Abstract
The MM5 trial aimed at demonstrating a progression-free survival (PFS) difference in continued vs. response-adapted (in case of complete response, CR) lenalidomide (LEN) maintenance therapy (MT) in newly diagnosed, transplant-eligible multiple myeloma (MM). Patients were equally randomized to receive induction therapy with PAd (bortezomib/doxorubicin/dexamethasone) or VCD (bortezomib/cyclophosphamide/dexamethasone), high-dose melphalan and autologous blood stem cell transplantation, and LEN consolidation, followed by either LEN MT for a fixed duration of 2 years (LEN-2Y) or until achievement of CR (LEN-CR, intention-to-treat population n = 502): arms A1:PAd + LEN-2Y (n = 125), B1:PAd + LEN-CR (n = 126), A2:VCD + LEN-2Y (n = 126), B2:VCD + LEN-CR (n = 125). In the LEN-CR group (B1 + B2), n = 88/17.5% patients did not start or discontinued LEN MT due to CR. There was no PFS (p = 0.60, primary endpoint) nor overall survival (OS) (p = 0.15) difference between the four study arms. On pooled LEN MT strategies, OS (hazard ratio, hazard ratio [HR] = 1.42, p = 0.03) but not PFS (HR = 1.15, p = 0.20) was shorter in LEN-CR (B1 + B2) vs. LEN-2Y (A1 + A2) groups. PFS was shortened on landmark analyses from the start of LEN MT in patients being in CR in the LEN-CR group (LEN-CR vs. LEN-2Y, HR = 1.84, p = 0.02). OS from first progression was shortened in the LEN-CR vs. LEN-2Y group (HR = 1.60, p = 0.01). LEN MT should be applied beyond CR for at least 2 years.
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Acknowledgements
The GMMG-MM5 trial was supported by Celgene, Janssen-Cilag, Chugai, and The Binding Site. The GMMG thanks the Koordinierungszentrum für Klinische Studien (KKS) Heidelberg for the support of the trial and data monitoring. The GMMG thanks all participating investigators and centers (Supplementary Material 3).
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Conception and design: HG, UB, CK and TH. Responsible statisticians: CK, TH and DT. Administrative support: HG, UB and SL. Provision of study materials or patients and/or collection, assembly and review of data: all authors. Data analysis and interpretation: HG, EKM, UB, MSR, TH, TD and CK. Writing of the first manuscript draft: EKM, HG, UB, CK and TH. Manuscript editing, discussion of trial data/results, and final writing: all authors. Final approval of manuscript: all authors.
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HG: honoraria: Amgen, BMS, Celgene, Chugai, Janssen, Novartis, Takeda; consulting or advisory role: Amgen, BMS, Celgene, Chugai, Janssen, Novartis, Takeda; speakers bureau: Amgen, BMS, Celgene, Janssen, Novartis, Takeda; research funding: Amgen, BMS, Celgene, Chugai, Janssen, Novartis, Takeda; travel, accomodations, expenses: BMS, Celgene, Janssen, Novartis, Takeda. EKM: honoraria: Janssen, Celgene, Takeda; consulting or advisory role: Janssen, Celgene, Takeda; research funding: Takeda; travel, accomodations, expenses: Janssen, Takeda, Celgene, Onyx, Mundipharma. JD: consulting or advisory role: Celgene; speakers bureau: Celgene; travel, accomodations, expenses: Celgene. CS: honoraria: BMS, Janssen, Celgene, Novartis, Amgen, Takeda; consulting or advisory role: BMS, Janssen, Celgene, Novartis, Amgen, Takeda; speakers bureau: Takeda; research funding: Takeda, Novartis; travel, accomodations, expenses: BMS, Janssen, Celgene, Novartis, Amgen, Takeda. KCW: honoraria: AMGEN, BMS, Celgene, Novartis, Janssen, Takeda; consulting or advisory role: AMGEN, BMS, Celgene, Juno, Janssen, Adaptive, Sanofi, Takeda; research funding: AMGEN, Celgene, Sanofi, Janssen; CK: no COI. UB: travel, accomodations, expenses: Sanofi TH: no COI. MMe: consulting or advisory role: Amgen, Takeda; research funding: Takeda; travel, accomodations, expenses: Celgen, AMGEN, Takeda, Abbvie, Janssen. MMu: honoraria: Janssen, BMS, Takeda, Celgene, Amgen; consulting or advisory role: Janssen, BMS, Takeda, Celgene, Amgen; research funding: BMS; travel, accomodations, expenses: Janssen, BMS, Takeda, Amgen. HWL: no COI. BHD: no COI. DT: no COI. NG: consulting or advisory role: Pfizer; travel, accomodations, expenses: Celgene, BMS. DH: consulting or advisory role: I. Lamkap Bio AG. Discoveric AG; research funding: Celgene AG. Sanofi. Engmab AG; travel, accomodations, expenses: Celgene. AS: consulting or advisory role: I. Lamkap Bio AG. Discoveric AG; research funding: Celgene AG. Sanofi. Engmab AG. SH: honoraria: Janssen; travel, accomodations, expenses: Celgene. SL: no COI. AJ: no COI. AE: consulting or advisory role: Amgen; travel, accomodations, expenses: Janssen, Amgen. BR: no COI. SF: consulting or advisory role: Sanofi, BMS, Amgen. PB: consulting or advisory role: BMS, AMGEN,Roche, MSD; research funding: BMS; travel, accomodations, expenses: BMS. MG: no COI. HB: no COI. MH: honoraria: MSD. JH: honoraria: AMGEN, Janssen; research funding: Celgene; travel, accomodations, expenses: AMGEN, Janssen. MSR: honoraria: Celgene, BMS, Novartis, Janssen, Takeda; consulting or advisory role: Celgene, BMS, Novartis, Janssen, Takeda; research funding: Celgene, Novartis, AMGEN; travel, accomodations, expenses: Janssen, BMS, Takeda. IWB: research funding: Celgene, BMS, Janssen. MH: honoraria: Novartis, Amgen, Roche, Takeda; consulting or advisory role: Celgene. HJS: honoraria: Celgene, Janssen, Cilag; travel, accomodations, expenses: Celgene, Janssen, Cilag.
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Goldschmidt, H., Mai, E.K., Dürig, J. et al. Response-adapted lenalidomide maintenance in newly diagnosed myeloma: results from the phase III GMMG-MM5 trial. Leukemia 34, 1853–1865 (2020). https://doi.org/10.1038/s41375-020-0724-1
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DOI: https://doi.org/10.1038/s41375-020-0724-1
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