LENALIDOMIDE MAINTENANCE VS PLACEBO AFTER STEM CELL TRANSPLANT FOR PATIENTS WITH MULTIPLE MYELOMA: OVERALL SURVIVAL AND PROGRESSION-FREE SURVIVAL AFTER ADJUSTING FOR TREATMENT CROSSOVER IN CALGB
Author(s): ,
Philip L. McCarthy
Affiliations:
Blood and Marrow Transplant Program, Roswell Park Cancer Institute,Buffalo, NY,United States
,
Sarah A. Holstein
Affiliations:
University of Nebraska Medical Center,Omaha, NE,United States
,
Sin-Ho Jung
Affiliations:
Alliance Statistics and Data Center, Duke University,Durham, NC,United States
,
Miranda Cooper
Affiliations:
BresMed,Sheffield,United Kingdom
,
Craig J. Gibson
Affiliations:
Celgene Corporation,Summit, NJ,United States
,
Edward A. Stadtmauer
Affiliations:
Abramson Cancer Center, University of Pennsylvania,Philadelphia, PA,United States
,
Benjamin Winograd
Affiliations:
Celgene Corporation,Summit, NJ,United States
Paul Richardson
Affiliations:
Dana-Farber/Partners CancerCare,Boston, MA,United States
EHA Library. L. McCarthy P. 06/23/17; 181619; P332
Philip L. McCarthy
Philip L. McCarthy
Contributions
Abstract

Abstract: P332

Type: Poster Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 17:15 - 18:45

Location: Poster area (Hall 7)

Background
At a prespecified interim analysis (December 2009), the phase 3 CALGB/ECOG 100104 (Alliance) study results surpassed the prespecified superiority boundary (significantly improved progression-free survival [PFS] for lenalidomide [LEN] maintenance vs placebo [PBO] after SCT) and the majority of PBO arm patients without progressive disease (PD) crossed over to LEN maintenance. An updated analysis (cutoff March 2015), showed significantly longer overall survival [OS] with LEN maintenance (HR, 0.56; 95% CI, 0.42-0.76). However, the crossover from PBO to LEN makes it difficult to assess the true treatment effect of LEN.

Aims
To examine the effect of LEN vs PBO on OS and PFS from randomization, adjusting for effects of crossover.

Methods
The rank-preserving structural failure time model (RPSFTM; Robins, Commun Stat Theory Methods, 1991) was used for crossover adjustment; the iterative parameter estimation (IPE; Branson, Stat Med, 2002) algorithm was used as validation. Survival was partitioned assuming a residual LEN effect after discontinuation. A landmark analysis was also performed at the Dec 2009 interim for patients who remained on treatment. Patients in the trial provided informed consent.

Results
Patients were randomized to LEN maintenance (n = 231) and PBO (n = 229) (intent-to-treat [ITT] population); 76 patients without PD crossed over from PBO to LEN. The median time from randomization to crossover was 11.5 months. The relative treatment effect for OS and PFS increased for LEN vs PBO when adjusting for crossover using RPSFTM and IPE (Table). The landmark analysis at the Dec 2009 interim (PBO crossover, n = 76; No crossover, n = 34) showed the treatment effect is not dissimilar to the ITT analysis (HR 0.53; 95% CI, 0.25-1.13). Sensitivity analyses showed consistent results. Updated data will be presented at the meeting.

Conclusion
Adjusting for the potential diluting effects of crossover reduced median OS and PFS with PBO, and improved the treatment effect in the ITT analyses for OS and PFS for LEN vs PBO maintenance after SCT. The statistical significance of the ITT analyses was maintained throughout.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Maintenance, Immunomodulatory thalidomide analog, Post-transplant, Multiple Myeloma

Abstract: P332

Type: Poster Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 17:15 - 18:45

Location: Poster area (Hall 7)

Background
At a prespecified interim analysis (December 2009), the phase 3 CALGB/ECOG 100104 (Alliance) study results surpassed the prespecified superiority boundary (significantly improved progression-free survival [PFS] for lenalidomide [LEN] maintenance vs placebo [PBO] after SCT) and the majority of PBO arm patients without progressive disease (PD) crossed over to LEN maintenance. An updated analysis (cutoff March 2015), showed significantly longer overall survival [OS] with LEN maintenance (HR, 0.56; 95% CI, 0.42-0.76). However, the crossover from PBO to LEN makes it difficult to assess the true treatment effect of LEN.

Aims
To examine the effect of LEN vs PBO on OS and PFS from randomization, adjusting for effects of crossover.

Methods
The rank-preserving structural failure time model (RPSFTM; Robins, Commun Stat Theory Methods, 1991) was used for crossover adjustment; the iterative parameter estimation (IPE; Branson, Stat Med, 2002) algorithm was used as validation. Survival was partitioned assuming a residual LEN effect after discontinuation. A landmark analysis was also performed at the Dec 2009 interim for patients who remained on treatment. Patients in the trial provided informed consent.

Results
Patients were randomized to LEN maintenance (n = 231) and PBO (n = 229) (intent-to-treat [ITT] population); 76 patients without PD crossed over from PBO to LEN. The median time from randomization to crossover was 11.5 months. The relative treatment effect for OS and PFS increased for LEN vs PBO when adjusting for crossover using RPSFTM and IPE (Table). The landmark analysis at the Dec 2009 interim (PBO crossover, n = 76; No crossover, n = 34) showed the treatment effect is not dissimilar to the ITT analysis (HR 0.53; 95% CI, 0.25-1.13). Sensitivity analyses showed consistent results. Updated data will be presented at the meeting.

Conclusion
Adjusting for the potential diluting effects of crossover reduced median OS and PFS with PBO, and improved the treatment effect in the ITT analyses for OS and PFS for LEN vs PBO maintenance after SCT. The statistical significance of the ITT analyses was maintained throughout.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Maintenance, Immunomodulatory thalidomide analog, Post-transplant, Multiple Myeloma

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