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S. Bringhen et al.
561 study (once-weekly carfilzomib) and 58 from the IST-CAR-506 study (twice-weekly carfilzomib). Patients' characteristics are listed in Table 1. The median age at diagnosis in the entire population was 72 years (range, 55- 86 years). Cytogenetic data were available in 94 patients: 37 (31%) had high-risk chromosomal abnormalities by FISH, including 10% of patients with t(4;14), 3% with t(14;16), and 18% with del(17p), while 57 patients (47%) were classified as standard-risk. No significant differences were observed in the two groups between the percentage of patients with ISS 3 disease (32% vs. 40%; P=0.45), high-risk FISH (30% vs. 31%; P=0.40) or Frailty Score (6% vs. 17%; P=0.09). The median follow up of the entire cohort was 39 months [interquartile range (IQR): 31-47], without any difference between the two groups.
Overall, 119 of 121 patients enrolled in the studies start- ed induction therapy (Figure 1): 63 in the once-weekly group and 56 in the twice-weekly group. Two patients did not start therapy in the twice-weekly group: one with- drew consent and one was lost to follow up. Ninety patients entered the maintenance phase: 47 (75%) and 43 (74%) in the once- and twice-weekly groups, respectively (Figure 1).
In the ITT population, the median PFS from enrollment was 35.7 months (95%CI: 23.7-NR) in the once-weekly group and 35.5 months (95%CI: 24.3-NR) in the twice-
weekly group, with, respectively, 47% and 49% of patients alive and free from progression at three years (Figure 2A). When adjusting for age, ISS, FISH, and Frailty Score, no significant differences in the risk of progression or death were observed between the once-weekly and the twice-weekly carfilzomib groups (HR: 1.39; P=0.26). Median PFS-2 was similar in patients receiving once- weekly (48.6 months; 95%CI: 36.5-NR) and twice-weekly (48.5 months; 95%CI: 44.1-NR) carfilzomib (HR: 1.25; P=0.51) (Figure 2B). At three years, median OS was not reached in either group, with 70% and 72% of patients alive in the two groups, respectively (Figure 2C). No dif- ference in the risk of death was observed between the once-weekly and the twice-weekly carfilzomib groups when adjusting for age, ISS, FISH and Frailty Score (HR: 1.27; P=0.50). We also assessed PFS and OS according to cytogenetic risk. No significant difference in 3-year PFS (52% vs. 43%; HR: 0.76; P=0.38) and 3-year OS (78% vs. 73%; HR: 0.71; P=0.36) was reported between standard- and high-risk FISH patients, with a greater reduction in the risk of progression or death in the once-weekly (HR: 1.17; P=0.72) than in the twice-weekly carfilzomib group (HR: 0.52; P=0.12; interaction P=0.19).
The median duration of maintenance was 17 months (IQR: 4-28) in the once-weekly and 20 months (IQR 7-32) in the twice-weekly group (P=0.17). At three years, PFS_m
AB
C
Figure 2. Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma. (A) Intention-to-treat progression-free survival (ITT PFS). (B) Intention-to-treat progression-free survival 2 (ITT PFS-2). (C) Intention-to-treat overall survival (ITT OS). (Note that PFS-2 was calculated from the date of enrollment to the date of second relapse/progression or death or the date the patient was last known to be in remission.)
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haematologica | 2019; 104(8)