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KCyd in high-risk NDMM
Table 1. Patients’ characteristics at baseline.
All patients
Standard-risk patients n=57
72 (68-75) 16 (28%)
24 (42%)
33 (58%)
19 (33%) 17 (30%) 21 (37%)
- - -
34 (60%) 18 (32%) 5 (9%)
288 (198-359)
13 (23%)
High-risk patients n=37
72 (68-74) 8 (22%)
16 (43%)
21 (57%)
9 (24%) 15 (41%) 13 (35%)
Age
Median (range) ≥75 years, n (%)
Sex, n (%)
Male
Female ISS, n (%)
I II III
FISH, n (%)
n=94
72 (68-75) 24 (26%)
40 (43%)
54 (57%)
28 (30%) 32 (34%) 34 (36%)
t(4;14)
t(14;16)
del17p
≥2CA* 1(1%) - 1(3%)
Frailty Score, n (%) Fit
Intermediate
Frail
LDH [UI/mmol]
Median (range)
Missing
53 (56%) 29 (31%) 12 (13%)
282.5 (168-361)
18 (19%)
19 (51%) 11 (30%) 7 (19%)
274 (154-386)
5 (14%)
12 (13%) 4 (4%) 22 (23%)
12 (32%) 4 (11%) 22 (59%)
ISS: International Staging System; FISH: fluorescence in situ hybridization; LDH: lactate dehydrogenase; n: number; CA: cytogenetic abnormalities. *At least two cytogenetic abnormalities among t(4;14), t(14;16) and del17p.
Results
Among the 121 patients enrolled in the two trials (63 patients from IST-CAR-561 and 58 patients from IST- CAR-506), complete cytogenetic data were available for 94 patients: 57 patients (61%) in the SR and 37 (39%) in the HiR group according to FISH analysis. Among patients in the HiR group, t(4;14) was present in 12 patients (13%), t(14;16) in four patients (4%), and del17p in 22 (23%) patients. The median percentage of plasma cells with t(4;14) was 80% (range: 15-99), with t(14;16) was 85%, and with del17p was 34% (range: 10-95).
Baseline characteristics were well balanced between SR and HiR patients and are summarized in Table 1. Median age at enrollment was 72 years (range: 60-86) for the entire population; no significant differences in terms of age, sex, ISS stage or frailty status were observed between the two groups.
Median follow-up was 38 months for the entire cohort. Ninety-two of 94 patients started the induction phase (1 withdrew consent and 1 was lost to follow-up before commencing therapy): 56 of 57 in the SR and 36 of 37 in the HiR group. Seventy patients (74%) started the mainte- nance phase: 42 (74%) in the SR and 28 (76%) in the HR group (P=1.00). The median duration of treatment was 16.9 months in SR patients and 14.6 months in HiR patients.
Responses to therapy are shown in Table 2. No signifi- cant differences in terms of overall response rate (ORR) were observed between SR and HiR patients both after the induction phase (86% and 92%, respectively; P=0.52)
and overall (induction and maintenance phases; 88% and 95%, respectively; P=0.47). In addition, the rate of com- plete response (CR) after the induction phase (19% vs. 22%; P=0.80) and the maintenance phase (23% vs. 24%; P=1) was similar in SR and in HiR patients.
Median PFS was similar between SR (not reached [NR]) and HiR (27.8 months) patients (HR 0.81, 95%CI: 0.44- 1.48; P=0.50); at 3 years, 52% and 43% of patients were alive and free from progression in the two groups, respec- tively. Median PFS-2 was NR and 44.1 months, respective- ly (HR 0.67, 95%CI: 0.32-1.39; P=0.28). No significant dif- ferences were observed in median OS in SR and HiR patients, respectively (median OS: NR vs. NR, HR 0.72, 95%CI: 0.34-1.52; P=0.38), with 78% of patients in the SR and 73% in the HiR group alive at 3 years from diagnosis (Figure 1A-C).
No significant differences in terms of median PFS, PFS-2 and OS were observed among patients with or without del17p (PFS: 35 vs. 35.7 months, HR 0.92, 95%CI: 0.47- 1.82, P=0.82; PFS-2: 44.1 months vs. NR, HR 1.20, 95%CI: 0.55-2.64, P=0.65; OS: 47.5 months vs. NR, HR 1.17, 95% CI: 0.52-2.62, P=0.70) (Figure 2). When adopting a higher cut-off for del17p positivity (>20%), no significant differ- ence in PFS was reported between del17p-negative and del17p-positive patients (median: 35.7 vs. 35 months).
Discussion
The aim of our analysis was to evaluate whether a carfilzomib-based upfront treatment could abrogate the
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