Elotuzumab in combination with pomadomide and dexamethasone for relapsed/refractory multiple myeloma: results from the final total survival analysis of the ELOQUENT-3 Phase II trial

Significant progress has been made in the treatment of multiple myeloma (MM) over the past 10-15 years, but the 5-year relative survival rate is only 55.

Elotuzumab is a fully humanized monoclonal antibody that targets SLAMF7 with a combination therapy regimen that improves the prognosis

Preclinical studies in mice have shown that elotuzumab in combination with pomadomide and dexamethasone (EPd) has a synergistic anti-tumor effect, and it is assumed that similar effects

The primary endpoints of the study were investigator-assessed PFS, and the secondary endpoints were objective response rate (ORR) and OS

A total of 117 patients with RRMM were included in this study, 60 in the EPd group and 57 in

Figure 1

Table 1

Treatment

• Survival analysis

As of data deadline (11 January 2021), 78 patients had died (37 in the EPd group and 41 in the Pd group)
after at least 45 months of follow-up.

The most common cause of death in both groups was disease progression (41.
7% in the EPd group and 49.
1%
in the Pd group).

The median OS was 17.
4 months (95% CI, 13.
8-27.
7) in the Pd group and 29.
8 months (95% CI, 22.
9-45.
7; HR=0.
59 [95% CI, 0.
37-0.
93], P=0.
0217; Figure 2).


Patients in the EPd group had a 41%
lower risk of death compared to the Pd group.

The 1-, 2-, and 3-year OS rates were higher in the EPd group than in the Pd group (79% vs 68%, 63% vs 44%, 39% vs 29%)
.

Figure 2

In most subgroups, the OS benefit observed in the EPd group was consistent (Figure 3
).

In patients aged ≥75 years (median OS: 34.
4 months vs 14.
7 months; HR =0.
36 [95% CI, 0.
13 to 1.
01]), lenalidomide, and one PI are refractory (median OS: 28.
3 months vs 17.
4 months; HR =0.
74 [95% CI, 0.
44 to 1.
25]), patients who had previously received ≥ 4-line therapy (median OS: 29.
8 months vs 16.
0 months; HR =0.
42 [95% CI, 0.
20 to 0.
89]) and patients with lenalidomide as the most recent first-line treatment (median OS: 32.
0 months vs 20.
8 months; In HR=0.
55 [95% CI, 0.
29-1.
04]), an improvement trend
in os-assay in the EPd group was observed compared with the Pd group.

Figure 3

• security

The most common levels of AE are anemia (EPd, 28.
3%; Pd, 38.
2%) and neutropenia (EPd, 26.
7%; Pd, 30.
9 per cent (table 2
).

The most common grade 3/4 AE is neutropenia (EPd, 15.
0%; Pd, 27.
3%) and anemia (EPd, 11.
7%; Pd，21.
8%）
。
Severe AE (SAE)
of all levels occurred in 70.
0% of patients in the EPd group and 60.
0% of patients in the Pd group.

The most common SAE was respiratory infections (EPd, 8.
3%; Pd, 5.
5%) and pneumonia (EPd, 6.
7%; Pd，9.
1%）
。

Table 2

Compared with the Pd regimen, the EPd regimen significantly reduced the risk of death in patients previously treated with lenalidomide and a PI treatment of RRMM, with a median OS increase of 1 year
.

The ELOQUENT-3 trial is the first randomized study of a triple regimen containing monoclonal antibodies and Pd, which has shown significant improvements in PFS and OS
in patients with RRMM.

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