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Clinical Trial
. 2017 Sep;178(6):896-905.
doi: 10.1111/bjh.14787. Epub 2017 Jul 5.

Elotuzumab plus lenalidomide/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT-2 follow-up and post-hoc analyses on progression-free survival and tumour growth

Meletios A Dimopoulos  1 , Sagar Lonial  2 , Darrell White  3 , Philippe Moreau  4 , Antonio Palumbo  5 , Jesus San-Miguel  6 , Ofer Shpilberg  7 , Kenneth Anderson  8 , Sebastian Grosicki  9 , Ivan Spicka  10 , Adam Walter-Croneck  11 , Hila Magen  12 , Maria-Victoria Mateos  13 , Andrew Belch  14 , Donna Reece  15 , Meral Beksac  16 , Eric Bleickardt  17 , Valerie Poulart  18 , Jennifer Sheng  19 , Oumar Sy  20 , Jessica Katz  21 , Anil Singhal  22 , Paul Richardson  23
Affiliations
Clinical Trial

Elotuzumab plus lenalidomide/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT-2 follow-up and post-hoc analyses on progression-free survival and tumour growth

Meletios A Dimopoulos et al. Br J Haematol. 2017 Sep.

Abstract

The randomized phase III ELOQUENT-2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab + lenalidomide/dexamethasone (ELd) versus lenalidomide/dexamethasone (Ld) in relapsed/refractory multiple myeloma. ELd reduced the risk of disease progression/death by 30% versus Ld (hazard ratio [HR] 0·70). Median time from diagnosis was 3·5 years. We present extended 3-year follow-up data. Endpoints included progression-free survival (PFS), overall response rate (ORR) and interim overall survival (OS). Exploratory post-hoc analyses included impact of time from diagnosis and prior lines of therapy on PFS, and serum M-protein dynamic modelling. ORR was 79% (ELd) and 66% (Ld) (P = 0·0002). ELd reduced the risk of disease progression/death by 27% versus Ld (HR 0·73; P = 0·0014). Interim OS demonstrated a trend in favour of ELd (P = 0·0257); 1-, 2- and 3-year rates with ELd versus Ld were: 91% versus 83%, 73% versus 69% and 60% versus 53%. In patients with ≥ median time from diagnosis and one prior therapy, ELd resulted in a 53% reduction in the risk of progression/death versus Ld (HR 0·47). Serum M-protein dynamic modelling showed slower tumour regrowth with ELd. Adverse events were comparable between arms. ELd provided a durable and clinically relevant improvement in efficacy, with minimal incremental toxicity.

Keywords: elotuzumab; monoclonal antibody; multiple myeloma; overall survival; progression-free survival.

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Figures

Figure 1
Figure 1
Serum M‐protein dynamic modelling. (A) Tumour growth dynamic modelling concept, (B) simulated longitudinal M protein in patients with ≥ median time from diagnosis, (C) simulated longitudinal M protein in patients with < median time from diagnosis. A, tumour size at t; A0, baseline tumour size; CV%, coefficient of variation (CV% = [std/mean] × 100); ELd, elotuzumab + lenalidomide/dexamethasone; kg, rate of tumour regrowth; ks, rate of tumour shrinkage; Ld, lenalidomide/dexamethasone; t, time.
Figure 2
Figure 2
Kaplan–Meier curves of PFS (primary definition). CI, confidence interval; ELd, elotuzumab + lenalidomide/dexamethasone; HR, hazard ratio; Ld, lenalidomide/dexamethasone; PFS, progression‐free survival.
Figure 3
Figure 3
(A) PFS by predefined subgroups and (B) Kaplan–Meier curves of PFS (primary definition), stratified by median time from diagnosis and number of prior lines of therapy. aPatients were considered del(17p) positive if any cell was positive. *Interaction P‐value corresponds to del(17p) (yes) versus del(17p) (no); †Interaction P‐value corresponds to t(4:14) (yes) versus t(4:14) (no). CI, confidence interval; ELd, elotuzumab + lenalidomide/dexamethasone; HR, hazard ratio; IMiD, immunomodulatory drug; ISS, International Staging System; Ld, lenalidomide/dexamethasone; PFS, progression‐free survival.
Figure 4
Figure 4
Kaplan–Meier curves of PFS (intent‐to‐treat definition). CI, confidence interval; ELd, elotuzumab + lenalidomide/dexamethasone; HR, hazard ratio; Ld, lenalidomide/dexamethasone; PFS, progression‐free survival.
Figure 5
Figure 5
Kaplan–Meier curves of OS. CI, confidence interval; ELd, elotuzumab + lenalidomide/dexamethasone; HR, hazard ratio; Ld, lenalidomide/dexamethasone; NE, not evaluable; OS, overall survival.
Figure 6
Figure 6
OS by predefined subgroups. aPatients were considered del(17p) positive if any cell was positive; *Interaction P‐value corresponds to del(17p) (yes) versus del(17p) (no); †Interaction P‐value corresponds to t(4:14) (yes) versus t(4:14) (no). CI, confidence interval; ELd, elotuzumab + lenalidomide/dexamethasone; HR, hazard ratio; IMiD, immunomodulatory drug; ISS, International Staging System; Ld, lenalidomide/dexamethasone; OS, overall survival.
Figure 7
Figure 7
Kaplan–Meier curves of TTNT. CI, confidence interval; ELd, elotuzumab + lenalidomide/dexamethasone; HR, hazard ratio; Ld, lenalidomide/dexamethasone; TTNT, time to next treatment.
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