Expression-linked and R-ISS-Adapted Stratification for first line therapy in multiple myeloma patients (ELIAS)

Leitner, T.; Hoegner, M.; Bassermann, F.; Weisel, K.; Kroenke, J.; Nogai, A.; Knop, S.; Rasche, R.; van Heteren, P.; Shumilov, E.; Koch, R.; Koenig, I. R.; Klinge, K.; Horn, K.; von Bubnoff, N. C. C.; Khandanpour, C.

Zusammenfassung

Newly diagnosed transplant-eligible patients with multiple myeloma (MM) generally undergo several cycles of induction, followed by one or two cycles of high-dose melphalan (HDM) and autologous stem cell transfusion (ASCT). In MM patients, HDM improves overall and progression-free survival (OS and PFS). But exposure to melphalan increases the risk of secondary malignancies and might render residual myeloma cells into more aggressive clones, accelerating relapse. It remains to be answered, whether also low risk patients have an additional benet from HDM therapy compared to less toxic regimen. In this multicenter phase II, interventional, controlled, randomized, prospective, and open-label study we propose a personalized approach to evaluate whether patients with a low-risk prole (R-ISS stage I, characterized by low tumor burden and absence of adverse cytogenetic ndings or elevated LDH) and with a gene expression prole (using the SKY92 GEP assay), indicating a standard risk of relapse, might be suciently treated with intensied consolidation courses without upfront HDM chemotherapy. e study investigates the impact and the risk-benet ratio of three cycles of isatuximab, bortezomib, lenalidomide und dexamethasone (I-VRD), stem cell apheresis and high-dose melphalan followed by ASCT and an isatuximab and lenalidomide based maintenance therapy as the standard of care control treatment group compared to the experimental group treated with 3 cycles of I-VRD, stem cell apheresis and three subsequent consolidation cycles of I-VRD followed by an isatuximab and lenalidomide based maintenance therapy. All eligible subjects will start with an I-VRD induction treatment. Aer 3 cycles all patients reaching at least a partial remission will be randomized to standard of care treatment or three more cycles of I-VRD. e primary objective is to show non-inferiority of the experimental arm compared to the control arm with standard of care regarding the rate of patients with minimal residual disease (MRD) negativity combined with at least a complete remission response according to IMWG criteria at week 40 aer start of induction therapy (18 weeks aer randomization). Furthermore, we aim to detect possible dierences in MRD negativity at specic points of time and to characterize both arms with respect to OS and PFS since randomization, PFS during second-line treatment since relapse, time to next treatment, and overall response rate. Disclosure: eo Leitner: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Marion Högner: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Florian Bassermann: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Katja Weisel: Advisory Role:Sano: Consulting Fees, Honoraria:Sano: Honoraria (lectures, presentation), Financing of Scientic Research:Sano: Research grant to institution; Sano: is study is nancially supported by Sano; Jan Krönke: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Axel Nogai: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Stefan Knop: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Rasche Rasche: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Pearl van Heteren: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Evgenii Shumilov: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Raphael Koch: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Inke R. König: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Kathrin Klinge: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Kay Horn: Financing of Scientic Research:Sano: is study is nancially supported by Sano; Nikolas Christian Cornelius von Bubno: Financing of Scientic Research:SSano: is study is nancially supported by Sano; Cyrus Khandanpour: Financing of Scientic Research:Sano: is study is nancially supported by Sano.