Page 228 - Haematologica Vol. 109 - July 2024

ARTICLE - ICARIA-MM final overall survival analysis P.G. Richardson et al.
Figure 1. Trial profile as of data cutoff for the final overall survival analysis. aInvestigator decision due to free light chain increase (N=3), physician’s decision (suspected progression, N=1), unconfirmed progression (N=1), poor compliance to protocol (N=1), in- vestigator decided to switch treatment to daratumumab-pomalidomide-dexamethasone (N=1), investigator kept the same isat- uximab-pomalidomide-dexamethasone (Isa-Pd) combination off protocol, as the product is available commercially (N=1). bPhy- sician decision. OS: overall survival.
The proportional hazard assumption was met (Schoenfeld residuals test) for the following Cox models: PFS by in- vestigator (P=0.89), OS (P=0.28), TTNT (P=0.44), and PFS2 (P=0.42).
The ORR was higher with Isa-Pd versus Pd, consistent with the primary analysis and second interim analysis (Online Supplementary Table S2; Online Supplementary Figure S3). Deeper responses were also observed with Isa-Pd versus Pd. Minimal residual disease negativity was observed in ten (6%) patients in the Isa-Pd group at the 10-5 sensitivity level (18 patients with data available) but in no patients in the Pd group (3 patients with data available; data not shown). More patients in the Isa-Pd group versus the Pd group re- ceived subsequent alkylating agents, PI, corticosteroids, and other treatments (i.e., investigational anti-neoplastic drugs, cisplatin, etoposide, and stem cells), whereas IMiD
agents were administered to a similar proportion of patients in both groups (Online Supplementary Table S3). Exploratory analysis of ORR, CR, VGPR, or PR on selected subsequent therapies with/without daratumumab are shown in Figure 4 and Online Supplementary Figure S4. Among non-daratumumab-based regimens, non-IMiD- based regimens versus IMiD-based regimens led to better response rates with Isa-Pd (28/71 [39%] vs. 3/27 [11%]). Per the inclusion criteria, patients previously failed treatment with lenalidomide and a PI.
ORR with subsequent daratumumab in any subsequent line was lower for patients in the Isa-Pd group (5/21 [24%]) vs. the Pd group (23/57 [40%]); however, rates of ≥VGPR were similar (3/21 [14%] vs. 10/57 [18%]). Daratumumab in com- bination led to improvements in both arms (Isa-Pd: 4/14 [29%]; Pd: 13/29 [45%]) versus daratumumab monotherapy
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