Salvage autologous transplant and lenalidomide maintenance vs. lenalidomide/dexamethasone for relapsed multiple myeloma: the randomized GMMG phase III trial ReLApsE

Goldschmidt, Hartmut; Baertsch, Marc‐Andrea; Schlenzka, Jana; Becker, Natália; Habermehl, Christina; Hielscher, Thomas; Raab, Marc-Steffen; Hillengaß, Jens; Sauer, Sandra; Müller-Tidow, Carsten; Luntz, Steffen; Jauch, Anna; Hose, Dirk; Seckinger, Anja; Brossart, Peter; Göerner, Martin; Klein, Stefan; Schmidt‐Hieber, Martin; Reimer, Peter; Graeven, Ullrich; Fenk, Roland; Haenel, Mathias; Martin, Hans; Lindemann, Hans Walter; Scheid, Christoph; Nogai, Axel; Salwender, Hans; Noppeney, Richard; Besemer, Britta; Weisel, Katja

doi:10.1038/s41375-020-0948-0

Cited by 41 publications

(26 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multivariate landmark analyses from the time of ASCT showed superior PFS and OS (P ¼ 0.0087 and P ¼ 0.0057 respectively) in patients who received ASCT. 50 The American and European Associations for Bone and Marrow Transplantation have reported that HDT and ASCT should be considered appropriate treatment of any patient relapsing after primary therapy that includes an ASCT with initial remission duration of >18 months. 51 However, this recommendation was made before the broad use of lenalidomide as maintenance therapy post-ASCT.…”

Section: Patients Who Have Received One Prior Line Of Therapymentioning

confidence: 99%

Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†

Moreau²,

et al. 2021

View full text Add to dashboard Cite

show abstract

Section: Patients Who Have Received One Prior Line Of Therapymentioning

confidence: 99%

Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†

Moreau²,

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However, evidence for its benefit in the era of novel agents is limited [ 12 ]. The only randomized controlled phase III trial (GMMG ReLApsE) that compared a novel agent regimen including salvage HDCT/ASCT versus continuous novel agent treatment (LEN/dexamethasone[DEX]) failed to show a PFS (21 vs. 19 months) or OS (not reached vs. 63 months) benefit in the primary analysis but was hampered by a ~ 30% discontinuation rate before the transplant step [ 13 ]. Post-hoc landmark analyses of this trial suggested that some benefit was retained in patients that actually received salvage HDCT/ASCT.…”

Section: Introductionmentioning

confidence: 99%

Carfilzomib, Lenalidomide, and Dexamethasone Followed by Salvage Autologous Stem Cell Transplant with or without Maintenance for Relapsed or Refractory Multiple Myeloma

Baertsch

Fougereau

Hielscher

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

Salvage high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) is a treatment option for relapsed and/or refractory multiple myeloma (RRMM). No data are available on salvage HDCT/ASCT following re-induction treatment with state-of-the-art triplet regimens. We retrospectively report on 44 patients receiving salvage HDCT/ASCT following re-induction with carfilzomib/lenalidomide/dexamethasone (KRd). All patients received frontline HDCT/ASCT with median time to progression (TTP1) of 2.9 (1.2–13.5) years, enabling paired comparison of frontline and salvage HDCT/ASCT. After re-induction and before salvage transplant, 25/44 patients (57%) attained ≥ very good partial response (VGPR), which increased to 34/44 (77%) at best response after salvage HDCT/ASCT. Median progression-free survival (PFS) was 23.3 months from salvage HDCT/ASCT. Patients with ≥ VGPR at the time of salvage HDCT/ASCT and those receiving maintenance treatment post salvage HDCT/ASCT had significantly superior PFS (hazard ratio (HR) 0.19, p = 0.001 and HR 0.20, p = 0.009). In patients achieving at least an equal depth of response before salvage HDCT/ASCT as before frontline HDCT/ASCT, PFS after salvage HDCT/ASCT was comparable to the frontline situation (p = 0.3). This is the first report of state-of-the-art triplet re-induction and salvage HDCT/ASCT for RRMM after frontline transplantation. Deep remissions achieved with KRd translate into prolonged PFS following salvage HDCT/ASCT and are enhanced by maintenance treatment.

show abstract

“…This outcome also compares favorably with the PFS described in phase 3 trials of pharmacological interventions that included lenalidomide‐refractory patients, such as Kd in the ENDEAVOR study, PVd as per the OPTIMMISM study, and DVd as per the CASTOR trial 12‐14 . Of note, the recently reported ReLApsE trial comparing second ASCT at time of relapse versus more modern chemotherapy did not include patients who progressed on lenalidomide and hence does not address this question 18 . It will be important to determine whether the interjection of ASCT before the use of an anti‐CD38 monoclonal antibody regimen compromises the benefit of this important therapeutic modality when utilized for a subsequent relapse, or whether ASCT adds another beneficial line of therapy in a disease in which cure has been elusive.…”

Section: Discussionmentioning

confidence: 92%

Retrospective study of treatment patterns and outcomes post‐lenalidomide for multiple myeloma in Canada

Reece

Masih‐Khan

Atenafu³

et al. 2021

European J of Haematology

View full text Add to dashboard Cite

Lenalidomide is an important component of initial therapy in newly diagnosed multiple myeloma, either as maintenance therapy post‐autologous stem cell transplantation (ASCT) or as first‐line therapy with dexamethasone for patients’ ineligible for ASCT (non‐ASCT). This retrospective study investigated treatment patterns and outcomes for ASCT‐eligible and ‐ineligible patients who relapsed after lenalidomide as part of first‐line therapy, based on data from the Canadian Myeloma Research Group Database for patients treated between January 2007 and April 2019. Among 256 patients who progressed on lenalidomide maintenance therapy, 28.5% received further immunomodulatory derivative‐based (IMiD‐based) therapy (lenalidomide/pomalidomide) without a proteasome inhibitor (PI) (bortezomib/carfilzomib/ixazomib), 26.2% received PI‐based therapy without an IMiD, 19.5% received both an IMiD plus PI, 13.5% received daratumumab‐based regimens, and 12.1% underwent salvage ASCT. Median progression‐free survival (PFS) was longest for daratumumab‐based therapy (22.7 months) and salvage ASCT (23.4 months) and ranged from 6.6 to 7.3 months for the other treatments (P < .0001). Median overall survival (OS) was also longest for daratumumab and salvage ASCT. A total of 87 non‐ASCT patients received subsequent therapy, with 66.7% receiving bortezomib‐based therapy and 13.8% receiving other PI‐based therapy. Median PFS was 15.4 and 24.8 months for bortezomib‐based and other PI‐based therapy, respectively (P = .404). During most of the study period, daratumumab was not funded; in this setting, switching to a different therapeutic class following relapse on lenalidomide produced the longest remissions for non‐ASCT patients. Further prospective studies are warranted to determine optimum treatment following relapse on lenalidomide, especially in the light of increased access to daratumumab.

show abstract

Salvage autologous transplant and lenalidomide maintenance vs. lenalidomide/dexamethasone for relapsed multiple myeloma: the randomized GMMG phase III trial ReLApsE

Cited by 41 publications

References 27 publications

Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†

Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†

Carfilzomib, Lenalidomide, and Dexamethasone Followed by Salvage Autologous Stem Cell Transplant with or without Maintenance for Relapsed or Refractory Multiple Myeloma

Retrospective study of treatment patterns and outcomes post‐lenalidomide for multiple myeloma in Canada

Contact Info

Product

Resources

About