Since carfilzomib was approved at a 27 mg/m2 twice-weekly dose, it has since been optimized at 56 mg/m2 twice-weekly and a recent study found benefits of a 70 mg/m2 once-weekly dose. However, most patients are still treated with the original approval dosage, suggesting they might be undertreated.
The majority of patients with relapsed/refractory multiple myeloma (RRMM) are being undertreated and are receiving carfilzomib (Kyprolis) at a lower dosage, according to research presented at the 60th American Society of Hematology Annual Meeting and Exposition.1
Since carfilzomib was approved in 2012 to treat RRMM, higher doses of the therapy have been studied. Since 2016, the dose has been optimized for patients to received 56 mg/m2 twice weekly (optimized dose-56 BIW) with dexamethasone, and the more recent A.R.R.O.W. study has shown that a once-weekly dose of 70 mg/m2 (70 QW) improves progression-free survival compared with the twice-weekly dose of 27 mg/m2 (27 BIW) that was approved.
Interim results of the phase 3 A.R.R.O.W. study were presented at the 2019 American Society of Clinical Oncology Annual Meeting and published in The Lancet Oncology.2
The authors used IQVIA’s Oncology Electronic Medical Records database to identify 1469 patients with MM who were diagnosed between January 1, 2010, and October 31, 2017, who received 3 or more doses of carfilzomib. They compared overall survival and time to next treatment (TTNT) among patients treated with 27 BIW with patients who received the optimized dose-56 BIW/70 QW.
Of the patients studied, 129 patients (8.8%) received either the optimized dose-56 BIW/70 QW and 1340 patients (91.2%) received 27 BIW. At 12 months, 90.3% of patients in the optimized dose-56 BIW/70 QW group were alive compared with 79.7% of patients in the 27 BIW group. Patients in the optimized dose-56 BIW/70 QW group also had a 64% lower risk of death than the 27 BIW group.
TTNT, which is a proxy for progression-free survival, was 17.5 months for the optimized dose-56 BIW/70 QW group, which was significantly longer than the 13.2 months for the 27 BIW group.
“Our findings suggest that these patient-relevant outcomes may be improved in a vast majority of RRMM patients currently under-treated with carfilzomib by optimizing the dose, taking into consideration patients’ comorbidities and ability to tolerate therapy,” the authors concluded.