IMPROVED EFFICACY AFTER INCORPORATING AUTOLOGOUS STEM CELL TRANSPLANT (ASCT) INTO KRD TREATMENT WITH CARFILZOMIB (CFZ), LENALIDOMIDE (LEN), AND DEXAMETHASONE (DEX) IN NEWLY DIAGNOSED MULTIPLE MYELOMA
(Abstract release date: 05/19/16)
EHA Library. J. Jakubowiak A. 06/10/16; 135134; S101
Andrzej J. Jakubowiak
Contributions
Contributions
Abstract
Abstract: S101
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:45 - 12:00
Location: Hall A1
Background
In a phase 1/2 trial (N=53), extended treatment with KRd without (w/o) ASCT was highly active in newly diagnosed myeloma (NDMM) with stringent complete response (sCR) 55% and 3-year progression-free survival (PFS) 79%.
Aims
In a subsequent phase 2 trial, we are evaluating whether extended KRd can be further improved by incorporating ASCT (KRd+ASCT). We report results from both trials after completion of enrollment into KRd+ASCT and after completion of KRd w/o ASCT (median follow-up [f/u] 4 years) as a historical control.
Methods
Both studies enrolled patients (pts) with NDMM based on similar eligibility criteria except KRd+ASCT excluded transplant ineligible pts. The treatment schemas were generally similar between studies. In KRd+ASCT, pts received: four 28-day cycles of induction with CFZ IV 36 mg/m2 on Days (D) 1-2, 8-9, 15-16 (CFZ 20 mg/m2 for D1-2, C1 only), LEN PO D121 at 25 mg, DEX PO 40 mg/wk; followed by stem cell collection (SCC), melphalan 200 mg/m2 and ASCT; then KRd consolidation (C5-8) using the same doses and schedule except LEN 15 mg in C5 with the option to escalate to prior dose, and DEX reduced to 20 mg/wk; then KRd maintenance (C9-18) using the same doses as in C8 except CFZ on Days 1-2, 15-16 only. In KRd w/o ASCT, transplant-eligible pts underwent SCC after C4 then resumed KRd, and KRd maintenance was longer (C9-24). Both studies recommended single-agent LEN off study. The primary endpoint in KRd+ASCT is sCR at the end of C8. We hypothesized that an improvement of sCR from 30% at the end of C8 (historical KRd w/o ASCT) to >50% (KRd+ASCT) represents added benefit of ASCT with 5% type I error (2 sided) and supports further evaluation. Minimal residual disease (MRD) is evaluated by 10-color multiparameter flow cytometry (MFC, threshold 10-4-10‑5) and by next-generation sequencing (NGS, LymphoSIGHTTM, threshold at 10-6 for MRD negativity).
Results
The current KRd+ASCT study enrolled 76 pts with 72 evaluable. Baseline characteristics were comparable between the KRd+ASCT and KRd w/o ASCT study populations, including median age (59 and 59y) and high-risk IMWG cytogenetics (36% and 33%). In the ongoing KRd+ASCT, 69 pts proceeded to ASCT at data cut-off (Jan 1, 2016), 50 completed KRd consolidation, and 26 KRd maintenance, with remaining pts on treatment, except 1 patient who progressed prior to transplant. At the end of C8, sCR was 72% for KRd+ASCT (n=50) vs 30% for KRd w/o ASCT (n=44) and 88% (n=26) vs 51% (n=41) at the end of C18. At median f/u of 17.8 months, 2-year PFS was 99% for KRd+ASCT vs 92% for KRd w/o ASCT at median f/u of 47.5 months. In KRd+ASCT, MRD by MFC was negative in 94% of pts tested (n=31) at the end of C8 and 95% of pts tested (n=19) at the end of C18. In KRd w/o ASCT, 4-year PFS was 69% overall, 78% in MRD-negative pts vs 60% in positive/unknown pts by MFC, and 100% in pts with MRD negative status by NGS. Updated MRD analyses and outcomes based on MRD status by both MFC and NGS will be presented at the meeting. The types and rates of adverse events (AEs) pre- and post-ASCT were comparable to AEs in KRd w/o ASCT.
Conclusion
Recognizing limitations of cross-study comparisons, KRd+ASCT shows superior outcomes vs historical KRd w/o ASCT, supporting further evaluation in the randomized setting. Both KRd studies compare favorably to other NDMM studies.
Session topic: New agents for Myeloma treatment
Keyword(s): Bone marrow transplant, Clinical trial, Minimal residual disease (MRD), MRD
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:45 - 12:00
Location: Hall A1
Background
In a phase 1/2 trial (N=53), extended treatment with KRd without (w/o) ASCT was highly active in newly diagnosed myeloma (NDMM) with stringent complete response (sCR) 55% and 3-year progression-free survival (PFS) 79%.
Aims
In a subsequent phase 2 trial, we are evaluating whether extended KRd can be further improved by incorporating ASCT (KRd+ASCT). We report results from both trials after completion of enrollment into KRd+ASCT and after completion of KRd w/o ASCT (median follow-up [f/u] 4 years) as a historical control.
Methods
Both studies enrolled patients (pts) with NDMM based on similar eligibility criteria except KRd+ASCT excluded transplant ineligible pts. The treatment schemas were generally similar between studies. In KRd+ASCT, pts received: four 28-day cycles of induction with CFZ IV 36 mg/m2 on Days (D) 1-2, 8-9, 15-16 (CFZ 20 mg/m2 for D1-2, C1 only), LEN PO D121 at 25 mg, DEX PO 40 mg/wk; followed by stem cell collection (SCC), melphalan 200 mg/m2 and ASCT; then KRd consolidation (C5-8) using the same doses and schedule except LEN 15 mg in C5 with the option to escalate to prior dose, and DEX reduced to 20 mg/wk; then KRd maintenance (C9-18) using the same doses as in C8 except CFZ on Days 1-2, 15-16 only. In KRd w/o ASCT, transplant-eligible pts underwent SCC after C4 then resumed KRd, and KRd maintenance was longer (C9-24). Both studies recommended single-agent LEN off study. The primary endpoint in KRd+ASCT is sCR at the end of C8. We hypothesized that an improvement of sCR from 30% at the end of C8 (historical KRd w/o ASCT) to >50% (KRd+ASCT) represents added benefit of ASCT with 5% type I error (2 sided) and supports further evaluation. Minimal residual disease (MRD) is evaluated by 10-color multiparameter flow cytometry (MFC, threshold 10-4-10‑5) and by next-generation sequencing (NGS, LymphoSIGHTTM, threshold at 10-6 for MRD negativity).
Results
The current KRd+ASCT study enrolled 76 pts with 72 evaluable. Baseline characteristics were comparable between the KRd+ASCT and KRd w/o ASCT study populations, including median age (59 and 59y) and high-risk IMWG cytogenetics (36% and 33%). In the ongoing KRd+ASCT, 69 pts proceeded to ASCT at data cut-off (Jan 1, 2016), 50 completed KRd consolidation, and 26 KRd maintenance, with remaining pts on treatment, except 1 patient who progressed prior to transplant. At the end of C8, sCR was 72% for KRd+ASCT (n=50) vs 30% for KRd w/o ASCT (n=44) and 88% (n=26) vs 51% (n=41) at the end of C18. At median f/u of 17.8 months, 2-year PFS was 99% for KRd+ASCT vs 92% for KRd w/o ASCT at median f/u of 47.5 months. In KRd+ASCT, MRD by MFC was negative in 94% of pts tested (n=31) at the end of C8 and 95% of pts tested (n=19) at the end of C18. In KRd w/o ASCT, 4-year PFS was 69% overall, 78% in MRD-negative pts vs 60% in positive/unknown pts by MFC, and 100% in pts with MRD negative status by NGS. Updated MRD analyses and outcomes based on MRD status by both MFC and NGS will be presented at the meeting. The types and rates of adverse events (AEs) pre- and post-ASCT were comparable to AEs in KRd w/o ASCT.
Conclusion
Recognizing limitations of cross-study comparisons, KRd+ASCT shows superior outcomes vs historical KRd w/o ASCT, supporting further evaluation in the randomized setting. Both KRd studies compare favorably to other NDMM studies.
Session topic: New agents for Myeloma treatment
Keyword(s): Bone marrow transplant, Clinical trial, Minimal residual disease (MRD), MRD
Abstract: S101
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:45 - 12:00
Location: Hall A1
Background
In a phase 1/2 trial (N=53), extended treatment with KRd without (w/o) ASCT was highly active in newly diagnosed myeloma (NDMM) with stringent complete response (sCR) 55% and 3-year progression-free survival (PFS) 79%.
Aims
In a subsequent phase 2 trial, we are evaluating whether extended KRd can be further improved by incorporating ASCT (KRd+ASCT). We report results from both trials after completion of enrollment into KRd+ASCT and after completion of KRd w/o ASCT (median follow-up [f/u] 4 years) as a historical control.
Methods
Both studies enrolled patients (pts) with NDMM based on similar eligibility criteria except KRd+ASCT excluded transplant ineligible pts. The treatment schemas were generally similar between studies. In KRd+ASCT, pts received: four 28-day cycles of induction with CFZ IV 36 mg/m2 on Days (D) 1-2, 8-9, 15-16 (CFZ 20 mg/m2 for D1-2, C1 only), LEN PO D121 at 25 mg, DEX PO 40 mg/wk; followed by stem cell collection (SCC), melphalan 200 mg/m2 and ASCT; then KRd consolidation (C5-8) using the same doses and schedule except LEN 15 mg in C5 with the option to escalate to prior dose, and DEX reduced to 20 mg/wk; then KRd maintenance (C9-18) using the same doses as in C8 except CFZ on Days 1-2, 15-16 only. In KRd w/o ASCT, transplant-eligible pts underwent SCC after C4 then resumed KRd, and KRd maintenance was longer (C9-24). Both studies recommended single-agent LEN off study. The primary endpoint in KRd+ASCT is sCR at the end of C8. We hypothesized that an improvement of sCR from 30% at the end of C8 (historical KRd w/o ASCT) to >50% (KRd+ASCT) represents added benefit of ASCT with 5% type I error (2 sided) and supports further evaluation. Minimal residual disease (MRD) is evaluated by 10-color multiparameter flow cytometry (MFC, threshold 10-4-10‑5) and by next-generation sequencing (NGS, LymphoSIGHTTM, threshold at 10-6 for MRD negativity).
Results
The current KRd+ASCT study enrolled 76 pts with 72 evaluable. Baseline characteristics were comparable between the KRd+ASCT and KRd w/o ASCT study populations, including median age (59 and 59y) and high-risk IMWG cytogenetics (36% and 33%). In the ongoing KRd+ASCT, 69 pts proceeded to ASCT at data cut-off (Jan 1, 2016), 50 completed KRd consolidation, and 26 KRd maintenance, with remaining pts on treatment, except 1 patient who progressed prior to transplant. At the end of C8, sCR was 72% for KRd+ASCT (n=50) vs 30% for KRd w/o ASCT (n=44) and 88% (n=26) vs 51% (n=41) at the end of C18. At median f/u of 17.8 months, 2-year PFS was 99% for KRd+ASCT vs 92% for KRd w/o ASCT at median f/u of 47.5 months. In KRd+ASCT, MRD by MFC was negative in 94% of pts tested (n=31) at the end of C8 and 95% of pts tested (n=19) at the end of C18. In KRd w/o ASCT, 4-year PFS was 69% overall, 78% in MRD-negative pts vs 60% in positive/unknown pts by MFC, and 100% in pts with MRD negative status by NGS. Updated MRD analyses and outcomes based on MRD status by both MFC and NGS will be presented at the meeting. The types and rates of adverse events (AEs) pre- and post-ASCT were comparable to AEs in KRd w/o ASCT.
Conclusion
Recognizing limitations of cross-study comparisons, KRd+ASCT shows superior outcomes vs historical KRd w/o ASCT, supporting further evaluation in the randomized setting. Both KRd studies compare favorably to other NDMM studies.
Session topic: New agents for Myeloma treatment
Keyword(s): Bone marrow transplant, Clinical trial, Minimal residual disease (MRD), MRD
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:45 - 12:00
Location: Hall A1
Background
In a phase 1/2 trial (N=53), extended treatment with KRd without (w/o) ASCT was highly active in newly diagnosed myeloma (NDMM) with stringent complete response (sCR) 55% and 3-year progression-free survival (PFS) 79%.
Aims
In a subsequent phase 2 trial, we are evaluating whether extended KRd can be further improved by incorporating ASCT (KRd+ASCT). We report results from both trials after completion of enrollment into KRd+ASCT and after completion of KRd w/o ASCT (median follow-up [f/u] 4 years) as a historical control.
Methods
Both studies enrolled patients (pts) with NDMM based on similar eligibility criteria except KRd+ASCT excluded transplant ineligible pts. The treatment schemas were generally similar between studies. In KRd+ASCT, pts received: four 28-day cycles of induction with CFZ IV 36 mg/m2 on Days (D) 1-2, 8-9, 15-16 (CFZ 20 mg/m2 for D1-2, C1 only), LEN PO D121 at 25 mg, DEX PO 40 mg/wk; followed by stem cell collection (SCC), melphalan 200 mg/m2 and ASCT; then KRd consolidation (C5-8) using the same doses and schedule except LEN 15 mg in C5 with the option to escalate to prior dose, and DEX reduced to 20 mg/wk; then KRd maintenance (C9-18) using the same doses as in C8 except CFZ on Days 1-2, 15-16 only. In KRd w/o ASCT, transplant-eligible pts underwent SCC after C4 then resumed KRd, and KRd maintenance was longer (C9-24). Both studies recommended single-agent LEN off study. The primary endpoint in KRd+ASCT is sCR at the end of C8. We hypothesized that an improvement of sCR from 30% at the end of C8 (historical KRd w/o ASCT) to >50% (KRd+ASCT) represents added benefit of ASCT with 5% type I error (2 sided) and supports further evaluation. Minimal residual disease (MRD) is evaluated by 10-color multiparameter flow cytometry (MFC, threshold 10-4-10‑5) and by next-generation sequencing (NGS, LymphoSIGHTTM, threshold at 10-6 for MRD negativity).
Results
The current KRd+ASCT study enrolled 76 pts with 72 evaluable. Baseline characteristics were comparable between the KRd+ASCT and KRd w/o ASCT study populations, including median age (59 and 59y) and high-risk IMWG cytogenetics (36% and 33%). In the ongoing KRd+ASCT, 69 pts proceeded to ASCT at data cut-off (Jan 1, 2016), 50 completed KRd consolidation, and 26 KRd maintenance, with remaining pts on treatment, except 1 patient who progressed prior to transplant. At the end of C8, sCR was 72% for KRd+ASCT (n=50) vs 30% for KRd w/o ASCT (n=44) and 88% (n=26) vs 51% (n=41) at the end of C18. At median f/u of 17.8 months, 2-year PFS was 99% for KRd+ASCT vs 92% for KRd w/o ASCT at median f/u of 47.5 months. In KRd+ASCT, MRD by MFC was negative in 94% of pts tested (n=31) at the end of C8 and 95% of pts tested (n=19) at the end of C18. In KRd w/o ASCT, 4-year PFS was 69% overall, 78% in MRD-negative pts vs 60% in positive/unknown pts by MFC, and 100% in pts with MRD negative status by NGS. Updated MRD analyses and outcomes based on MRD status by both MFC and NGS will be presented at the meeting. The types and rates of adverse events (AEs) pre- and post-ASCT were comparable to AEs in KRd w/o ASCT.
Conclusion
Recognizing limitations of cross-study comparisons, KRd+ASCT shows superior outcomes vs historical KRd w/o ASCT, supporting further evaluation in the randomized setting. Both KRd studies compare favorably to other NDMM studies.
Session topic: New agents for Myeloma treatment
Keyword(s): Bone marrow transplant, Clinical trial, Minimal residual disease (MRD), MRD
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