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How to sequence BCMA-directed therapies in early relapsed/ refractory multiple myeloma
At the ESH 7th Translational Research Conference:
Multiple Myeloma
with Martin Kaiser, Mohamad Mohty, and Rakesh Popat
Saturday, October 5, 2024 | 09:10-10:10 CEST
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Isatuximab is an IgG1 monoclonal antibody which targets CD38 on myeloma cells. Therapeutic effects include induced apoptosis, immunomodulation, and ectoenzyme inhibition.1 The combination of isatuximab, carfilzomib, and dexamethasone (isa-Kd) was approved by both the U.S. Food and Drug Administration and the European Commission in 2021 for the treatment of patients diagnosed with relapsed/refractory multiple myeloma who have received 1–3 lines of prior therapy.
Approval was based on results obtained from the phase III IKEMA trial (NCT03275285) investigating isa-Kd versus carfilzomib and dexamethasone (Kd).
During the 20th International Myeloma Society Annual Congress, Moreau presented the final overall survival (OS) analysis from the IKEMA trial. Here, we summarize the key points from the presentation. For more information on the IKEMA trial, see the dedicated page on the Multiple Myeloma Hub.
Table 1. Baseline patient characteristics*
Characteristic, % (unless otherwise stated) |
Isa-Kd (n = 179) |
Kd (n = 123) |
---|---|---|
Median age, years |
65.0 |
63.0 |
ISS stage |
||
I |
49.7 |
57.7 |
II |
35.2 |
25.2 |
III |
14.5 |
16.3 |
Cytogenetic risk |
||
High |
23.5 |
25.2 |
Standard |
63.7 |
63.4 |
Missing |
12.8 |
11.4 |
Number of prior lines of therapy |
||
1 |
44.1 |
44.7 |
2 |
35.8 |
29.3 |
3 |
18.4 |
24.4 |
Prior PI |
92.7 |
85.4 |
Prior IMiD |
76.0 |
81.3 |
Patients refractory to |
||
IMiD |
43.6 |
47.2 |
Lenalidomide |
31.8 |
34.1 |
PI |
31.3 |
35.8 |
Last regimen |
49.7 |
59.3 |
IMiD, immunomodulatory agent; ISS, International Staging System; isa-Kd, isatuximab, carfilzomib, and dexamethasone; Kd, |
Figure 1. Final PFS and PFS2 analysis for patients treated with isa-Kd and Kd*
Isa-Kd, isatuximab, carfilzomib, and dexamethasone; Kd, carfilzomib and dexamethasone; PFS, progression-free survival; PFS2, second progression-free survival.
†Progression-free survival is defined as the time from randomization to disease progression or subsequent therapy/death.
*Adapted from Moreau.1
Patients treated with isa-Kd benefited from a more favorable OS compared with Kd treatment. This represents the longest OS achieved in a phase III lenalidomide-free trial in the relapsed setting. The isa-Kd treatment arm also experienced a more favorable time to next treatment and second progression-free survival compared with the Kd arm. Moreover, the benefit of isatuximab was sustained through subsequent lines of therapy. Overall, the final analysis of the trial supports the use of isa-Kd as the standard of care option for patients diagnosed with relapsed/refractory multiple myeloma.
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