UPFRONT OR RESCUE TRANSPLANT IN YOUNG PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: A POOLED ANALYSIS OF 529 PATIENTS
(Abstract release date: 05/19/16)
EHA Library. Gay F. 06/10/16; 135137; S104
Dr. Francesca Gay
Contributions
Contributions
Abstract
Abstract: S104
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 12:30 - 12:45
Location: Hall A1
Background
In patients with newly diagnosed myeloma, upfront Melphalan 200 mg/m2 followed by ASCT (MEL200-ASCT) prolongs progression-free survival-1 (PFS1) in comparison with chemotherapy plus lenalidomide (CC+R) but ASCT as salvage therapy at first relapse may still effectively rescue patients who did not receive upfront ASCT.
Aims
The primary aim was to evaluate the long-term benefit of upfront ASCT vs CC+R, including the impact of MEL200-ASCT vs CC+R in specific subgroups of patients with different prognostic features. The secondary aim was to evaluate the efficacy of salvage ASCT in patients receiving upfront CC+R.
Methods
We performed an individual patient data meta-analysis of patients enrolled in 2 phase III trials (RV-MM-209 and EMN-441) that randomized patients to MEL200-ASCT vs CC+R. Primary endpoints were PFS1, PFS2, overall survival (OS). Subgroup analyses according to baseline features, protocol and post MEL200-ASCT/CC+R maintenance were performed. We calculated the odds ratio (ORs) with 95% confidence intervals (CIs), as measure of association between the upfront and rescue therapy (MEL200-ASCT vs CC+R followed by rescue ASCT) with the 4-year risk of second progression/death (PFS2) and death (OS).
Results
In the pooled analysis, 268 patients were randomized to MEL200-ASCT and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 in comparison with CC+R (median 42 vs 24 months, HR 0.53; P<0.001), with a significant advantage in all the subgroups analyzed. In patients with R-ISS Stage I the 4-year PFS1 was 53% with MEL200-ASCT vs 36% with CC+R; in patients with R-ISS Stage II/III the 4-year PFS1 was 41% with MEL200-ASCT vs 23% with CC+R. 134 MEL200-ASCT patients and 176 CC+R patients experienced first progression. 125 patients in the MEL200-ASCT group and 174 in the CC+R group received second-line therapy. MEL200-ASCT significantly prolonged PFS2 in comparison with CC+R (4-year PFS2: 71% vs 54%, HR 0.53, p<0.001). The long-term advantage of MEL200-ASCT was evident in good and bad prognosis patients: in patients with R-ISS Stage I, the 4-year PFS2 was 83% with MEL200-ASCT vs 71% with CC+R; in patients with R-ISS Stage II/III the 4-year PFS2 was 67% with MEL200-ASCT and 48% with CC+R. The PFS1 and PFS2 advantage translated into a significant OS benefit for patients randomized to MEL200-ASCT in comparison with CC+R (4-year OS: 84% vs 70%, HR 0.51, P<0.001). Subgroup analyses of OS were limited by a lower number of events but the advantage with MEL200-ASCT was still evident in most of the subgroups analyzed. At data cut off, in the MEL200-ASCT group, 9% of patients received again ASCT, 68% bortezomib, 16% immunomodulatory agents (IMIDs), 7% other therapies. In the CC+R group, ASCT was recommended but not mandatory at relapse, and the choice of therapy was based on patient’s will and physician discretion according to patient eligibility to ASCT: 53% of patients received ASCT, 38% bortezomib regimens, 6% IMIDs, and 3% other therapies. Upfront ASCT regardless of salvage therapy significantly reduced the risk of second progression/death (OR 0.31; P<0.001) and death (OR 0.41; P=0.003) at 4 years in comparison with CC+R followed by salvage ASCT.
Conclusion
MEL200-ASCT significantly improved PFS1, PFS2 and OS in comparison with CC+R in good and bad prognosis patients. Upfront ASCT significantly reduced the risk of death in comparison with CC+R and salvage ASCT. These data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.
Session topic: New agents for Myeloma treatment
Keyword(s): Chemotherapy, Imids, Multiple myeloma, Transplant
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 12:30 - 12:45
Location: Hall A1
Background
In patients with newly diagnosed myeloma, upfront Melphalan 200 mg/m2 followed by ASCT (MEL200-ASCT) prolongs progression-free survival-1 (PFS1) in comparison with chemotherapy plus lenalidomide (CC+R) but ASCT as salvage therapy at first relapse may still effectively rescue patients who did not receive upfront ASCT.
Aims
The primary aim was to evaluate the long-term benefit of upfront ASCT vs CC+R, including the impact of MEL200-ASCT vs CC+R in specific subgroups of patients with different prognostic features. The secondary aim was to evaluate the efficacy of salvage ASCT in patients receiving upfront CC+R.
Methods
We performed an individual patient data meta-analysis of patients enrolled in 2 phase III trials (RV-MM-209 and EMN-441) that randomized patients to MEL200-ASCT vs CC+R. Primary endpoints were PFS1, PFS2, overall survival (OS). Subgroup analyses according to baseline features, protocol and post MEL200-ASCT/CC+R maintenance were performed. We calculated the odds ratio (ORs) with 95% confidence intervals (CIs), as measure of association between the upfront and rescue therapy (MEL200-ASCT vs CC+R followed by rescue ASCT) with the 4-year risk of second progression/death (PFS2) and death (OS).
Results
In the pooled analysis, 268 patients were randomized to MEL200-ASCT and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 in comparison with CC+R (median 42 vs 24 months, HR 0.53; P<0.001), with a significant advantage in all the subgroups analyzed. In patients with R-ISS Stage I the 4-year PFS1 was 53% with MEL200-ASCT vs 36% with CC+R; in patients with R-ISS Stage II/III the 4-year PFS1 was 41% with MEL200-ASCT vs 23% with CC+R. 134 MEL200-ASCT patients and 176 CC+R patients experienced first progression. 125 patients in the MEL200-ASCT group and 174 in the CC+R group received second-line therapy. MEL200-ASCT significantly prolonged PFS2 in comparison with CC+R (4-year PFS2: 71% vs 54%, HR 0.53, p<0.001). The long-term advantage of MEL200-ASCT was evident in good and bad prognosis patients: in patients with R-ISS Stage I, the 4-year PFS2 was 83% with MEL200-ASCT vs 71% with CC+R; in patients with R-ISS Stage II/III the 4-year PFS2 was 67% with MEL200-ASCT and 48% with CC+R. The PFS1 and PFS2 advantage translated into a significant OS benefit for patients randomized to MEL200-ASCT in comparison with CC+R (4-year OS: 84% vs 70%, HR 0.51, P<0.001). Subgroup analyses of OS were limited by a lower number of events but the advantage with MEL200-ASCT was still evident in most of the subgroups analyzed. At data cut off, in the MEL200-ASCT group, 9% of patients received again ASCT, 68% bortezomib, 16% immunomodulatory agents (IMIDs), 7% other therapies. In the CC+R group, ASCT was recommended but not mandatory at relapse, and the choice of therapy was based on patient’s will and physician discretion according to patient eligibility to ASCT: 53% of patients received ASCT, 38% bortezomib regimens, 6% IMIDs, and 3% other therapies. Upfront ASCT regardless of salvage therapy significantly reduced the risk of second progression/death (OR 0.31; P<0.001) and death (OR 0.41; P=0.003) at 4 years in comparison with CC+R followed by salvage ASCT.
Conclusion
MEL200-ASCT significantly improved PFS1, PFS2 and OS in comparison with CC+R in good and bad prognosis patients. Upfront ASCT significantly reduced the risk of death in comparison with CC+R and salvage ASCT. These data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.
Session topic: New agents for Myeloma treatment
Keyword(s): Chemotherapy, Imids, Multiple myeloma, Transplant
Abstract: S104
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 12:30 - 12:45
Location: Hall A1
Background
In patients with newly diagnosed myeloma, upfront Melphalan 200 mg/m2 followed by ASCT (MEL200-ASCT) prolongs progression-free survival-1 (PFS1) in comparison with chemotherapy plus lenalidomide (CC+R) but ASCT as salvage therapy at first relapse may still effectively rescue patients who did not receive upfront ASCT.
Aims
The primary aim was to evaluate the long-term benefit of upfront ASCT vs CC+R, including the impact of MEL200-ASCT vs CC+R in specific subgroups of patients with different prognostic features. The secondary aim was to evaluate the efficacy of salvage ASCT in patients receiving upfront CC+R.
Methods
We performed an individual patient data meta-analysis of patients enrolled in 2 phase III trials (RV-MM-209 and EMN-441) that randomized patients to MEL200-ASCT vs CC+R. Primary endpoints were PFS1, PFS2, overall survival (OS). Subgroup analyses according to baseline features, protocol and post MEL200-ASCT/CC+R maintenance were performed. We calculated the odds ratio (ORs) with 95% confidence intervals (CIs), as measure of association between the upfront and rescue therapy (MEL200-ASCT vs CC+R followed by rescue ASCT) with the 4-year risk of second progression/death (PFS2) and death (OS).
Results
In the pooled analysis, 268 patients were randomized to MEL200-ASCT and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 in comparison with CC+R (median 42 vs 24 months, HR 0.53; P<0.001), with a significant advantage in all the subgroups analyzed. In patients with R-ISS Stage I the 4-year PFS1 was 53% with MEL200-ASCT vs 36% with CC+R; in patients with R-ISS Stage II/III the 4-year PFS1 was 41% with MEL200-ASCT vs 23% with CC+R. 134 MEL200-ASCT patients and 176 CC+R patients experienced first progression. 125 patients in the MEL200-ASCT group and 174 in the CC+R group received second-line therapy. MEL200-ASCT significantly prolonged PFS2 in comparison with CC+R (4-year PFS2: 71% vs 54%, HR 0.53, p<0.001). The long-term advantage of MEL200-ASCT was evident in good and bad prognosis patients: in patients with R-ISS Stage I, the 4-year PFS2 was 83% with MEL200-ASCT vs 71% with CC+R; in patients with R-ISS Stage II/III the 4-year PFS2 was 67% with MEL200-ASCT and 48% with CC+R. The PFS1 and PFS2 advantage translated into a significant OS benefit for patients randomized to MEL200-ASCT in comparison with CC+R (4-year OS: 84% vs 70%, HR 0.51, P<0.001). Subgroup analyses of OS were limited by a lower number of events but the advantage with MEL200-ASCT was still evident in most of the subgroups analyzed. At data cut off, in the MEL200-ASCT group, 9% of patients received again ASCT, 68% bortezomib, 16% immunomodulatory agents (IMIDs), 7% other therapies. In the CC+R group, ASCT was recommended but not mandatory at relapse, and the choice of therapy was based on patient’s will and physician discretion according to patient eligibility to ASCT: 53% of patients received ASCT, 38% bortezomib regimens, 6% IMIDs, and 3% other therapies. Upfront ASCT regardless of salvage therapy significantly reduced the risk of second progression/death (OR 0.31; P<0.001) and death (OR 0.41; P=0.003) at 4 years in comparison with CC+R followed by salvage ASCT.
Conclusion
MEL200-ASCT significantly improved PFS1, PFS2 and OS in comparison with CC+R in good and bad prognosis patients. Upfront ASCT significantly reduced the risk of death in comparison with CC+R and salvage ASCT. These data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.
Session topic: New agents for Myeloma treatment
Keyword(s): Chemotherapy, Imids, Multiple myeloma, Transplant
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 12:30 - 12:45
Location: Hall A1
Background
In patients with newly diagnosed myeloma, upfront Melphalan 200 mg/m2 followed by ASCT (MEL200-ASCT) prolongs progression-free survival-1 (PFS1) in comparison with chemotherapy plus lenalidomide (CC+R) but ASCT as salvage therapy at first relapse may still effectively rescue patients who did not receive upfront ASCT.
Aims
The primary aim was to evaluate the long-term benefit of upfront ASCT vs CC+R, including the impact of MEL200-ASCT vs CC+R in specific subgroups of patients with different prognostic features. The secondary aim was to evaluate the efficacy of salvage ASCT in patients receiving upfront CC+R.
Methods
We performed an individual patient data meta-analysis of patients enrolled in 2 phase III trials (RV-MM-209 and EMN-441) that randomized patients to MEL200-ASCT vs CC+R. Primary endpoints were PFS1, PFS2, overall survival (OS). Subgroup analyses according to baseline features, protocol and post MEL200-ASCT/CC+R maintenance were performed. We calculated the odds ratio (ORs) with 95% confidence intervals (CIs), as measure of association between the upfront and rescue therapy (MEL200-ASCT vs CC+R followed by rescue ASCT) with the 4-year risk of second progression/death (PFS2) and death (OS).
Results
In the pooled analysis, 268 patients were randomized to MEL200-ASCT and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 in comparison with CC+R (median 42 vs 24 months, HR 0.53; P<0.001), with a significant advantage in all the subgroups analyzed. In patients with R-ISS Stage I the 4-year PFS1 was 53% with MEL200-ASCT vs 36% with CC+R; in patients with R-ISS Stage II/III the 4-year PFS1 was 41% with MEL200-ASCT vs 23% with CC+R. 134 MEL200-ASCT patients and 176 CC+R patients experienced first progression. 125 patients in the MEL200-ASCT group and 174 in the CC+R group received second-line therapy. MEL200-ASCT significantly prolonged PFS2 in comparison with CC+R (4-year PFS2: 71% vs 54%, HR 0.53, p<0.001). The long-term advantage of MEL200-ASCT was evident in good and bad prognosis patients: in patients with R-ISS Stage I, the 4-year PFS2 was 83% with MEL200-ASCT vs 71% with CC+R; in patients with R-ISS Stage II/III the 4-year PFS2 was 67% with MEL200-ASCT and 48% with CC+R. The PFS1 and PFS2 advantage translated into a significant OS benefit for patients randomized to MEL200-ASCT in comparison with CC+R (4-year OS: 84% vs 70%, HR 0.51, P<0.001). Subgroup analyses of OS were limited by a lower number of events but the advantage with MEL200-ASCT was still evident in most of the subgroups analyzed. At data cut off, in the MEL200-ASCT group, 9% of patients received again ASCT, 68% bortezomib, 16% immunomodulatory agents (IMIDs), 7% other therapies. In the CC+R group, ASCT was recommended but not mandatory at relapse, and the choice of therapy was based on patient’s will and physician discretion according to patient eligibility to ASCT: 53% of patients received ASCT, 38% bortezomib regimens, 6% IMIDs, and 3% other therapies. Upfront ASCT regardless of salvage therapy significantly reduced the risk of second progression/death (OR 0.31; P<0.001) and death (OR 0.41; P=0.003) at 4 years in comparison with CC+R followed by salvage ASCT.
Conclusion
MEL200-ASCT significantly improved PFS1, PFS2 and OS in comparison with CC+R in good and bad prognosis patients. Upfront ASCT significantly reduced the risk of death in comparison with CC+R and salvage ASCT. These data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.
Session topic: New agents for Myeloma treatment
Keyword(s): Chemotherapy, Imids, Multiple myeloma, Transplant
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