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Positive EMA’s CHMP opinion announced for isatuximab with carfilzomib and dexamethasone in relapsed MM

Mar 3, 2021
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The Committee for Medicinal Products for Human Use (CHMP) from the European Medicines Agency (EMA) has issued on Feb 25, 2021 a positive opinion for isatuximab (isa) in combination with carfilzomib and dexamethasone (Kd), for adult patients with multiple myeloma (MM) who had been previously treated with at least one line of therapy.1

The opinion was based on the results of the phase III IKEMA study (NCT03275285) in patients with MM who had received 1−3 lines of treatment. In this study, isatuximab combined with Kd was tested against Kd only. During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the interim trial analysis was presented.2 The primary endpoint of this study was progression-free survival (PFS), while overall response rate, very good partial response, and complete response were the secondary endpoints.

After a median follow-up of 20.7 months, patients in the isa-Kd group showed improved responses compared with the Kd group in all categories (Table 1).

Table 1. Outcomes in the IKEMA trial2

Outcome

Isa-Kd (n = 179)

Kd (n = 123)

p value

≥ VGPR, %

72.6

56.1

0.0011

≥ CR, %

39.7

27.6

 

MRD-negative*, %

29.6

13

0.0004

MRD-negative + CR, %

20.1

10.6

 

CR, complete response; d, dexamethasone; Isa, isatuximab; K, carfilzomib; MRD, measurable residual disease; VGPR, very good partial response.

*MRD assessed by next-generation sequencing (NGS) at 10−5 sensitivity level.

Overall, the median PFS with isa-Kd has not been reached, but was longer than with Kd, with a hazard ratio (HR) of 0.531 (99% CI, 0.318–0.889) favoring the triplet arm. More prolonged PFS survival was associated with achieving measurable residual disease (MRD) negativity in both treatment arms (Table 2), but still, isa-Kd achieved a greater PFS benefit for both MRD-negative and MRD-positive patients.

Table 2. PFS according to treatment groups and measurable residual disease status2

PFS

HR

95% CI

Isa-Kd MRD-negative

0.578

0.052–6.405

Kd MRD-negative

Isa-Kd MRD-positive

0.670

0.452–0.993

Kd MRD-positive

d, dexamethasone; Isa, isatuximab; K, carfilzomib; MRD, measurable residual disease.

The combination of isa-Kd is not yet approved for usage in the EU; however, the final decision is expected in the coming months from the European Commission.

Isatuximab is an anti-CD38 monoclonal antibody that triggers apoptosis in MM cells and has immunomodulatory effects. It has so far been approved by the U.S. Food and Drug Administration (FDA) and the EMA in patients with relapsed/refractory MM who have been previously treated with at least two lines of therapy.

  1. European Medicines Agency (EMA). Sarclisa. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/sarclisa-0. Published Feb 26, 2021. Accessed Mar 2, 2021.
  2. Martin T, Mikhael J, Hajek R, et al. Depth of response and response kinetics of isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma: Ikema interim analysis. 2020;136(Supplement 1):7-8. DOI: https://doi.org/10.1182/blood-2020-137681

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