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Background <p>Elranatamab is a BCMA-CD3 bispecific antibody approved for the treatment of relapsed or refractory multiple myeloma. Cytokine release syndrome is one of the most common adverse events associated with bispecific antibodies.</p> Objective <p>We aimed to determine the optimal elranatamab dosing regimen for mitigating cytokine release syndrome.</p> Patients and Methods <p>Safety, pharmacokinetics, and exposure–response were analyzed across four clinical studies (MagnetisMM-1, MagnetisMM-2, MagnetisMM-3, and MagnetisMM-9). Different priming regimens evaluated across these studies included a one-step-up dose priming regimen of 44 mg with or without premedication, a two-step-up dose priming regimen of 12 mg on day 1 and 32 mg on day 4 with premedication, and a two-step-up dose priming regimen of 4 mg on day 1 and 20 mg on day 4 with premedication.</p> Results <p>The maximum elranatamab serum concentration on day 1 was positively associated with any-grade and grade ≥&#xa0;2 cytokine release syndrome. A slower time to maximum serum concentration and a lower dose-normalized maximum serum concentration were observed with subcutaneous versus intravenous administration, supporting subcutaneous dosing to help mitigate cytokine release syndrome.</p> Conclusions <p>Based on the incidence, severity, and predictable profile of cytokine release syndrome, the 12/32-mg priming-dose regimen with premedication was determined to be the optimal regimen before the first full dose of 76&#xa0;mg on day 8.</p> Clinical Trial Registration <p>ClinicalTrials.gov identifiers: NCT03269136, NCT04798586, NCT04649359, and NCT05014412.</p>

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Dose Optimization of Elranatamab to Mitigate the Risk of Cytokine Release Syndrome in Patients with Multiple Myeloma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月25日

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  • Mohamed Elmeliegy,
  • Andrea Viqueira,
  • Erik Vandendries,
  • Anne Hickman,
  • Umberto Conte,
  • Donald Irby,
  • Jennifer Hibma,
  • Hoi-Kei Lon,
  • Joseph Piscitelli,
  • Pooneh Soltantabar,
  • Athanasia Skoura,
  • Sibo Jiang,
  • Diane Wang

摘要

Background

Elranatamab is a BCMA-CD3 bispecific antibody approved for the treatment of relapsed or refractory multiple myeloma. Cytokine release syndrome is one of the most common adverse events associated with bispecific antibodies.

Objective

We aimed to determine the optimal elranatamab dosing regimen for mitigating cytokine release syndrome.

Patients and Methods

Safety, pharmacokinetics, and exposure–response were analyzed across four clinical studies (MagnetisMM-1, MagnetisMM-2, MagnetisMM-3, and MagnetisMM-9). Different priming regimens evaluated across these studies included a one-step-up dose priming regimen of 44 mg with or without premedication, a two-step-up dose priming regimen of 12 mg on day 1 and 32 mg on day 4 with premedication, and a two-step-up dose priming regimen of 4 mg on day 1 and 20 mg on day 4 with premedication.

Results

The maximum elranatamab serum concentration on day 1 was positively associated with any-grade and grade ≥ 2 cytokine release syndrome. A slower time to maximum serum concentration and a lower dose-normalized maximum serum concentration were observed with subcutaneous versus intravenous administration, supporting subcutaneous dosing to help mitigate cytokine release syndrome.

Conclusions

Based on the incidence, severity, and predictable profile of cytokine release syndrome, the 12/32-mg priming-dose regimen with premedication was determined to be the optimal regimen before the first full dose of 76 mg on day 8.

Clinical Trial Registration

ClinicalTrials.gov identifiers: NCT03269136, NCT04798586, NCT04649359, and NCT05014412.