Allocation and validation of the second revision of the International Staging System in the ICARIA-MM and IKEMA studies
The International Staging System for multiple myeloma recently underwent a second revision (R2-ISS) to include gain/amplification of 1q21 and account for the additive prognostic significance of multiple high-risk features. The phase 3 ICARIA-MM (isatuximab-pomalidomide-dexamethasone vs. pomalidomide-dexamethasone) and IKEMA (isatuximab-carfilzomib-dexamethasone vs. carfilzomib-dexamethasone) studies provide large datasets for retrospectively validating the prognostic value of the R2-ISS in relapsed/refractory multiple myeloma. Of 609 pooled patients, 68 (11.2%) were reclassified as R2-ISS stage I, 136 (22.3%) as R2-ISS stage II, 204 (33.5%) as R2-ISS stage III, 55 (9.0%) as stage IV, and 146 (24.0%) "Not classified". Median progression-free survival was shorter among those reclassified as R2-ISS stage II (HR 1.52, 95% CI 0.979-2.358), stage III (HR 2.59, 95% CI 1.709-3.923), and stage IV (HR 3.51, 95% CI 2.124-5.784) versus stage I. Adding isatuximab led to longer progression-free survival versus doublet therapy (adjusted HR 0.544 [95% CI 0.436-0.680]), with a consistent treatment effect observed across all R2-ISS stages. This is the first study to validate the R2-ISS with novel agents, including anti-CD38 monoclonal antibodies, and to show that R2-ISS, as a prognostic scoring system, can be applied to patients with relapsed/refractory multiple myeloma.
Authors
- Pieter Sonneveld (ORCID: https://orcid.org/0000-0002-0808-2237)
- Mattia D’Agostino (ORCID: https://orcid.org/0000-0002-1711-6996)
- Zandra Klippel
- Keisuke Tada (ORCID: https://orcid.org/0000-0003-3051-5841)
- Ivan Špıčka (ORCID: https://orcid.org/0000-0002-5451-5283)
- Paul Gerard Guy Richardson (ORCID: https://orcid.org/0000-0002-7426-8865)
- Helgi van de Velde (ORCID: https://orcid.org/0009-0004-4126-8289)
- Rick Zhang
- Marcelo Capra (ORCID: https://orcid.org/0000-0002-5224-1979)
- Joseph Mıkhael (ORCID: https://orcid.org/0000-0001-9670-2864)
- Thomas G. Martin (ORCID: https://orcid.org/0000-0002-9133-9813)
- Christina Tekle
- Sandrine Macé (ORCID: https://orcid.org/0000-0001-9263-6994)
- Meral Beksaç (ORCID: https://orcid.org/0000-0003-1797-8657)
- Kamlesh Bisht (ORCID: https://orcid.org/0009-0003-3808-924X)
- Aurore Perrot (ORCID: https://orcid.org/0000-0003-0131-8689)
- Philippe Moreau (ORCID: https://orcid.org/0000-0003-1780-8746)
- Taro Fukao
Institutions
- Translational Genomics Research Institute (US)
- City Of Hope National Medical Center (US)
- Université Toulouse III - Paul Sabatier (FR)
- Harvard University (US)
- Ankara University (TR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- University of California, San Francisco (US)
- Charles University (CZ)
- Erasmus MC (NL)
- Sanofi (France) (FR)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- City of Hope (US)
- Sanofi (United States) (US)
- Dana-Farber Cancer Institute (US)
- Sanofi (Japan) (JP)
- Erasmus MC Cancer Institute (NL)
- Hospital Mãe de Deus (BR)
Publication Details
- Journal
- Blood Cancer Journal
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1038/s41408-024-01149-w
- Citations
- 5
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 2.27
Funders
- Sanofi