UPDATED OVERALL SURVIVAL ANALYSIS OF THE FIRST STUDY: CONTINUOUS LENALIDOMIDE PLUS LOW-DOSE DEXAMETHASONE VS MELPHALAN, PREDNISONE, AND THALIDOMIDE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA
EHA Library. Facon T. 06/12/15; 103068; S105
Prof. Thierry Facon
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Abstract
Abstract: S105
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 12:30 to 12.06.2015 12:45
Location: Room A2+3
Background
The combination of melphalan, prednisone, and thalidomide (MPT) is considered a standard treatment (Tx) option in many countries for patients (pts) with newly diagnosed multiple myeloma (NDMM) who are ineligible for stem cell transplant (SCT). The FIRST trial is the largest prospective phase 3 trial conducted in pts with NDMM ineligible for SCT. In this study, patients were treated with lenalidomide plus low-dose dexamethasone administered until disease progression or unacceptable toxicity (Rd continuous), Rd for 18 cycles (Rd18), or MPT for 12 cycles. At the planned primary analysis for OS, Rd continuous was associated with improved progression-free survival (PFS) and an overall survival (OS) advantage vs MPT (Benboubker, N Engl J Med, 2014).
Aims
This abstract presents an updated analysis of OS and other efficacy measures that was not initially planned but was requested by regulatory authorities.
Methods
Pts were randomized 1:1:1 to 1 of 3 Tx arms: Rd continuous (28-day cycles), Rd18 (28-day cycles), or MPT for 12 cycles (42-day cycles). Eligible pts (aged ≥ 18 yrs) had symptomatic NDMM and an Eastern Cooperative Oncology Group performance status of 0-2 and were ineligible for SCT. Pts were excluded if they had received prior anti-myeloma Tx, had specified laboratory abnormalities, or had a history of malignancy, other than multiple myeloma, within the past 3 yrs. The primary endpoint was PFS (Rd continuous vs MPT; primary comparison). Secondary endpoints included OS, overall response rate, and safety. Time from randomization to second disease progression (PFS2) or death was included as an additional analysis.
Results
A total of 1623 pts were randomized; 535 pts received Rd continuous, 541 received Rd18, and 547 received MPT. At the time of data cutoff (March 3, 2014), 91 pts remained on Tx with Rd continuous. Across all Tx arms, 697 pts (42.9%) died; 38.9% of pts treated with Rd continuous died compared with 42.1% and 47.7% of pts treated with Rd18 and MPT, respectively. With a median follow-up of 45.5 mos, median OS was 58.9 mos (95% CI, 56.0-not evaluable [NE]) with Rd continuous vs 56.7 mos (95% CI, 50.1-NE) for pts treated with Rd18 and 48.5 mos (95% CI, 44.2-52.0) for pts treated with MPT. For comparison of OS with Rd continuous vs MPT, the hazard ratio (HR) was 0.75 (95% CI, 0.62-0.90). For the updated PFS analysis based on investigators’ assessment, the median was 26.0 mos for pts treated with Rd continuous compared with 21.0 mos with Rd18 and 21.9 mos with MPT. The HR between Rd continuous and MPT was 0.69 (95% CI, 0.59-0.80). The majority of second-line Tx were bortezomib-based (55.7%). PFS2 events occurred in 58% of pts, and the median PFS2 was extended with Rd continuous vs Rd18 and MPT (42.9 vs 40.0 and 35 mos, respectively), with an HR for Rd continuous vs MPT of 0.74 (95% CI, 0.63-0.86). The mean durations of Tx for pts who received Rd continuous, Rd18, and MPT were 22.5, 12.6, and 11.9 mos respectively. Updated safety data will be presented.
Summary
The OS and PFS benefits observed in the original analysis were maintained with Rd continuous. Rd continuous was better tolerated than MPT. The safety profile remained consistent with the interim analysis. Improvements in PFS2 suggest that the benefit of Rd continuous is retained through second-line therapy without inducing resistance. These findings confirm Rd continuous as a new standard of care for pts with NDMM ineligible for SCT.
Session topic: Multiple myeloma: Clinical studies 1
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 12:30 to 12.06.2015 12:45
Location: Room A2+3
Background
The combination of melphalan, prednisone, and thalidomide (MPT) is considered a standard treatment (Tx) option in many countries for patients (pts) with newly diagnosed multiple myeloma (NDMM) who are ineligible for stem cell transplant (SCT). The FIRST trial is the largest prospective phase 3 trial conducted in pts with NDMM ineligible for SCT. In this study, patients were treated with lenalidomide plus low-dose dexamethasone administered until disease progression or unacceptable toxicity (Rd continuous), Rd for 18 cycles (Rd18), or MPT for 12 cycles. At the planned primary analysis for OS, Rd continuous was associated with improved progression-free survival (PFS) and an overall survival (OS) advantage vs MPT (Benboubker, N Engl J Med, 2014).
Aims
This abstract presents an updated analysis of OS and other efficacy measures that was not initially planned but was requested by regulatory authorities.
Methods
Pts were randomized 1:1:1 to 1 of 3 Tx arms: Rd continuous (28-day cycles), Rd18 (28-day cycles), or MPT for 12 cycles (42-day cycles). Eligible pts (aged ≥ 18 yrs) had symptomatic NDMM and an Eastern Cooperative Oncology Group performance status of 0-2 and were ineligible for SCT. Pts were excluded if they had received prior anti-myeloma Tx, had specified laboratory abnormalities, or had a history of malignancy, other than multiple myeloma, within the past 3 yrs. The primary endpoint was PFS (Rd continuous vs MPT; primary comparison). Secondary endpoints included OS, overall response rate, and safety. Time from randomization to second disease progression (PFS2) or death was included as an additional analysis.
Results
A total of 1623 pts were randomized; 535 pts received Rd continuous, 541 received Rd18, and 547 received MPT. At the time of data cutoff (March 3, 2014), 91 pts remained on Tx with Rd continuous. Across all Tx arms, 697 pts (42.9%) died; 38.9% of pts treated with Rd continuous died compared with 42.1% and 47.7% of pts treated with Rd18 and MPT, respectively. With a median follow-up of 45.5 mos, median OS was 58.9 mos (95% CI, 56.0-not evaluable [NE]) with Rd continuous vs 56.7 mos (95% CI, 50.1-NE) for pts treated with Rd18 and 48.5 mos (95% CI, 44.2-52.0) for pts treated with MPT. For comparison of OS with Rd continuous vs MPT, the hazard ratio (HR) was 0.75 (95% CI, 0.62-0.90). For the updated PFS analysis based on investigators’ assessment, the median was 26.0 mos for pts treated with Rd continuous compared with 21.0 mos with Rd18 and 21.9 mos with MPT. The HR between Rd continuous and MPT was 0.69 (95% CI, 0.59-0.80). The majority of second-line Tx were bortezomib-based (55.7%). PFS2 events occurred in 58% of pts, and the median PFS2 was extended with Rd continuous vs Rd18 and MPT (42.9 vs 40.0 and 35 mos, respectively), with an HR for Rd continuous vs MPT of 0.74 (95% CI, 0.63-0.86). The mean durations of Tx for pts who received Rd continuous, Rd18, and MPT were 22.5, 12.6, and 11.9 mos respectively. Updated safety data will be presented.
Summary
The OS and PFS benefits observed in the original analysis were maintained with Rd continuous. Rd continuous was better tolerated than MPT. The safety profile remained consistent with the interim analysis. Improvements in PFS2 suggest that the benefit of Rd continuous is retained through second-line therapy without inducing resistance. These findings confirm Rd continuous as a new standard of care for pts with NDMM ineligible for SCT.
Session topic: Multiple myeloma: Clinical studies 1
Abstract: S105
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 12:30 to 12.06.2015 12:45
Location: Room A2+3
Background
The combination of melphalan, prednisone, and thalidomide (MPT) is considered a standard treatment (Tx) option in many countries for patients (pts) with newly diagnosed multiple myeloma (NDMM) who are ineligible for stem cell transplant (SCT). The FIRST trial is the largest prospective phase 3 trial conducted in pts with NDMM ineligible for SCT. In this study, patients were treated with lenalidomide plus low-dose dexamethasone administered until disease progression or unacceptable toxicity (Rd continuous), Rd for 18 cycles (Rd18), or MPT for 12 cycles. At the planned primary analysis for OS, Rd continuous was associated with improved progression-free survival (PFS) and an overall survival (OS) advantage vs MPT (Benboubker, N Engl J Med, 2014).
Aims
This abstract presents an updated analysis of OS and other efficacy measures that was not initially planned but was requested by regulatory authorities.
Methods
Pts were randomized 1:1:1 to 1 of 3 Tx arms: Rd continuous (28-day cycles), Rd18 (28-day cycles), or MPT for 12 cycles (42-day cycles). Eligible pts (aged ≥ 18 yrs) had symptomatic NDMM and an Eastern Cooperative Oncology Group performance status of 0-2 and were ineligible for SCT. Pts were excluded if they had received prior anti-myeloma Tx, had specified laboratory abnormalities, or had a history of malignancy, other than multiple myeloma, within the past 3 yrs. The primary endpoint was PFS (Rd continuous vs MPT; primary comparison). Secondary endpoints included OS, overall response rate, and safety. Time from randomization to second disease progression (PFS2) or death was included as an additional analysis.
Results
A total of 1623 pts were randomized; 535 pts received Rd continuous, 541 received Rd18, and 547 received MPT. At the time of data cutoff (March 3, 2014), 91 pts remained on Tx with Rd continuous. Across all Tx arms, 697 pts (42.9%) died; 38.9% of pts treated with Rd continuous died compared with 42.1% and 47.7% of pts treated with Rd18 and MPT, respectively. With a median follow-up of 45.5 mos, median OS was 58.9 mos (95% CI, 56.0-not evaluable [NE]) with Rd continuous vs 56.7 mos (95% CI, 50.1-NE) for pts treated with Rd18 and 48.5 mos (95% CI, 44.2-52.0) for pts treated with MPT. For comparison of OS with Rd continuous vs MPT, the hazard ratio (HR) was 0.75 (95% CI, 0.62-0.90). For the updated PFS analysis based on investigators’ assessment, the median was 26.0 mos for pts treated with Rd continuous compared with 21.0 mos with Rd18 and 21.9 mos with MPT. The HR between Rd continuous and MPT was 0.69 (95% CI, 0.59-0.80). The majority of second-line Tx were bortezomib-based (55.7%). PFS2 events occurred in 58% of pts, and the median PFS2 was extended with Rd continuous vs Rd18 and MPT (42.9 vs 40.0 and 35 mos, respectively), with an HR for Rd continuous vs MPT of 0.74 (95% CI, 0.63-0.86). The mean durations of Tx for pts who received Rd continuous, Rd18, and MPT were 22.5, 12.6, and 11.9 mos respectively. Updated safety data will be presented.
Summary
The OS and PFS benefits observed in the original analysis were maintained with Rd continuous. Rd continuous was better tolerated than MPT. The safety profile remained consistent with the interim analysis. Improvements in PFS2 suggest that the benefit of Rd continuous is retained through second-line therapy without inducing resistance. These findings confirm Rd continuous as a new standard of care for pts with NDMM ineligible for SCT.
Session topic: Multiple myeloma: Clinical studies 1
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 12:30 to 12.06.2015 12:45
Location: Room A2+3
Background
The combination of melphalan, prednisone, and thalidomide (MPT) is considered a standard treatment (Tx) option in many countries for patients (pts) with newly diagnosed multiple myeloma (NDMM) who are ineligible for stem cell transplant (SCT). The FIRST trial is the largest prospective phase 3 trial conducted in pts with NDMM ineligible for SCT. In this study, patients were treated with lenalidomide plus low-dose dexamethasone administered until disease progression or unacceptable toxicity (Rd continuous), Rd for 18 cycles (Rd18), or MPT for 12 cycles. At the planned primary analysis for OS, Rd continuous was associated with improved progression-free survival (PFS) and an overall survival (OS) advantage vs MPT (Benboubker, N Engl J Med, 2014).
Aims
This abstract presents an updated analysis of OS and other efficacy measures that was not initially planned but was requested by regulatory authorities.
Methods
Pts were randomized 1:1:1 to 1 of 3 Tx arms: Rd continuous (28-day cycles), Rd18 (28-day cycles), or MPT for 12 cycles (42-day cycles). Eligible pts (aged ≥ 18 yrs) had symptomatic NDMM and an Eastern Cooperative Oncology Group performance status of 0-2 and were ineligible for SCT. Pts were excluded if they had received prior anti-myeloma Tx, had specified laboratory abnormalities, or had a history of malignancy, other than multiple myeloma, within the past 3 yrs. The primary endpoint was PFS (Rd continuous vs MPT; primary comparison). Secondary endpoints included OS, overall response rate, and safety. Time from randomization to second disease progression (PFS2) or death was included as an additional analysis.
Results
A total of 1623 pts were randomized; 535 pts received Rd continuous, 541 received Rd18, and 547 received MPT. At the time of data cutoff (March 3, 2014), 91 pts remained on Tx with Rd continuous. Across all Tx arms, 697 pts (42.9%) died; 38.9% of pts treated with Rd continuous died compared with 42.1% and 47.7% of pts treated with Rd18 and MPT, respectively. With a median follow-up of 45.5 mos, median OS was 58.9 mos (95% CI, 56.0-not evaluable [NE]) with Rd continuous vs 56.7 mos (95% CI, 50.1-NE) for pts treated with Rd18 and 48.5 mos (95% CI, 44.2-52.0) for pts treated with MPT. For comparison of OS with Rd continuous vs MPT, the hazard ratio (HR) was 0.75 (95% CI, 0.62-0.90). For the updated PFS analysis based on investigators’ assessment, the median was 26.0 mos for pts treated with Rd continuous compared with 21.0 mos with Rd18 and 21.9 mos with MPT. The HR between Rd continuous and MPT was 0.69 (95% CI, 0.59-0.80). The majority of second-line Tx were bortezomib-based (55.7%). PFS2 events occurred in 58% of pts, and the median PFS2 was extended with Rd continuous vs Rd18 and MPT (42.9 vs 40.0 and 35 mos, respectively), with an HR for Rd continuous vs MPT of 0.74 (95% CI, 0.63-0.86). The mean durations of Tx for pts who received Rd continuous, Rd18, and MPT were 22.5, 12.6, and 11.9 mos respectively. Updated safety data will be presented.
Summary
The OS and PFS benefits observed in the original analysis were maintained with Rd continuous. Rd continuous was better tolerated than MPT. The safety profile remained consistent with the interim analysis. Improvements in PFS2 suggest that the benefit of Rd continuous is retained through second-line therapy without inducing resistance. These findings confirm Rd continuous as a new standard of care for pts with NDMM ineligible for SCT.
Session topic: Multiple myeloma: Clinical studies 1
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