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Age-based subgroup analysis of CASTOR and POLLUX
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ISS staging, n (%)b I
II
III
Time from diagnosis, years
Median (range)
Prior lines of therapy, n (%)
1 2 3 >3
Cytogenetic profilec, n (%)
N
Standard
High
34 (35.4) 37 (38.5) 25 (26.0)
4.0 (0.7-20.7)
47 (49.0) 29 (30.2) 15 (15.6) 5 (5.2)
33 (37.9) 32 (36.8) 22 (25.3)
3.9 (0.9-17.2)
38 (43.7) 23 (26.4) 15 (17.2) 11 (12.6)
6 (26.1) 7 (30.4) 10 (43.5)
4.6 (1.0-14.7)
8 (34.8) 8 (34.8) 3 (13.0) 4 (17.4)
13 (37.1) 13 (37.1) 9 (25.7)
3.6 (1.2-18.6)
17 (48.6) 13 (37.1) 2 (5.7) 3 (8.6)
72 71 11 28
60 (83.3) 53 (74.6) 9 (81.8) 22 (78.6)
12 (16.7) 18 (25.4) 2 (18.2) 6 (21.4)
D-Rd: daratumumab/lenalidomide/dexamethasone; Rd: lenalidomide/dexamethasone; ECOG: Eastern Cooperative Oncology Group; daratumumab/bortezomib/dexametha- sone;Vd:bortezomib/dexamethasone.aPercentages may not add up to 100% due to rounding.bISS staging is derived based on the combination of serum β2-microglobulin and albumin. cCytogenetic risk determined by next-generation sequencing.
median (range) duration of follow-up of 19.4 (0-27.7) months. Of the 498 patients enrolled in CASTOR, 23/251 (D-Vd) and 35/247 (Vd) were aged ≥75 years, and 96/251 (D-Vd) and 87/247 (Vd) were aged 65 to 74 years. In both studies, demographic and baseline clinical characteristics were well balanced between treatment groups (Table 1). In POLLUX, among patients aged ≥75 years, 3/13 (23.1%) patients in the D-Rd group and 4/16 (25.0%) patients in the Rd group had high-risk cytogenetic abnormalities. Similarly, among patients aged ≥75 years in CASTOR, 2/11 (18.2%) patients in the D-Vd group and 6/28 (21.4%) patients in the Vd group had high cytogenetic risk. Among patients aged 65 to 74 years in POLLUX, 11 (16.4%) patients in the D-Rd group and 13 (22.8%) of patients in the Rd group had high cytogenetic risk abnormalities. Similarly, among patients aged 65 to 74 years in CASTOR, 12 (16.7%) patients in the D-Vd group and 18 (25.4%) patients in the Vd group had high cytogenetic risk.
The dispositions of patients according to age from POLLUX and CASTOR are summarized in Figure 1. In POLLUX, nine (31.0%) patients aged ≥75 years who were treated with D-Rd and 24 (68.6%) patients who were treated with Rd discontinued treatment. In CASTOR, 11 (55.0%) patients aged ≥75 years who received D-Vd and 15 (42.9%) patients who were treated with Vd discontin- ued treatment. Among patients aged ≥75 years who were randomized to D-Vd, 3 (13.0%) did not receive treatment. Similar findings were observed in the patients aged 65 to 74 years: in POLLUX, 51 (41.5%) patients who were treat- ed with D-Rd and 76 (70.4%) patients who received Rd discontinued treatment, and in CASTOR, 56 (59.6%) patients who were treated with D-Vd and 44 (51.2%) patients who received Vd discontinued treatment.
In POLLUX, the median dose intensity of lenalidomide was generally lower in both treatment arms for patients aged ≥75 years (D-Rd, 210.00 mg/cycle; Rd, 305.00 mg/cycle) compared with patients aged 65 to 74 years (D-Rd, 333.93 mg/cycle; Rd, 420.00 mg/cycle). In CAS- TOR, the median dose intensity of bortezomib was simi- lar among patients aged ≥75 years (D-Vd, 4.06
mg/m2/cycle; Vd, 4.37 mg/m2/cycle) and 65 to 74 years (D- Vd, 4.56 mg/m2/cycle; Vd, 4.70 mg/m2/cycle).
In POLLUX, in the ITT population, the clinical benefit of D-Rd over Rd was maintained after a median follow-up of 25.4 months (Figure 2). PFS was significantly prolonged with D-Rd versus Rd in the ITT population (median: not reached versus 17.5 months; HR, 0.41; 95% CI, 0.31-0.53; P<0.0001; Figure 2A),20 with 18-month PFS rates of 75.3% and 48.5%, respectively. Similarly, PFS was significantly prolonged with D-Rd compared with Rd in patients aged ≥75 years (median: 28.9 versus 11.4 months; HR, 0.27; 95% CI, 0.10-0.69; P=0.0042; Figure 2A), with 18-month PFS rates of 86.2% versus 36.9%, respectively. PFS was also significantly prolonged with D-Rd versus Rd in patients aged 65 to 74 years (median: not reached versus 17.1 months; HR, 0.40; 95% CI, 0.27-0.60; P<0.0001; Figure 2B), with 18-month PFS rates of 72.0% and 48.7%, respectively. At the time of the clinical cut-off, overall sur- vival (OS) data were immature. Survival follow-up for POLLUX will continue until 330 deaths are observed in the ITT population.
In CASTOR, in the ITT population, the clinical benefit of D-Vd over Vd was maintained after a median follow-up of 19.4 months (Figure 2). PFS was significantly prolonged with D-Vd versus Vd in the ITT population (median: 16.7 versus 7.1 months; HR, 0.31; 95% CI, 0.24-0.39; P<0.0001; Figure 2C), with 18-month PFS rates of 48.0% versus 7.9%, respectively.21 Similarly, PFS was significantly prolonged with D-Vd compared with Vd in patients aged ≥75 years (median: 17.9 versus 8.1 months; HR, 0.26; 95% CI, 0.10- 0.65; P=0.0022; Figure 2C), with 18-month PFS rates of 45.8% versus 0%, respectively. PFS was also significantly prolonged for D-Vd versus Vd in patients aged 65 to 74 years (median: 18.9 versus 6.1 months; HR, 0.25; 95% CI, 0.16-0.40; P<0.0001; Figure 2D). Follow-up for OS in CASTOR will continue until 320 deaths are reported in the ITT population, per protocol.
In POLLUX, among patients aged ≥75 years, higher ORR were observed with D-Rd versus Rd (93.1% versus 76.5%; P=0.0740), with significantly higher rates of VGPR
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