Advanced

Lenalidomide versus lenalidomide + dexamethasone prolonged treatment after second-line lenalidomide + dexamethasone induction in multiple myeloma

Lund, Johan; Gruber, Astrid; Lauri, Birgitta; Duru, Adil Doganay; Blimark, Cecilie; Swedin, Agneta; Hansson, Markus LU ; Forsberg, Karin; Ahlberg, Lucia and Carlsson, Conny, et al. (2018) In Cancer Medicine
Abstract

Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or refractory multiple myeloma (RRMM). It is possible that single-agent Len may be effective as prolonged treatment regimen in RRMM once patients demonstrate an initial response to Len+Dex induction. Patients with RRMM who responded to first-line Len+Dex in an observational study (NCT01430546) received up to 24 cycles of either Len (25 mg/day) or Len+Dex (25 mg/day and 40 mg/week) as prolonged treatment in a subsequent phase 2 clinical trial (NCT01450215). In the observational study (N = 133), median time to response was 1.7 (range 0.6-9.6) months. A complete response to all treatments received in both studies was observed in 11% of patients; very good... (More)

Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or refractory multiple myeloma (RRMM). It is possible that single-agent Len may be effective as prolonged treatment regimen in RRMM once patients demonstrate an initial response to Len+Dex induction. Patients with RRMM who responded to first-line Len+Dex in an observational study (NCT01430546) received up to 24 cycles of either Len (25 mg/day) or Len+Dex (25 mg/day and 40 mg/week) as prolonged treatment in a subsequent phase 2 clinical trial (NCT01450215). In the observational study (N = 133), median time to response was 1.7 (range 0.6-9.6) months. A complete response to all treatments received in both studies was observed in 11% of patients; very good partial response and partial response rates were 31% and 38%, respectively. Corresponding response rates in the subgroup of patients who did not enter the phase 2 trial (n = 71) were 3%, 18%, and 39%, respectively. Rates of disease progression at 2 years in the phase 2 trial were 47% versus 31% for Len versus Len+Dex (P = 0.14). After 36 months median follow-up in surviving patients, median time to progression was not reached with Len+Dex and was 24.9 months (95% confidence interval 12.5-not calculable, P < 0.001) with Len. Three-year OS among the total observational study population was 61% (95% CI, 52-69%). The corresponding rate among patients who entered the phase 2 clinical trial was 73% (95% CI, 60-83%) and was significantly lower among those patients who achieved ≥PR but did not proceed into the phase 2 trial (55%; P = 0.01). In the phase 2 trial, OS was 73% in both treatment arms (P = 0.70). Neutropenia and thrombocytopenia were more common with prolonged (phase 2 trial) versus short-term (observational study) Len administration but remained manageable. Prolonged treatment with Len with or without Dex provides sustained, clinically relevant responses and demonstrates an acceptable safety profile.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Clinical Trial, Lenalidomide, Multiple Myeloma
in
Cancer Medicine
publisher
Wiley-Blackwell
external identifiers
  • scopus:85045848380
ISSN
2045-7634
DOI
10.1002/cam4.1422
language
English
LU publication?
no
id
f1c7b62a-ae74-47f4-9c60-bb2792995336
date added to LUP
2018-05-04 13:42:48
date last changed
2019-01-06 13:53:29
@article{f1c7b62a-ae74-47f4-9c60-bb2792995336,
  abstract     = {<p>Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or refractory multiple myeloma (RRMM). It is possible that single-agent Len may be effective as prolonged treatment regimen in RRMM once patients demonstrate an initial response to Len+Dex induction. Patients with RRMM who responded to first-line Len+Dex in an observational study (NCT01430546) received up to 24 cycles of either Len (25 mg/day) or Len+Dex (25 mg/day and 40 mg/week) as prolonged treatment in a subsequent phase 2 clinical trial (NCT01450215). In the observational study (N = 133), median time to response was 1.7 (range 0.6-9.6) months. A complete response to all treatments received in both studies was observed in 11% of patients; very good partial response and partial response rates were 31% and 38%, respectively. Corresponding response rates in the subgroup of patients who did not enter the phase 2 trial (n = 71) were 3%, 18%, and 39%, respectively. Rates of disease progression at 2 years in the phase 2 trial were 47% versus 31% for Len versus Len+Dex (P = 0.14). After 36 months median follow-up in surviving patients, median time to progression was not reached with Len+Dex and was 24.9 months (95% confidence interval 12.5-not calculable, P &lt; 0.001) with Len. Three-year OS among the total observational study population was 61% (95% CI, 52-69%). The corresponding rate among patients who entered the phase 2 clinical trial was 73% (95% CI, 60-83%) and was significantly lower among those patients who achieved ≥PR but did not proceed into the phase 2 trial (55%; P = 0.01). In the phase 2 trial, OS was 73% in both treatment arms (P = 0.70). Neutropenia and thrombocytopenia were more common with prolonged (phase 2 trial) versus short-term (observational study) Len administration but remained manageable. Prolonged treatment with Len with or without Dex provides sustained, clinically relevant responses and demonstrates an acceptable safety profile.</p>},
  author       = {Lund, Johan and Gruber, Astrid and Lauri, Birgitta and Duru, Adil Doganay and Blimark, Cecilie and Swedin, Agneta and Hansson, Markus and Forsberg, Karin and Ahlberg, Lucia and Carlsson, Conny and Waage, Anders and Gimsing, Peter and Vangsted, Annette Juul and Frølund, Ulf and Holmberg, Erik and Gahrton, Gösta and Alici, Evren and Hardling, Mats and Mellqvist, Ulf Henrik and Nahi, Hareth},
  issn         = {2045-7634},
  keyword      = {Clinical Trial,Lenalidomide,Multiple Myeloma},
  language     = {eng},
  month        = {01},
  publisher    = {Wiley-Blackwell},
  series       = {Cancer Medicine},
  title        = {Lenalidomide versus lenalidomide + dexamethasone prolonged treatment after second-line lenalidomide + dexamethasone induction in multiple myeloma},
  url          = {http://dx.doi.org/10.1002/cam4.1422},
  year         = {2018},
}