17 juli 2023: Bron:  2023 Apr 6; 141(14): 1666–1674. Published online 2022 Dec 27

Wetenschappers in de VK hebben voor de eerste keer een studie gedaan, de OPTIMUM studie,  waarbij patiënten met nieuwe diagnose van Multiple Myeloma, voor en na een autologe stamceltransplantatie werden behandeld op basis van een genentest om te bepalen of de patiënt in de HR = hoog risico groep zit of niet.

De patiënten die in de hoog risicogroep zaten kregen zowel voor als na de autologe stamceltransplantatie een behandeling met daratumumab, cyclofosfamide, bortezomib, lenalidomide en dexamethason (Dara-CVRd).

Om een vergelijking te hebben werden de resultaten vergeleken met die van patiënten met UHiR NDMM uit de Myeloma XI (MyeXI)-studie.

Bij de follow-up na 30 maanden waren de progressievrije overlevingspercentages respectievelijk 77,0% en 39,8% voor OPTIMUM en MyeXI, en de totale overlevingspercentages waren respectievelijk 83,5% versus 73,5%. Bijwerkingen waren vergelijkbaar tussen beide groepen. 

Hier een grafiek uit de Myeloma XI (MyeXI)-studie waarbij de hoog risicopatiënten dus zijn vergeleken:

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Het doen van een genentest al bij de eerste diagnose bewijst dus dat dit bij deze patientengroepen gevolgen heeft voor de uiteindelijke resultaten van de behandeling. 

Hier respectievelijk het studierapport van de OPTIMUM studie en die van de Myeloma XI (MyeXI)-studie:


Purpose: The multicenter OPTIMUM (MUKnine) phase II trial investigated daratumumab, low-dose cyclophosphamide, lenalidomide, bortezomib, and dexamethasone (Dara-CVRd) before and after autologous stem-cell transplant (ASCT) in newly diagnosed patients with molecularly defined ultra-high-risk (UHiR) multiple myeloma (NDMM) or plasma cell leukemia (PCL). To provide clinical context, progression-free survival (PFS) and overall survival (OS) were referenced to contemporaneous outcomes seen in patients with UHiR NDMM treated in the recent Myeloma XI (MyeXI) trial.

Methods: Transplant-eligible all-comers NDMM patients were profiled for UHiR disease, defined by presence of ≥2 genetic risk markers t(4;14)/t(14;16)/t(14;20), del(1p), gain(1q), and del(17p), and/or SKY92 gene expression risk signature. Patients with UHiR MM/PCL were offered treatment with Dara-CVRd induction, V-augmented ASCT, extended Dara-VR(d) consolidation, and Dara-R maintenance. UHiR patients treated in MyeXI with carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide, or lenalidomide, dexamethasone, and cyclophosphamide, ASCT, and R maintenance or observation were identified by mirrored molecular screening. OPTIMUM PFS at 18 months (PFS18m) was compared against MyeXI using a Bayesian framework, and patients were followed up to the end of consolidation for PFS and OS.

Results: Of 412 screened NDMM OPTIMUM patients, 103 were identified as UHiR or PCL and subsequently treated on trial with Dara-CVRd; 117 MyeXI patients identified as UHiR formed the external comparator arm, with comparable clinical and molecular characteristics to OPTIMUM. Comparison of PFS18m per Bayesian framework resulted in a 99.5% chance of OPTIMUM being superior to MyeXI. At 30 months' follow-up, PFS was 77% for OPTIMUM versus 39.8% for MyeXI, and OS 83.5% versus 73.5%, respectively. Extended post-ASCT Dara-VRd consolidation therapy was highly deliverable, with limited toxicity.

Conclusion: Our results suggest that Dara-CVRd induction and extended post-ASCT Dara-VRd consolidation markedly improve PFS for UHiR NDMM patients over conventional management, supporting further evaluation of this strategy.

Trial registration: 


  • Mina R, Musto P, Rota-Scalabrini D, Paris L, Gamberi B, Palmas A, Aquino S, de Fabritiis P, Giuliani N, De Rosa L, Gozzetti A, Cellini C, Bertamini L, Capra A, Oddolo D, Vincelli ID, Ronconi S, Pavone V, Pescosta N, Cea M, Fioritoni F, Ballanti S, Grasso M, Zamagni E, Belotti A, Boccadoro M, Gay F.Lancet Oncol. 2023 Jan;24(1):64-76. doi: 10.1016/S1470-2045(22)00693-3. Epub 2022 Dec 14.PMID: 36528035 Clinical Trial.
  • Gay F, Musto P, Rota-Scalabrini D, Bertamini L, Belotti A, Galli M, Offidani M, Zamagni E, Ledda A, Grasso M, Ballanti S, Spadano A, Cea M, Patriarca F, D'Agostino M, Capra A, Giuliani N, de Fabritiis P, Aquino S, Palmas A, Gamberi B, Zambello R, Petrucci MT, Corradini P, Cavo M, Boccadoro M.Lancet Oncol. 2021 Dec;22(12):1705-1720. doi: 10.1016/S1470-2045(21)00535-0. Epub 2021 Nov 11.PMID: 34774221 Clinical Trial.
  • Tanimura A, Hirai R, Nakamura M, Takeshita M, Togano T, Sekine R, Hagiwara S, Miwa A.Gan To Kagaku Ryoho. 2020 May;47(5):789-796.PMID: 32408321
  • Offidani M, Corvatta L, Morè S, Nappi D, Martinelli G, Olivieri A, Cerchione C.Front Oncol. 2021 Feb 17;10:624661. doi: 10.3389/fonc.2020.624661. eCollection 2020.PMID: 33680948 Free PMC article. Review.
  • Rajkumar SV.Am J Hematol. 2020 May;95(5):548-567. doi: 10.1002/ajh.25791.PMID: 32212178 Review.

Associated data

En de Myeloma XI (MyeXI)-studie:

2023 Apr 6; 141(14): 1666–1674.
Published online 2022 Dec 27. 
PMCID: PMC10113174

Optimizing the value of lenalidomide maintenance by extended genetic profiling: an analysis of 556 patients in the Myeloma XI trial

Visual Abstract

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Prediction of individual patient benefit from lenalidomide (Len) maintenance after autologous stem cell transplant (ASCT) remains challenging. Here, we investigated extended molecular profiling for outcome prediction in patients in the National Cancer Research Institute Myeloma XI (MyXI) trial. Patients in the MyXI trial randomized to Len maintenance or observation after ASCT were genetically profiled for t(4;14), t(14;16), t(14;20), del(1p), gain(1q), and del(17p) and co-occurrence of risk markers was computed. Progression-free survival (PFS), subsequent progression (PFS2), and overall survival (OS) were calculated from maintenance randomization, and groups were compared using Cox proportional hazards regression. Of 556 patients, 17% with double-hit multiple myeloma (MM) (≥2 risk markers), 32% with single-hit (1 risk marker), and 51% without risk markers were analyzed. Single-hit MM derived the highest PFS benefit from Len maintenance, specifically, isolated del(1p), del(17p), and t(4;14), with ∼40-fold, 10-fold, and sevenfold reduced risk of progression or death (PFS), respectively, compared with observation. This benefit translated into improved PFS2 and OS for this group of patients compared with observation; median PFS was 10.9 vs 57.3 months for observation vs Len maintenance. Patients with isolated gain(1q) derived no benefit, and double-hit MM limited benefit (regardless or risk lesions involved) from Len maintenance. Extended genetic profiling identifies patients deriving exceptional benefit from Len maintenance and should be considered for newly diagnosed patients to support management discussions along their treatment pathway. This trial was registered at www.isrctn.com/ISRCTN49407852 as # ISRCTN49407852.

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