg/m2) improved progression-free survival compared with twice-weekly carfilzomib (27 mg/m2) and dexamethasone (twice-weekly Kd27 mg/m2) in patients with relapsed and refractory multiple myeloma (RRMM; median, 11.2 versus 7.6 months; hazard ratio [HR] = 0.69; 95% confidence interval, 0.54–0.88; P = 0.0029). Once-weekly dosing also improved response rates and depth of response. We performed a subgroup analysis from A.R.R.O.W. according to age (<65, 65–74, or ≥75 years), renal function (creatinine clearance <50, ≥50–<80, or ≥80 mL/min), number of prior therapies (2 or 3), and bortezomib-refractory status (yes or no). Compared with twice-weekly Kd27 mg/m2, once-weekly Kd70 mg/m2 reduced the risk of progression or death (HR = 0.60–0.85) and increased overall response rates in nearly all the examined subgroups, consistent with reports in the overall A.R.R.O.W. population. The safety profiles of once-weekly Kd70 mg/m2 across subgroups were also generally consistent with those in the overall population. Findings from this subgroup analysis generally demonstrate a favorable benefit–risk profile of once-weekly Kd70 mg/m2, further supporting once-weekly carfilzomib dosing as an appropriate treatment option for patients with RRMM, regardless of baseline patient and disease characteristics.

Highlights

Multiple myeloma (MM) is the third most common hematologic malignancy worldwide, characterized by excessive proliferation of monoclonal plasma cells[1,2]
Oncology Group performance status (ECOG PS), International Staging System (ISS), renal impairment, exposure to multiple lines of therapy, refractoriness to treatment, and the presence of high-risk cytogenetics have been associated with poor prognosis and shorter survival in patients with MM6–10
The median PFS in patients aged

Summary

Introduction

Multiple myeloma (MM) is the third most common hematologic malignancy worldwide, characterized by excessive proliferation of monoclonal plasma cells[1,2]. MM remains incurable, with most patients relapsing and developing treatment-refractory disease[1]. Relapsed and refractory MM (RRMM) represents a challenging disease to treat, given the heterogeneity of the disease and patient population[3,4,5]. Oncology Group performance status (ECOG PS), International Staging System (ISS), renal impairment, exposure to multiple lines of therapy, refractoriness to treatment, and the presence of high-risk cytogenetics have been associated with poor prognosis and shorter survival in patients with MM (including RRMM)[6,7,8,9,10]. There is a continued need to identify safe and efficacious and convenient treatments across the heterogeneous RRMM patient population. For treatments with demonstrated safety and efficacy, convenience represents an important factor for optimizing adherence and patient quality of life[11,12,13]

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Discussion

Conclusion