TY - JOUR
T1 - Allocation and validation of the second revision of the International Staging System in the ICARIA-MM and IKEMA studies
AU - Richardson, Paul G.
AU - Perrot, Aurore
AU - Mikhael, Joseph
AU - Martin, Thomas
AU - Beksac, Meral
AU - Spicka, Ivan
AU - Capra, Marcelo
AU - D’Agostino, Mattia
AU - Sonneveld, Pieter
AU - Bisht, Kamlesh
AU - Fukao, Taro
AU - Zhang, Rick
AU - Tada, Keisuke
AU - Tekle, Christina
AU - Macé, Sandrine
AU - Klippel, Zandra
AU - van de Velde, Helgi
AU - Moreau, Philippe
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/11/28
Y1 - 2024/11/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85210476849&partnerID=8YFLogxK
U2 - 10.1038/s41408-024-01149-w
DO - 10.1038/s41408-024-01149-w
M3 - Article
C2 - 39609425
AN - SCOPUS:85210476849
SN - 2044-5385
VL - 14
JO - Blood Cancer Journal
JF - Blood Cancer Journal
IS - 1
M1 - 209
ER -