Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma : The HOVON-87/NMSG-18 trial
(2020) In Blood Advances 4(24). p.6298-6309- Abstract
The standard prognostic marker for multiple myeloma (MM) patients is the revised International Staging System (R-ISS). However, there is room for improvement in guiding treatment. This applies particularly to older patients, in whom the benefit/risk ratio is reduced because of comorbidities and subsequent side effects. We hypothesized that adding gene-expression data to R-ISS would generate a stronger marker. This was tested by combining R-ISS with the SKY92 classifier (SKY-RISS). The HOVON-87/NMSG-18 trial (EudraCT: 2007-004007-34) compared melphalan-prednisone-thalidomide followed by thalidomide maintenance (MPT-T) with melphalan-prednisone-lenalidomide followed by lenalidomide maintenance (MPR-R). From this trial, 168 patients with... (More)
The standard prognostic marker for multiple myeloma (MM) patients is the revised International Staging System (R-ISS). However, there is room for improvement in guiding treatment. This applies particularly to older patients, in whom the benefit/risk ratio is reduced because of comorbidities and subsequent side effects. We hypothesized that adding gene-expression data to R-ISS would generate a stronger marker. This was tested by combining R-ISS with the SKY92 classifier (SKY-RISS). The HOVON-87/NMSG-18 trial (EudraCT: 2007-004007-34) compared melphalan-prednisone-thalidomide followed by thalidomide maintenance (MPT-T) with melphalan-prednisone-lenalidomide followed by lenalidomide maintenance (MPR-R). From this trial, 168 patients with available R-ISS status and gene-expression profiles were analyzed. R-ISS stages I, II, and III were assigned to 8%, 75%, and 7% of patients, respectively (3-year overall survival [OS] rates: 80%, 65%, 33%, P 5 8 3 1023). Using the SKY92 classifier, 13% of patients were high risk (HR) (3-year OS rates: standard risk [SR], 70%; HR, 28%; P,.001). Combining SKY92 with R-ISS resulted in 3 risk groups: SKY-RISS I (SKY-SR 1 R-ISS-I; 15%), SKY-RISS III (SKY-HR 1 R-ISS-II/III; 11%), and SKY-RISS II (all other patients; 74%). The 3-year OS rates for SKY-RISS I, II, and III are 88%, 66%, and 26%, respectively (P 5 6 3 1027). The SKY-RISS model was validated in older patients from the CoMMpass dataset. Moreover, SKY-RISS demonstrated predictive potential: HR patients appeared to benefit from MPR-R over MPT-T (median OS, 55 and 14 months, respectively). Combined, SKY92 and R-ISS classify patients more accurately. Additionally, benefit was observed for MPR-R over MPT-T in SKY92-RISS HR patients only.
(Less)
- author
- Kuiper, Rowan
; Zweegman, Sonja
; van Duin, Mark
; van Vliet, Martin H.
; van Beers, Erik H.
; Dumee, Belinda
; Vermeulen, Michael
; Koenders, Jasper
; van der Holt, Bronno
; Visser-Wisselaar, Heleen
; Hansson, Markus
LU
; van der Velden, Annette W.G.
; Berna Beverloo, H.
; Stevens-Kroef, Marian
; Levin, Mark David
; Broijl, Annemiek
; Waage, Anders
and Sonneveld, Pieter
(Less) - publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood Advances
- volume
- 4
- issue
- 24
- pages
- 12 pages
- publisher
- American Society of Hematology
- external identifiers
-
- scopus:85098052619
- pmid:33351127
- ISSN
- 2473-9529
- DOI
- 10.1182/bloodadvances.2020002838
- language
- English
- LU publication?
- no
- id
- b0be74a8-342a-4951-b7c6-611f05fab7ce
- date added to LUP
- 2021-01-05 09:59:01
- date last changed
- 2024-07-26 08:31:51
@article{b0be74a8-342a-4951-b7c6-611f05fab7ce,
abstract = {{<p>The standard prognostic marker for multiple myeloma (MM) patients is the revised International Staging System (R-ISS). However, there is room for improvement in guiding treatment. This applies particularly to older patients, in whom the benefit/risk ratio is reduced because of comorbidities and subsequent side effects. We hypothesized that adding gene-expression data to R-ISS would generate a stronger marker. This was tested by combining R-ISS with the SKY92 classifier (SKY-RISS). The HOVON-87/NMSG-18 trial (EudraCT: 2007-004007-34) compared melphalan-prednisone-thalidomide followed by thalidomide maintenance (MPT-T) with melphalan-prednisone-lenalidomide followed by lenalidomide maintenance (MPR-R). From this trial, 168 patients with available R-ISS status and gene-expression profiles were analyzed. R-ISS stages I, II, and III were assigned to 8%, 75%, and 7% of patients, respectively (3-year overall survival [OS] rates: 80%, 65%, 33%, P 5 8 3 10<sup>23</sup>). Using the SKY92 classifier, 13% of patients were high risk (HR) (3-year OS rates: standard risk [SR], 70%; HR, 28%; P,.001). Combining SKY92 with R-ISS resulted in 3 risk groups: SKY-RISS I (SKY-SR 1 R-ISS-I; 15%), SKY-RISS III (SKY-HR 1 R-ISS-II/III; 11%), and SKY-RISS II (all other patients; 74%). The 3-year OS rates for SKY-RISS I, II, and III are 88%, 66%, and 26%, respectively (P 5 6 3 10<sup>27</sup>). The SKY-RISS model was validated in older patients from the CoMMpass dataset. Moreover, SKY-RISS demonstrated predictive potential: HR patients appeared to benefit from MPR-R over MPT-T (median OS, 55 and 14 months, respectively). Combined, SKY92 and R-ISS classify patients more accurately. Additionally, benefit was observed for MPR-R over MPT-T in SKY92-RISS HR patients only.</p>}},
author = {{Kuiper, Rowan and Zweegman, Sonja and van Duin, Mark and van Vliet, Martin H. and van Beers, Erik H. and Dumee, Belinda and Vermeulen, Michael and Koenders, Jasper and van der Holt, Bronno and Visser-Wisselaar, Heleen and Hansson, Markus and van der Velden, Annette W.G. and Berna Beverloo, H. and Stevens-Kroef, Marian and Levin, Mark David and Broijl, Annemiek and Waage, Anders and Sonneveld, Pieter}},
issn = {{2473-9529}},
language = {{eng}},
number = {{24}},
pages = {{6298--6309}},
publisher = {{American Society of Hematology}},
series = {{Blood Advances}},
title = {{Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma : The HOVON-87/NMSG-18 trial}},
url = {{http://dx.doi.org/10.1182/bloodadvances.2020002838}},
doi = {{10.1182/bloodadvances.2020002838}},
volume = {{4}},
year = {{2020}},
}