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M.-V. Mateos et al.
are aged >75 years, but conversely this age group is under- represented in clinical studies.22 To determine if treatment strategies are safe and effective for elderly patients with MM, subgroup analyses of clinical trial data are needed. In the current sub-analysis of POLLUX and CASTOR, the efficacy and safety of daratumumab in combination with standard-of-care regimens were evaluated in patients aged ≥75 years and 65 to 74 years.
Efficacy results were consistent with those observed in the overall study populations, showing significantly pro- longed PFS for patients aged ≥75 years and 65 to 74 years. In both studies, ORR were significantly higher with dara- tumumab versus standard-of-care treatment in patients aged 65 to 74 years and numerically higher in patients aged ≥75 years, with significantly higher rates of CR or better and VGPR or better in both age categories. While responses were considerably deeper among patients treat- ed with daratumumab, the lack of statistical significance
observed with ORR between groups may be due in part to the small number of patients aged ≥75 years in POLLUX (D-Rd, n=29; Rd, n=35) and CASTOR (D-Vd, n=23; Vd, n=35). Consistent with the overall study populations, deeper responses with daratumumab translated to a high- er proportion of patients who achieved MRD-negative status. In both studies, safety analyses identified that the rates of common grade 3/4 hematologic TEAE were simi- lar to those of the overall study populations.14,15 Importantly, IRR were manageable and did not result in treatment discontinuations. While the incidence of grade 3/4 IRR was numerically higher for patients aged ≥75 years versus patients aged 65-74 years (13.8% versus 4.9%) and what was reported for the primary analysis of POL- LUX (grade 3 IRR; 5.3%),14 a larger sample size is needed to appropriately determine if this age group is more sus- ceptible to experiencing an IRR.
There are limited clinical trial data focused on elderly
Table 2. Summary of response rates and MRD (10–5 sensitivity threshold) among patients aged 65 to 74 years and ≥75 years in POLLUX and CASTOR.
Response ratea, n (%)a
ORR ≥CR
sCR
CR ≥VGPR
VGPR PR
MR SD
PD
NE
MRDb (10–5 sensitivity threshold)
Patients evaluated, n
MRD negative, n (%)
Response ratea, n (%)
ORR ≥CR
sCR
CR ≥VGPR
VGPR PR
MR SD
PD
NE
MRDb (10–5 sensitivity threshold)
Patients evaluated, n
MRD negative, n (%)
D-Rd (n=281)
261 (92.9) 144 (51.2) 73 (26.0) 71 (25.3) 221 (78.6) 77 (27.4) 40 (14.2) 5 (1.8) 13 (4.6)
ITT
Rd (n=276)
211 (76.4) 58 (21.0) 24 (8.7) 34 (12.3) 132 (47.8) 74 (26.8) 79 (28.6) 26 (9.4) 33 (12.0)
P
<0.0001 <0.0001
<0.0001
POLLUX
65-74 years D-Rd Rd
(n=122) (n=106)
113 (92.6) 85 (80.2) 61 (50.0) 24 (22.6) 31 (25.4) 10 (9.4) 30 (24.6) 14 (13.2) 93 (76.2) 52 (49.1) 32 (26.2) 28 (26.4) 20 (16.4) 33 (31.1) 1 (0.8) 9 (8.5)
P
0.0057 <0.0001
<0.0001
D-Rd (n=29)
27 (93.1) 16 (55.2) 10 (34.5) 6 (20.7) 22 (75.9) 6 (20.7) 5 (17.2) 0
≥75 years Rd (n=34)
26 (76.5) 3 (8.8) 1 (2.9) 2 (5.9) 14 (41.2) 11 (32.4) 12 (35.3) 5 (14.7) 3 (8.8)
P
0.0740 <0.0001
0.0059
0.014464
7 (5.7) 11 (10.4)
0 4(1.4) 0 1(0.9) 0 0
2 (6.9)
2(0.7) 2(0.7) 1(0.8) 0 0 0
286
75 (26.2)
D-Vd (n=240)
201 (83.8) 69 (28.8) 21 (8.8) 48 (20.0) 149 (62.1) 80 (33.3) 52 (21.7) 9 (3.8) 23 (9.6)
283
18 (6.4)
ITT
Vd (n=234)
148 (63.2) 23 (9.8) 6 (2.6) 17 (7.3) 68 (29.1) 45 (19.2) 80 (34.2) 20 (8.5) 47 (20.1)
<0.000001
P
<0.0001 <0.0001
<0.0001
124 108
29 (23.4) 9 (8.3)
CASTOR
65-74 years D-Vd Vd
(n=93) (n=85)
77 (82.8) 53 (62.4) 31 (33.3) 9 (10.6) 12 (12.9) 2 (2.4) 19 (20.4) 7 (8.2) 60 (64.5) 23 (27.1) 29 (31.2) 14 (16.5) 17 (18.3) 30 (35.3) 2 (2.2) 4 (4.7) 13 (14.0) 18 (21.2)
0.001520
P
0.0022 0.0003
<0.0001
29
8 (27.6)
D-Vd (n=20)
19 (95.0) 5 (25.0) 2 (10.0) 3 (15.0) 14 (70.0) 9 (45.0) 5 (25.0) 0
35
2 (5.7)
≥75 years
Vd P
(n=33)
26 (78.8) 1 (3.0) 0
1 (3.0) 6 (18.2) 5 (15.2) 20 (60.6) 4 (12.1) 3 (9.1)
5(2.1) 16(6.8) 0
2(0.8) 3(1.3) 1(1.1) 0 0 0
251 247 96 87 23 35
29 (11.6) 6 (2.4) 0.000034 15 (15.6) 2 (2.3) 0.000959 1 (4.3) 0
1 (5.0)
10(11.8) 0 0
0.1134 0.0154
0.0002
0.170712
MRD: minimal residual disease; ITT: intent-to-treat; D-Rd: daratumumab/lenalidomide/dexamethasone; Rd: lenalidomide/dexamethasone; ORR: overall response rate; CR: com- plete response; sCR: stringent complete response;VGPR: very good partial response; PR: partial response; MR: minimal response; SD: stable disease; PD: progressive disease; NE: not evaluated; ; D-Vd: daratumumab/bortezomib/dexamethasone;Vd: bortezomib/dexamethasone. aResponse-evaluable population. bBased on the ITT analysis set.
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