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M.-V. Mateos et al.
Figure 1. Disposition of patients aged 65 to 74 years and ≥75 years based on the intent-to-treat population of (A) POLLUX and (B) CASTOR. D-Rd: daratumumab/lenalidomide/dexamethasone; Rd: lenalidomide/dexamethasone; D-Vd: daratumumab/bortezomib/dexamethasone; Vd, bortezomib/dexametha- sone. aBased on reason ‘patient refused to further study treatment’. bAll patients were to receive eight cycles of bortezomib and dexamethasone. After cycle 8, patients receiving only bortezomib and dexamethasone were entered into an observation phase, while patients in the daratumumab group continued to receive dara- tumumab monotherapy every 4 weeks. All patients had discontinued or completed eight cycles of bortezomib and dexamethasone by the interim analysis.15
or better (75.9% versus 41.2%; P=0.0059) and CR or better (55.2% versus 8.8%; P<0.0001), respectively (Table 2). Similar findings were observed in patients aged 65 to 74 years (ORR: 92.6% versus 80.2%; P=0.0057; VGPR or bet- ter: 76.2% versus 49.1%; P<0.0001; CR or better: 50.0% versus 22.6%; P<0.0001). In both age groups, deeper responses with D-Rd versus Rd translated to a significantly higher proportion of patients with minimal residual dis- ease (MRD)-negative status at a sensitivity threshold of 10–5 (Table 2). Among patients aged ≥75 years, the rates of MRD negativity were 27.6% versus 5.7% (P=0.014464), and in patients aged 65 to 74, the rates were 23.4% versus 8.3% (P=0.001520).
In patients who received one prior line of therapy, a higher proportion of patients who received D-Rd achieved MRD negativity at a sensitivity threshold of 10–5 (Online Supplementary Table S1). Among patients aged ≥75 years, the rates of MRD negativity were 23.5% versus 12.5% (P=0.407414), and in patients aged 65 to 74 years, the rates were 24.2% versus 8.5% (P=0.017519).
In CASTOR, among patients aged ≥75 years, higher ORR were observed with D-Vd versus Vd (95.0% versus 78.8%; P=0.1134), including higher rates of VGPR or bet- ter (70.0% versus 18.2%; P=0.0002) and CR or better (25.0% versus 3.0%; P=0.0154), respectively (Table 2). Similar findings were observed for patients aged 65 to 74 years (ORR: 82.8% versus 62.4%; P=0.0022; VGPR or bet- ter: 64.5% versus 27.1%; P<0.0001; CR or better: 33.3%
versus 10.6%; P=0.0003). The rates of MRD-negative sta- tus (10–5 sensitivity) were significantly higher with D-Vd versus Vd among patients aged 65 to 74 years (15.6% versus 2.3%; P=0.000959; Table 2). One (4.3%) patient treated with D-Vd in the subgroup of patients aged ≥75 years achieved MRD-negative status (10–5 sensitivity) compared with no patients in the Vd treatment group. Rates of MRD negativity at sensitivity thresholds of 10–4 and 10–6 are presented for both POLLUX and CASTOR in the Online Supplementary Table S2.
In patients who received one prior line of therapy, a higher proportion of patients who received D-Vd achieved MRD negativity at a sensitivity threshold of 10–5 (Online Supplementary Table S1). Among patients aged ≥75 years, the rates of MRD negativity were 12.5% versus 0% (P=0.123775), and in patients aged 65 to 74, the rates were 19.1% versus 2.6% (P=0.011285).
In POLLUX and CASTOR, all patients aged ≥75 years reported at least 1 treatment-emergent adverse event (TEAE; Table 3). In POLLUX, among patients aged ≥75 years, grade 3/4 TEAE occurred in 25 (86.2%) and 27 (77.1%) patients in the D-Rd and Rd treatment groups, respectively (Table 3). Neutropenia was the most common grade 3/4 TEAE among patients aged ≥75 years (D-Rd: 44.8%; Rd: 31.4%) and among patients aged 65 to 74 years (D-Rd: 55.3%; Rd: 39.8%). Higher rates of pneumo- nia were observed with daratumumab in both age groups. In CASTOR, among patients aged ≥75 years, grade 3/4
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haematologica | 2020; 105(2)