Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Multiple myeloma gammopathies

Phase 1 study of the anti-BCMA antibody-drug conjugate AMG 224 in patients with relapsed/refractory multiple myeloma

Leukemia volume 35, pages 255–258 (2021)Cite this article

Subjects

Outcomes are poor for patients with relapsed or refractory (R/R) multiple myeloma (MM), with median overall survival of 13 months for patients refractory to proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) and 8.6 months for those refractory to anti-CD38 monoclonal antibodies (ranging from 5.6–11.2 months, depending on whether refractory to PIs and IMiDs as well) [1, 2]. Thus, novel therapies for R/R MM are needed.

The selective and high expression of B-cell maturation antigen (BCMA) by malignant plasma cells and low expression in nonplasma cells makes it an attractive therapeutic target in MM [3,4,5]. AMG 224 is an antibody-drug conjugate (ADC) consisting of an antihuman BCMA IgG1 antibody conjugated with mertansine (DM1), an antitubulin maytansinoid, through a noncleavable linker. Based on the therapeutic potential of targeting BCMA in MM, a multicenter, phase 1, open-label, first-in-human study was conducted investigating the safety and tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and efficacy of AMG 224 in patients with R/R MM with ≥3 lines of prior therapy including an IMiD and PI (NCT02561962).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Mean (±SD) pharmacokinetic profile of AMG 224 following intravenous administration every 3 weeks in the dose escalation and dose expansion in cycle 1.
Fig. 2: Summary of efficacy.

References

  1. Kumar SK, Dimopoulos MA, Kastritis E, Terpos E, Nahi H, Goldschmidt H, et al. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia. 2017;31:2443–8.

    Article  CAS  Google Scholar 

  2. Gandhi UH, Cornell RF, Lakshman A, Gahvari ZJ, McGehee E, Jagosky MH, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia. 2019;33:2266–75.

    Article  CAS  Google Scholar 

  3. Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19:2048–60.

    Article  CAS  Google Scholar 

  4. Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, et al. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood. 2004;103:689–94.

    Article  CAS  Google Scholar 

  5. Darce JR, Arendt BK, Wu X, Jelinek DF. Regulated expression of BAFF-binding receptors during human B cell differentiation. J Immunol. 2007;179:7276–86.

    Article  CAS  Google Scholar 

  6. Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117:4691–5.

    Article  CAS  Google Scholar 

  7. Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, et al. Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study. Blood Cancer J. 2019;9:37.

    Article  Google Scholar 

  8. Masters JC, Nickens DJ, Xuan D, Shazer RL, Amantea M. Clinical toxicity of antibody drug conjugates: a meta-analysis of payloads. Investig New Drugs. 2018;36:121–35.

    Article  CAS  Google Scholar 

  9. Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, et al. Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018;19:1641–53.

    Article  CAS  Google Scholar 

  10. Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020;21:207–21.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Amgen funded the study and analyses. Ben Scott, PhD (Scott Medical Communications, LLC), provided medical writing assistance funded by Amgen Inc., as did Susanna Mac, MD, PhD, of Amgen Inc.

Author information

Authors and Affiliations

  1. Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Hans C. Lee

  2. Center for Multiple Myeloma, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Noopur S. Raje

  3. Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA

    Ola Landgren

  4. Clinical Pharmacology Modeling & Simulation, Amgen Inc., South San Francisco, CA, USA

    Vijay V. Upreti

  5. Bioanalytical Sciences, Amgen Inc., Thousand Oaks, CA, USA

    Jin Wang

  6. Clinical Biomarkers & Diagnostics, Amgen Inc., South San Francisco, CA, USA

    Ariel A. Avilion & Xuguang Hu

  7. Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA, USA

    Erik Rasmussen

  8. Clinical Development, Amgen Inc., Thousand Oaks, CA, USA

    Gataree Ngarmchamnanrith

  9. Translational Medicine, Amgen Inc., South San Francisco, CA, USA

    Hisaki Fujii

  10. Malignant Haematology & Stem Cell Transplantation Service, The Alfred Hospital, Monash University, Melbourne, VIC, Australia

    Andrew Spencer

Authors
  1. Hans C. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Noopur S. Raje
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ola Landgren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vijay V. Upreti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ariel A. Avilion
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xuguang Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Erik Rasmussen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gataree Ngarmchamnanrith
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hisaki Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Andrew Spencer
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The corresponding author confirms that he has had full access to the data in the study and final responsibility for the decision to submit for publication. HCL: data collection and interpretation. NSR: data collection, data interpretation. OL: data analysis and interpretation. VVU: study design, data collection, data analysis, data interpretation. JW: data collection, data analysis. AAA: data analysis and interpretation. XH: data analysis and interpretation. ER: data analysis and interpretation. GN: study design, data interpretation. HF: study design, data interpretation. AS: data collection, data interpretation. All authors reviewed or revised the paper.

Corresponding author

Correspondence to Hans C. Lee.

Ethics declarations

Conflict of interest

HCL: research support and consultant/advisor (Amgen, Celgene, Janssen, and Takeda), consultant/advisor (GlaxoSmithKline and Sanofi), and research support (Daiichi Sankyo). NSR: consultant (Amgen Inc., Takeda, Celgene, Bristol-Myers Squibb, Janssen, Bluebird, and Karyopharm). OL: research funding (National Institutes of Health, U.S. Food and Drug Administration, Multiple Myeloma Research Foundation, International Myeloma Foundation, Leukemia and Lymphoma Society, Perelman Family Foundation, Rising Tide Foundation, Amgen Inc., Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, and Karyopharm); honoraria and advisory boards (Adaptive, Amgen Inc., Binding Site, Bristol-Myers Squibb, Celgene, Cellectis, Glenmark, Janssen, Juno, Pfizer); and Independent Data Monitoring Committees (Takeda, Merck, and Janssen). VVU, JW, AAA, XH, ER, GN, and HF: employment by and stock ownership in Amgen Inc. AS: consultant (Celgene, Janssen, Secura Bio, Specialised Therapeutics Australia, AbbVie, Servier, HaemaLogiX, and Sanofi); speaker’s bureau (Celgene, Janssen, and Takeda); grant/Research Support (Celgene, Janssen, Amgen Inc., Takeda, Servier, HaemaLogiX); honoraria (Celgene, Janssen, Amgen Inc., Takeda, Secura Bio, Specialised Therapeutics Australia, AbbVie, Servier, HaemaLogiX, and Sanofi).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, H.C., Raje, N.S., Landgren, O. et al. Phase 1 study of the anti-BCMA antibody-drug conjugate AMG 224 in patients with relapsed/refractory multiple myeloma. Leukemia 35, 255–258 (2021). https://doi.org/10.1038/s41375-020-0834-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-020-0834-9

This article is cited by

Search

Advanced search

Quick links