IMPACT OF STABLE DISEASE AS A RESPONSE TO POMALIDOMIDE PLUS LOW-DOSE DEXAMETHASONE ON SURVIVAL OUTCOMES IN PATIENTS WITH REFRACTORY OR RELAPSED AND REFRACTORY MULTIPLE MYELOMA IN THE MM-003 TRIAL
Author(s): ,
Philippe Moreau
Affiliations:
University Hospital Hôtel-Dieu,Nantes,France
,
Katja Weisel
Affiliations:
University Hospital of Tuebingen,Tuebingen,Germany
,
Kevin Song
Affiliations:
Vancouver General Hospital,Vancouver,Canada
,
Craig Gibson
Affiliations:
Celgene Corporation,Summit,United States
,
Owain Saunders
Affiliations:
BresMed Health Solutions,Sheffield,United Kingdom
,
Lars Sternas
Affiliations:
Celgene Corporation,Summit,United States
,
Kevin Hong
Affiliations:
Celgene Corporation,Summit,United States
,
Mohamed Zaki
Affiliations:
Celgene Corporation,Summit,United States
Meletios A Dimopoulos
Affiliations:
National and Kapodistrian University of Athens,Athens,Greece
EHA Library. Moreau P. 06/14/15; 103056; S788
Prof. Philippe Moreau
Prof. Philippe Moreau
Contributions
Abstract
Abstract: S788

Type: Oral Presentation

Presentation during EHA20: From 14.06.2015 08:45 to 14.06.2015 09:00

Location: Room A2+3

Background
Patients (pts) with refractory or relapsed and refractory multiple myeloma (RRMM) have poor overall survival (OS) outcomes after failure of bortezomib and lenalidomide treatment (Tx) regimens. Pomalidomide plus low-dose dexamethasone (POM + LoDEX) has been demonstrated to significantly extend OS in this pt population compared with high-dose DEX (HiDEX; hazard ratio [HR] = 0.74 [95% CI, 0.56-0.97]; P = 0.0285; San Miguel et al, Lancet Oncol, 2013) in the phase 3 MM-003 trial (clinicaltrials.gov identifier NCT01311687). Secondary analysis of MM-003 showed that the survival benefit of Tx with POM + LoDEX extended to pts who achieved minor response or better (San Miguel et al, ASH, 2013).

Aims
This post hoc analysis of MM-003 investigated OS based on response status with a focus on pts who achieved stable disease (SD) but not a response by certain landmark points in time.

Methods
Kaplan-Meier methods and unadjusted Cox regression models were used for landmark analyses at the start of cycles (C) 3, 5, and 7. Response status was captured over time by time-dependent survival analyses. For both approaches, survival of pts with SD was compared with that of pts with progressive disease (PD) or overall response (OR; ≥ partial response) at the same point in their treatment.

Results
302 pts randomized to POM + LoDEX were included in the analysis. Response rates at C3 were 38.4% SD, 14.6% PD, and 19.2% OR, with no response data for 27.8% of pts (mostly due to early discontinuation). The median OS from randomization by response status at C3 was 15.3 mos for SD (n = 116), 6.3 mos for PD (n = 44; hazard ratio [HR] = 3.83; P < 0.0001 vs SD), and 17.5 mos for OR (n = 58; HR = 0.75; P = 0.320 vs SD). Median OS at C5 was 16.6 mos for SD (n = 57), 11.0 mos for PD (n = 31; HR = 2.81; P = 0.004 vs SD), and 18.0 mos for OR (n = 56; HR = 0.74; P = 0.462 vs SD). Median OS at C7 was not reached for SD (n = 40), 16.4 mos for PD (n = 18; HR = 2.66; P = 0.080 vs SD), and 18.0 mos for OR (n = 47; HR = 0.90; P = 0.843 vs SD). The time-dependent survival model showed a lower risk of death for pts with SD or OR vs PD (HR = 0.27 [95% CI, 0.17-0.44] and HR = 0.06 [95% CI, 0.02-0.16], respectively). The HiDEX Tx arm exhibited a lower response rate and shorter OS, which in combination with a smaller number of pts overall resulted in response groups too small for meaningful analysis.

Summary
POM + LoDEX–treated pts with SD at C3, C5, and C7 had OS comparable to pts who achieved OR. The OS of pts with either SD or OR at these time points was significantly longer than for those with PD.

Session topic: Multiple myeloma: Clinical studies 3
Abstract: S788

Type: Oral Presentation

Presentation during EHA20: From 14.06.2015 08:45 to 14.06.2015 09:00

Location: Room A2+3

Background
Patients (pts) with refractory or relapsed and refractory multiple myeloma (RRMM) have poor overall survival (OS) outcomes after failure of bortezomib and lenalidomide treatment (Tx) regimens. Pomalidomide plus low-dose dexamethasone (POM + LoDEX) has been demonstrated to significantly extend OS in this pt population compared with high-dose DEX (HiDEX; hazard ratio [HR] = 0.74 [95% CI, 0.56-0.97]; P = 0.0285; San Miguel et al, Lancet Oncol, 2013) in the phase 3 MM-003 trial (clinicaltrials.gov identifier NCT01311687). Secondary analysis of MM-003 showed that the survival benefit of Tx with POM + LoDEX extended to pts who achieved minor response or better (San Miguel et al, ASH, 2013).

Aims
This post hoc analysis of MM-003 investigated OS based on response status with a focus on pts who achieved stable disease (SD) but not a response by certain landmark points in time.

Methods
Kaplan-Meier methods and unadjusted Cox regression models were used for landmark analyses at the start of cycles (C) 3, 5, and 7. Response status was captured over time by time-dependent survival analyses. For both approaches, survival of pts with SD was compared with that of pts with progressive disease (PD) or overall response (OR; ≥ partial response) at the same point in their treatment.

Results
302 pts randomized to POM + LoDEX were included in the analysis. Response rates at C3 were 38.4% SD, 14.6% PD, and 19.2% OR, with no response data for 27.8% of pts (mostly due to early discontinuation). The median OS from randomization by response status at C3 was 15.3 mos for SD (n = 116), 6.3 mos for PD (n = 44; hazard ratio [HR] = 3.83; P < 0.0001 vs SD), and 17.5 mos for OR (n = 58; HR = 0.75; P = 0.320 vs SD). Median OS at C5 was 16.6 mos for SD (n = 57), 11.0 mos for PD (n = 31; HR = 2.81; P = 0.004 vs SD), and 18.0 mos for OR (n = 56; HR = 0.74; P = 0.462 vs SD). Median OS at C7 was not reached for SD (n = 40), 16.4 mos for PD (n = 18; HR = 2.66; P = 0.080 vs SD), and 18.0 mos for OR (n = 47; HR = 0.90; P = 0.843 vs SD). The time-dependent survival model showed a lower risk of death for pts with SD or OR vs PD (HR = 0.27 [95% CI, 0.17-0.44] and HR = 0.06 [95% CI, 0.02-0.16], respectively). The HiDEX Tx arm exhibited a lower response rate and shorter OS, which in combination with a smaller number of pts overall resulted in response groups too small for meaningful analysis.

Summary
POM + LoDEX–treated pts with SD at C3, C5, and C7 had OS comparable to pts who achieved OR. The OS of pts with either SD or OR at these time points was significantly longer than for those with PD.

Session topic: Multiple myeloma: Clinical studies 3

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