Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma: the HOVON-87/NMSG-18 trial

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 subs...

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Veröffentlicht in:Blood advances 2020-12, Vol.4 (24), p.6298-6309
Hauptverfasser: 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, van der Velden, Annette W.G., Beverloo, H. Berna, Stevens-Kroef, Marian, Levin, Mark-David, Broijl, Annemiek, Waage, Anders, Sonneveld, Pieter
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Sprache:eng
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Zusammenfassung: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 = 8 × 10−3). 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 + R-ISS-I; 15%), SKY-RISS III (SKY-HR + 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 = 6 × 10−7). 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. •Combining SKY92 with R-ISS results in a superior prognostic marker compared with either marker separately.•SKY-RISS acts as an immunomodulatory agent predictor. A benefit of MPR-R over MPT-T was seen for HR patients only. [Display omitted]
ISSN:2473-9529
2473-9537
DOI:10.1182/bloodadvances.2020002838