Prommis Trial Prospectively Demonstrates the Efficacy of SKY92 Risk Stratification in Newly Diagnosed Multiple Myeloma Patients
Introduction: Multiple myeloma (MM) is a complex hematologic malignancy characterized by genetic instability, variable survival rates, and diverse treatment responses. SKY92 gene expression profiling (GEP) is a valuable tool in risk stratifying patients into high-risk and standard-risk groups for pr...
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| Veröffentlicht in: | Blood 2023-11, Vol.142 (Supplement 1), p.3386-3386 |
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| creator | Biran, Noa Dhakal, Binod Niesvizky, Ruben Lentzsch, Suzanne McKay, John T. Vesole, David H. Nooka, Ajay K. Paul, Barry Hari, Parameswaran N. Stork-Sloots, Lisette D'Ambrosi, Silvia Kuiper, Rowan van Vliet, Martin Siegel, David S. Usmani, Saad Z van Rhee, Frits |
| description | Introduction: Multiple myeloma (MM) is a complex hematologic malignancy characterized by genetic instability, variable survival rates, and diverse treatment responses. SKY92 gene expression profiling (GEP) is a valuable tool in risk stratifying patients into high-risk and standard-risk groups for progression and survival. The PRospective Observational Multiple Myeloma Impact Study (PROMMIS; NCT02911571) trial, a prospective US multicenter study, was designed to validate the prognostic performance of SKY92 through real-world data.
Methods: The GEP of 251 newly diagnosed MM patients was assessed using the SKY92 assay (SkylineDx, San Diego), which involved analyzing RNA extracted from CD138-positive plasma cells (≥80% purity) isolated through immunomagnetic separation. The test was performed at the enrolling institute, or by sending the samples into a central lab. The standard method for risk stratification by R-ISS stage was integrated with SKY92 into three distinct groups: Low-Risk (LR), defined by SKY92 standard-risk (SR) combined with R-ISS I; Intermediate Risk (IR), as SKY92 SR with R-ISS II/III, or SKY92 high-risk with R-ISS I; and High-Risk as SKY92 high-risk with R-ISS II/III. Progression-free survival (PFS) and overall survival (OS) were available for 221 patients, measured from the date of diagnosis of the patients. The median follow-up at the time of analysis is 38 months. Survival analyses were performed using Cox proportional hazards model.
Results: Upon analysis, 179 patients (71.3%) were classified as SKY92 standard-risk, and 72 patients (28.7%) as SKY92 high-risk. Notably, the percentage of high-risk patients in this study was slightly higher than that observed in previous retrospective analyses (15-25%).
Furthermore, the survival analysis revealed significant differences in both PFS (HR: 2.1, 95%CI 1.4-3.1, p |
| doi_str_mv | 10.1182/blood-2023-180761 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1182_blood_2023_180761</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497123099883</els_id><sourcerecordid>S0006497123099883</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1371-6d0284585f351cd54037619bd36e9cbd86adad21a5bc47fd3e587d28867dc1413</originalsourceid><addsrcrecordid>eNp9kM1OwzAQhC0EEqXwANz8AgH_xIkrTqiUH9FCRcuBk-XYGzAkcWWHopx4dRLKmdNqtTOrmQ-hU0rOKJXsvKi8twkjjCdUkjyje2hEBZMJIYzsoxEhJEvSSU4P0VGM74TQlDMxQt_L4OvaRbwOTle43-IGTOu2UHX4CmrfxDboFiJu3wDPytIZbTrsS7y6f5kw_OTiB14NEjecWucb7Br8AF-D3-nXxkewePFZtW5TAV50UPla42UvhaaNx-ig1FWEk785Rs_Xs_X0Npk_3txNL-eJoTynSWYJk6mQouSCGitSwvuOk8LyDCamsDLTVltGtShMmpeWg5C5ZVJmuTU0pXyM6O6v6RvGAKXaBFfr0ClK1EBQ_RJUA0G1I9h7LnYe6INtHQQVTR_agHWhZ6Ssd_-4fwCvm3r1</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Prommis Trial Prospectively Demonstrates the Efficacy of SKY92 Risk Stratification in Newly Diagnosed Multiple Myeloma Patients</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Biran, Noa ; Dhakal, Binod ; Niesvizky, Ruben ; Lentzsch, Suzanne ; McKay, John T. ; Vesole, David H. ; Nooka, Ajay K. ; Paul, Barry ; Hari, Parameswaran N. ; Stork-Sloots, Lisette ; D'Ambrosi, Silvia ; Kuiper, Rowan ; van Vliet, Martin ; Siegel, David S. ; Usmani, Saad Z ; van Rhee, Frits</creator><creatorcontrib>Biran, Noa ; Dhakal, Binod ; Niesvizky, Ruben ; Lentzsch, Suzanne ; McKay, John T. ; Vesole, David H. ; Nooka, Ajay K. ; Paul, Barry ; Hari, Parameswaran N. ; Stork-Sloots, Lisette ; D'Ambrosi, Silvia ; Kuiper, Rowan ; van Vliet, Martin ; Siegel, David S. ; Usmani, Saad Z ; van Rhee, Frits</creatorcontrib><description>Introduction: Multiple myeloma (MM) is a complex hematologic malignancy characterized by genetic instability, variable survival rates, and diverse treatment responses. SKY92 gene expression profiling (GEP) is a valuable tool in risk stratifying patients into high-risk and standard-risk groups for progression and survival. The PRospective Observational Multiple Myeloma Impact Study (PROMMIS; NCT02911571) trial, a prospective US multicenter study, was designed to validate the prognostic performance of SKY92 through real-world data.
Methods: The GEP of 251 newly diagnosed MM patients was assessed using the SKY92 assay (SkylineDx, San Diego), which involved analyzing RNA extracted from CD138-positive plasma cells (≥80% purity) isolated through immunomagnetic separation. The test was performed at the enrolling institute, or by sending the samples into a central lab. The standard method for risk stratification by R-ISS stage was integrated with SKY92 into three distinct groups: Low-Risk (LR), defined by SKY92 standard-risk (SR) combined with R-ISS I; Intermediate Risk (IR), as SKY92 SR with R-ISS II/III, or SKY92 high-risk with R-ISS I; and High-Risk as SKY92 high-risk with R-ISS II/III. Progression-free survival (PFS) and overall survival (OS) were available for 221 patients, measured from the date of diagnosis of the patients. The median follow-up at the time of analysis is 38 months. Survival analyses were performed using Cox proportional hazards model.
Results: Upon analysis, 179 patients (71.3%) were classified as SKY92 standard-risk, and 72 patients (28.7%) as SKY92 high-risk. Notably, the percentage of high-risk patients in this study was slightly higher than that observed in previous retrospective analyses (15-25%).
Furthermore, the survival analysis revealed significant differences in both PFS (HR: 2.1, 95%CI 1.4-3.1, p<0.001) and OS (HR: 3.7, 95%CI 1.8-7.6, p<0.001) between the two risk categories. The median PFS from the time of the diagnosis for SKY92 standard-risk patients was 50 months, whereas for SKY92 high-risk patients, it was 26 months. The median OS was not reached within the 60-month timeframe for both the standard- and high-risk groups.
R-ISS could be determined for 204 patients (81%), of which 29.9% (n=61) were classified as stage I, 59.3% (n=121) as stage II, and 10.8% (n=22) as stage III. We integrated R-ISS staging with SKY92 classification for these patients. The combination of these two classification systems yielded the following stratification ( Figure 1): LR n=53 (27%), IR n=96 (47%), and High-Risk n=55 (26%). Consistent with previous studies, R-ISS and SKY92 hold independent prognostic value: in particular, we found that this combined classification method identified a higher number of patients as high-risk compared to the R-ISS annotation (55 [27%] vs. 22 [11%]). The high-risk group exhibited significantly shorter OS and PFS compared to the LR group (OS: HR:18.7, 95% CI 2.5-140, p=0.004 and PFS: HR:2.6, 95% CI 1.4-4.7, p=0.002).
Conclusions: This study represents the first US-based multicenter prospective evaluation of the GEP SKY92 in a real-world clinical setting. The results obtained align with the retrospective validations of SKY92, further confirming its reliability as a prognostic marker for MM patients. In addition, we observed that the SKY92 is able to identify a higher number of high-risk patients, with significantly shorter PFS and OS, compared to the conventional R-ISS staging system.
Figure 1: PFS and OS based on SKY92+R-ISS risk classification
Biran:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; abbvie: Honoraria; Genomic testing cooperative: Divested equity in a private or publicly-traded company in the past 24 months; GSK: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Other: spouse of employee. Dhakal:Janssen, Karyopharm, GSK, Arcellx, GSK, Sanofi, Genentech, Pfizer: Consultancy, Honoraria, Speakers Bureau. Lentzsch:Janssen: Membership on an entity's Board of Directors or advisory committees; Caelum Biosciences: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: January 1, 2041; Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria; Pfizer: Consultancy; Oncopeptide: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Clinical Care Options: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. McKay:BMS: Consultancy. Nooka:Aduro Biotech, Amgen, Arch Oncology, Bristol Myers Squibb, Cellectis, Genentech, GlaxoSmithKline, Janssen, Karyopharm, Kite Pharma, Merck, Pfizer, Takeda: Honoraria, Research Funding; Adaptive Biotechnologies, Amgen, BeyondSpring, Bristol Myers Squibb, Cellectar Biosciences, GlaxoSmithKline, Janssen, Karyopharm, Oncopeptides, ONK therapeutics, Pfizer, Sanofi, Secura Bio, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Paul:Janssen: Membership on an entity's Board of Directors or advisory committees. D'Ambrosi:SkylineDx: Current Employment. Kuiper:SkylineDx: Current Employment. van Vliet:SkylineDx: Current Employment. Siegel:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celularity Scientific: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Usmani:GSK: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Moderna: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; K36 Therapeutics: Membership on an entity's Board of Directors or advisory committees; SecuraBio: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; SkylineDX: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; EdoPharma: Membership on an entity's Board of Directors or advisory committees; TeneoBio: Membership on an entity's Board of Directors or advisory committees; Array Biopharma: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding. van Rhee:Janssen Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; GlaxoSmithKline: Consultancy; Adicet Bio: Consultancy; EUSA Bio: Consultancy.
[Display omitted]</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2023-180761</identifier><language>eng</language><publisher>Elsevier Inc</publisher><ispartof>Blood, 2023-11, Vol.142 (Supplement 1), p.3386-3386</ispartof><rights>2023 The American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Biran, Noa</creatorcontrib><creatorcontrib>Dhakal, Binod</creatorcontrib><creatorcontrib>Niesvizky, Ruben</creatorcontrib><creatorcontrib>Lentzsch, Suzanne</creatorcontrib><creatorcontrib>McKay, John T.</creatorcontrib><creatorcontrib>Vesole, David H.</creatorcontrib><creatorcontrib>Nooka, Ajay K.</creatorcontrib><creatorcontrib>Paul, Barry</creatorcontrib><creatorcontrib>Hari, Parameswaran N.</creatorcontrib><creatorcontrib>Stork-Sloots, Lisette</creatorcontrib><creatorcontrib>D'Ambrosi, Silvia</creatorcontrib><creatorcontrib>Kuiper, Rowan</creatorcontrib><creatorcontrib>van Vliet, Martin</creatorcontrib><creatorcontrib>Siegel, David S.</creatorcontrib><creatorcontrib>Usmani, Saad Z</creatorcontrib><creatorcontrib>van Rhee, Frits</creatorcontrib><title>Prommis Trial Prospectively Demonstrates the Efficacy of SKY92 Risk Stratification in Newly Diagnosed Multiple Myeloma Patients</title><title>Blood</title><description>Introduction: Multiple myeloma (MM) is a complex hematologic malignancy characterized by genetic instability, variable survival rates, and diverse treatment responses. SKY92 gene expression profiling (GEP) is a valuable tool in risk stratifying patients into high-risk and standard-risk groups for progression and survival. The PRospective Observational Multiple Myeloma Impact Study (PROMMIS; NCT02911571) trial, a prospective US multicenter study, was designed to validate the prognostic performance of SKY92 through real-world data.
Methods: The GEP of 251 newly diagnosed MM patients was assessed using the SKY92 assay (SkylineDx, San Diego), which involved analyzing RNA extracted from CD138-positive plasma cells (≥80% purity) isolated through immunomagnetic separation. The test was performed at the enrolling institute, or by sending the samples into a central lab. The standard method for risk stratification by R-ISS stage was integrated with SKY92 into three distinct groups: Low-Risk (LR), defined by SKY92 standard-risk (SR) combined with R-ISS I; Intermediate Risk (IR), as SKY92 SR with R-ISS II/III, or SKY92 high-risk with R-ISS I; and High-Risk as SKY92 high-risk with R-ISS II/III. Progression-free survival (PFS) and overall survival (OS) were available for 221 patients, measured from the date of diagnosis of the patients. The median follow-up at the time of analysis is 38 months. Survival analyses were performed using Cox proportional hazards model.
Results: Upon analysis, 179 patients (71.3%) were classified as SKY92 standard-risk, and 72 patients (28.7%) as SKY92 high-risk. Notably, the percentage of high-risk patients in this study was slightly higher than that observed in previous retrospective analyses (15-25%).
Furthermore, the survival analysis revealed significant differences in both PFS (HR: 2.1, 95%CI 1.4-3.1, p<0.001) and OS (HR: 3.7, 95%CI 1.8-7.6, p<0.001) between the two risk categories. The median PFS from the time of the diagnosis for SKY92 standard-risk patients was 50 months, whereas for SKY92 high-risk patients, it was 26 months. The median OS was not reached within the 60-month timeframe for both the standard- and high-risk groups.
R-ISS could be determined for 204 patients (81%), of which 29.9% (n=61) were classified as stage I, 59.3% (n=121) as stage II, and 10.8% (n=22) as stage III. We integrated R-ISS staging with SKY92 classification for these patients. The combination of these two classification systems yielded the following stratification ( Figure 1): LR n=53 (27%), IR n=96 (47%), and High-Risk n=55 (26%). Consistent with previous studies, R-ISS and SKY92 hold independent prognostic value: in particular, we found that this combined classification method identified a higher number of patients as high-risk compared to the R-ISS annotation (55 [27%] vs. 22 [11%]). The high-risk group exhibited significantly shorter OS and PFS compared to the LR group (OS: HR:18.7, 95% CI 2.5-140, p=0.004 and PFS: HR:2.6, 95% CI 1.4-4.7, p=0.002).
Conclusions: This study represents the first US-based multicenter prospective evaluation of the GEP SKY92 in a real-world clinical setting. The results obtained align with the retrospective validations of SKY92, further confirming its reliability as a prognostic marker for MM patients. In addition, we observed that the SKY92 is able to identify a higher number of high-risk patients, with significantly shorter PFS and OS, compared to the conventional R-ISS staging system.
Figure 1: PFS and OS based on SKY92+R-ISS risk classification
Biran:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; abbvie: Honoraria; Genomic testing cooperative: Divested equity in a private or publicly-traded company in the past 24 months; GSK: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Other: spouse of employee. Dhakal:Janssen, Karyopharm, GSK, Arcellx, GSK, Sanofi, Genentech, Pfizer: Consultancy, Honoraria, Speakers Bureau. Lentzsch:Janssen: Membership on an entity's Board of Directors or advisory committees; Caelum Biosciences: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: January 1, 2041; Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria; Pfizer: Consultancy; Oncopeptide: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Clinical Care Options: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. McKay:BMS: Consultancy. Nooka:Aduro Biotech, Amgen, Arch Oncology, Bristol Myers Squibb, Cellectis, Genentech, GlaxoSmithKline, Janssen, Karyopharm, Kite Pharma, Merck, Pfizer, Takeda: Honoraria, Research Funding; Adaptive Biotechnologies, Amgen, BeyondSpring, Bristol Myers Squibb, Cellectar Biosciences, GlaxoSmithKline, Janssen, Karyopharm, Oncopeptides, ONK therapeutics, Pfizer, Sanofi, Secura Bio, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Paul:Janssen: Membership on an entity's Board of Directors or advisory committees. D'Ambrosi:SkylineDx: Current Employment. Kuiper:SkylineDx: Current Employment. van Vliet:SkylineDx: Current Employment. Siegel:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celularity Scientific: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Usmani:GSK: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Moderna: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; K36 Therapeutics: Membership on an entity's Board of Directors or advisory committees; SecuraBio: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; SkylineDX: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; EdoPharma: Membership on an entity's Board of Directors or advisory committees; TeneoBio: Membership on an entity's Board of Directors or advisory committees; Array Biopharma: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding. van Rhee:Janssen Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; GlaxoSmithKline: Consultancy; Adicet Bio: Consultancy; EUSA Bio: Consultancy.
[Display omitted]</description><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kM1OwzAQhC0EEqXwANz8AgH_xIkrTqiUH9FCRcuBk-XYGzAkcWWHopx4dRLKmdNqtTOrmQ-hU0rOKJXsvKi8twkjjCdUkjyje2hEBZMJIYzsoxEhJEvSSU4P0VGM74TQlDMxQt_L4OvaRbwOTle43-IGTOu2UHX4CmrfxDboFiJu3wDPytIZbTrsS7y6f5kw_OTiB14NEjecWucb7Br8AF-D3-nXxkewePFZtW5TAV50UPla42UvhaaNx-ig1FWEk785Rs_Xs_X0Npk_3txNL-eJoTynSWYJk6mQouSCGitSwvuOk8LyDCamsDLTVltGtShMmpeWg5C5ZVJmuTU0pXyM6O6v6RvGAKXaBFfr0ClK1EBQ_RJUA0G1I9h7LnYe6INtHQQVTR_agHWhZ6Ssd_-4fwCvm3r1</recordid><startdate>20231102</startdate><enddate>20231102</enddate><creator>Biran, Noa</creator><creator>Dhakal, Binod</creator><creator>Niesvizky, Ruben</creator><creator>Lentzsch, Suzanne</creator><creator>McKay, John T.</creator><creator>Vesole, David H.</creator><creator>Nooka, Ajay K.</creator><creator>Paul, Barry</creator><creator>Hari, Parameswaran N.</creator><creator>Stork-Sloots, Lisette</creator><creator>D'Ambrosi, Silvia</creator><creator>Kuiper, Rowan</creator><creator>van Vliet, Martin</creator><creator>Siegel, David S.</creator><creator>Usmani, Saad Z</creator><creator>van Rhee, Frits</creator><general>Elsevier Inc</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20231102</creationdate><title>Prommis Trial Prospectively Demonstrates the Efficacy of SKY92 Risk Stratification in Newly Diagnosed Multiple Myeloma Patients</title><author>Biran, Noa ; Dhakal, Binod ; Niesvizky, Ruben ; Lentzsch, Suzanne ; McKay, John T. ; Vesole, David H. ; Nooka, Ajay K. ; Paul, Barry ; Hari, Parameswaran N. ; Stork-Sloots, Lisette ; D'Ambrosi, Silvia ; Kuiper, Rowan ; van Vliet, Martin ; Siegel, David S. ; Usmani, Saad Z ; van Rhee, Frits</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1371-6d0284585f351cd54037619bd36e9cbd86adad21a5bc47fd3e587d28867dc1413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Biran, Noa</creatorcontrib><creatorcontrib>Dhakal, Binod</creatorcontrib><creatorcontrib>Niesvizky, Ruben</creatorcontrib><creatorcontrib>Lentzsch, Suzanne</creatorcontrib><creatorcontrib>McKay, John T.</creatorcontrib><creatorcontrib>Vesole, David H.</creatorcontrib><creatorcontrib>Nooka, Ajay K.</creatorcontrib><creatorcontrib>Paul, Barry</creatorcontrib><creatorcontrib>Hari, Parameswaran N.</creatorcontrib><creatorcontrib>Stork-Sloots, Lisette</creatorcontrib><creatorcontrib>D'Ambrosi, Silvia</creatorcontrib><creatorcontrib>Kuiper, Rowan</creatorcontrib><creatorcontrib>van Vliet, Martin</creatorcontrib><creatorcontrib>Siegel, David S.</creatorcontrib><creatorcontrib>Usmani, Saad Z</creatorcontrib><creatorcontrib>van Rhee, Frits</creatorcontrib><collection>CrossRef</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Biran, Noa</au><au>Dhakal, Binod</au><au>Niesvizky, Ruben</au><au>Lentzsch, Suzanne</au><au>McKay, John T.</au><au>Vesole, David H.</au><au>Nooka, Ajay K.</au><au>Paul, Barry</au><au>Hari, Parameswaran N.</au><au>Stork-Sloots, Lisette</au><au>D'Ambrosi, Silvia</au><au>Kuiper, Rowan</au><au>van Vliet, Martin</au><au>Siegel, David S.</au><au>Usmani, Saad Z</au><au>van Rhee, Frits</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prommis Trial Prospectively Demonstrates the Efficacy of SKY92 Risk Stratification in Newly Diagnosed Multiple Myeloma Patients</atitle><jtitle>Blood</jtitle><date>2023-11-02</date><risdate>2023</risdate><volume>142</volume><issue>Supplement 1</issue><spage>3386</spage><epage>3386</epage><pages>3386-3386</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Introduction: Multiple myeloma (MM) is a complex hematologic malignancy characterized by genetic instability, variable survival rates, and diverse treatment responses. SKY92 gene expression profiling (GEP) is a valuable tool in risk stratifying patients into high-risk and standard-risk groups for progression and survival. The PRospective Observational Multiple Myeloma Impact Study (PROMMIS; NCT02911571) trial, a prospective US multicenter study, was designed to validate the prognostic performance of SKY92 through real-world data.
Methods: The GEP of 251 newly diagnosed MM patients was assessed using the SKY92 assay (SkylineDx, San Diego), which involved analyzing RNA extracted from CD138-positive plasma cells (≥80% purity) isolated through immunomagnetic separation. The test was performed at the enrolling institute, or by sending the samples into a central lab. The standard method for risk stratification by R-ISS stage was integrated with SKY92 into three distinct groups: Low-Risk (LR), defined by SKY92 standard-risk (SR) combined with R-ISS I; Intermediate Risk (IR), as SKY92 SR with R-ISS II/III, or SKY92 high-risk with R-ISS I; and High-Risk as SKY92 high-risk with R-ISS II/III. Progression-free survival (PFS) and overall survival (OS) were available for 221 patients, measured from the date of diagnosis of the patients. The median follow-up at the time of analysis is 38 months. Survival analyses were performed using Cox proportional hazards model.
Results: Upon analysis, 179 patients (71.3%) were classified as SKY92 standard-risk, and 72 patients (28.7%) as SKY92 high-risk. Notably, the percentage of high-risk patients in this study was slightly higher than that observed in previous retrospective analyses (15-25%).
Furthermore, the survival analysis revealed significant differences in both PFS (HR: 2.1, 95%CI 1.4-3.1, p<0.001) and OS (HR: 3.7, 95%CI 1.8-7.6, p<0.001) between the two risk categories. The median PFS from the time of the diagnosis for SKY92 standard-risk patients was 50 months, whereas for SKY92 high-risk patients, it was 26 months. The median OS was not reached within the 60-month timeframe for both the standard- and high-risk groups.
R-ISS could be determined for 204 patients (81%), of which 29.9% (n=61) were classified as stage I, 59.3% (n=121) as stage II, and 10.8% (n=22) as stage III. We integrated R-ISS staging with SKY92 classification for these patients. The combination of these two classification systems yielded the following stratification ( Figure 1): LR n=53 (27%), IR n=96 (47%), and High-Risk n=55 (26%). Consistent with previous studies, R-ISS and SKY92 hold independent prognostic value: in particular, we found that this combined classification method identified a higher number of patients as high-risk compared to the R-ISS annotation (55 [27%] vs. 22 [11%]). The high-risk group exhibited significantly shorter OS and PFS compared to the LR group (OS: HR:18.7, 95% CI 2.5-140, p=0.004 and PFS: HR:2.6, 95% CI 1.4-4.7, p=0.002).
Conclusions: This study represents the first US-based multicenter prospective evaluation of the GEP SKY92 in a real-world clinical setting. The results obtained align with the retrospective validations of SKY92, further confirming its reliability as a prognostic marker for MM patients. In addition, we observed that the SKY92 is able to identify a higher number of high-risk patients, with significantly shorter PFS and OS, compared to the conventional R-ISS staging system.
Figure 1: PFS and OS based on SKY92+R-ISS risk classification
Biran:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; abbvie: Honoraria; Genomic testing cooperative: Divested equity in a private or publicly-traded company in the past 24 months; GSK: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Other: spouse of employee. Dhakal:Janssen, Karyopharm, GSK, Arcellx, GSK, Sanofi, Genentech, Pfizer: Consultancy, Honoraria, Speakers Bureau. Lentzsch:Janssen: Membership on an entity's Board of Directors or advisory committees; Caelum Biosciences: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: January 1, 2041; Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria; Pfizer: Consultancy; Oncopeptide: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Clinical Care Options: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. McKay:BMS: Consultancy. Nooka:Aduro Biotech, Amgen, Arch Oncology, Bristol Myers Squibb, Cellectis, Genentech, GlaxoSmithKline, Janssen, Karyopharm, Kite Pharma, Merck, Pfizer, Takeda: Honoraria, Research Funding; Adaptive Biotechnologies, Amgen, BeyondSpring, Bristol Myers Squibb, Cellectar Biosciences, GlaxoSmithKline, Janssen, Karyopharm, Oncopeptides, ONK therapeutics, Pfizer, Sanofi, Secura Bio, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Paul:Janssen: Membership on an entity's Board of Directors or advisory committees. D'Ambrosi:SkylineDx: Current Employment. Kuiper:SkylineDx: Current Employment. van Vliet:SkylineDx: Current Employment. Siegel:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celularity Scientific: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Usmani:GSK: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Moderna: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; K36 Therapeutics: Membership on an entity's Board of Directors or advisory committees; SecuraBio: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; SkylineDX: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; EdoPharma: Membership on an entity's Board of Directors or advisory committees; TeneoBio: Membership on an entity's Board of Directors or advisory committees; Array Biopharma: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding. van Rhee:Janssen Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; GlaxoSmithKline: Consultancy; Adicet Bio: Consultancy; EUSA Bio: Consultancy.
[Display omitted]</abstract><pub>Elsevier Inc</pub><doi>10.1182/blood-2023-180761</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| title | Prommis Trial Prospectively Demonstrates the Efficacy of SKY92 Risk Stratification in Newly Diagnosed Multiple Myeloma Patients |
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