POST-TRANSPLANT CARFILZOMIB (KYPROLIS
(Abstract release date: 05/21/15)
EHA Library. J. Jakubowiak A. 06/14/15; 103224; S787
Disclosure(s): The University of ChicagoHematology/Oncology
Andrzej J. Jakubowiak
Contributions
Contributions
Abstract
Abstract: S787
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 08:30 to 14.06.2015 08:45
Location: Room A2+3
Background
In a previous phase 1/2 study, extended treatment for 24 months with KRd provided a high rate of stringent complete response (sCR) of 55% and durable disease control with a 3-year progression-free survival (PFS) of 79% and overall survival (OS) of 96% after extended treatment (Jakubowiak et al. Blood 2012; Jasielec et al. ASH 2013). In this Phase 2 study we evaluate post-transplant extended treatment with KRd in NDMM (NCT01816971).
Aims
To assess the efficacy and tolerability of extended post-transplant treatment with KRd in NDMM pts who have received KRd induction and ASCT.
Methods
Pts with symptomatic NDMM per IMWG criteria and transplant candidates were eligible for enrollment. After 4 cycles of KRd induction and ASCT, pts received KRd consolidation treatment (70—90 days post-transplant) as 28-day cycles for 4 cycles: CFZ 36mg/m2 IV on Days 1, 2, 8, 9, 15, 16; LEN PO Days 1-21 starting at 15mg with option to escalate after 1 cycle of consolidation; DEX PO 20mg Days 1, 8, 15, 22. After consolidation, KRd was given for additional 10 maintenance cycles, with modified CFZ schedule on Days 1, 2, 15, 16. LEN single-agent was recommended off protocol at best tolerated dose after KRd maintenance. Dose modifications were permitted to manage toxicities. The primary endpoint was sCR rate at the end of Cycle 8; an improvement of sCR from 30%, the rate observed at the end of 8 cycles without transplant, to 50% in this study will be considered promising for strategy of combining KRd with transplant.
Results
As of Feb 1, 2015, 28 of a total 55 enrolled pts have completed at least 1 cycle of KRd consolidation: 25 pts have completed KRd consolidation and initiated maintenance; 7 pts have completed KRd maintenance and initiated LEN single-agent off protocol. After transplant prior to the initiation of KRd consolidation, ≥VGPR was 96%, ≥near CR (nCR) was 46%, and sCR was 29%. After 4 cycles of consolidation, ≥VGPR was 100%, ≥nCR was 88% and sCR was 72%. The rate of negative minimal residual disease by 9-color flow cytometry at the end of 8 cycles was 88%. Responses deepened in 25 pts treated beyond at least 4 cycles of KRd consolidation with an additional 1 pt converting to nCR and 3 to sCR, resulting in ≥nCR 96% and sCR 84%. After a median follow-up of 14 months from the start of the KRd treatment (range 8-24), all 28 pts were alive and progression free. There were no new or unexpected toxicities post-transplant compared to the referenced above phase 1/2 trial of KRd without transplant. Enrollment continues with a target of 70 pts; 55 have been enrolled and updated results of pts receiving at least one cycle post-ASCT will be reported during the meeting.
Summary
Based on this analysis, extended post-transplant treatment with KRd can be considered for future evaluation in pts who have received induction regimens other than KRd. The preliminary data suggest that KRd with transplant has high efficacy compared to standard single-agent maintenance therapy post-transplant.
Keyword(s): Autologous bone marrow transplant, Consolidation, Myeloma
Session topic: Multiple myeloma: Clinical studies 3
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 08:30 to 14.06.2015 08:45
Location: Room A2+3
Background
In a previous phase 1/2 study, extended treatment for 24 months with KRd provided a high rate of stringent complete response (sCR) of 55% and durable disease control with a 3-year progression-free survival (PFS) of 79% and overall survival (OS) of 96% after extended treatment (Jakubowiak et al. Blood 2012; Jasielec et al. ASH 2013). In this Phase 2 study we evaluate post-transplant extended treatment with KRd in NDMM (NCT01816971).
Aims
To assess the efficacy and tolerability of extended post-transplant treatment with KRd in NDMM pts who have received KRd induction and ASCT.
Methods
Pts with symptomatic NDMM per IMWG criteria and transplant candidates were eligible for enrollment. After 4 cycles of KRd induction and ASCT, pts received KRd consolidation treatment (70—90 days post-transplant) as 28-day cycles for 4 cycles: CFZ 36mg/m2 IV on Days 1, 2, 8, 9, 15, 16; LEN PO Days 1-21 starting at 15mg with option to escalate after 1 cycle of consolidation; DEX PO 20mg Days 1, 8, 15, 22. After consolidation, KRd was given for additional 10 maintenance cycles, with modified CFZ schedule on Days 1, 2, 15, 16. LEN single-agent was recommended off protocol at best tolerated dose after KRd maintenance. Dose modifications were permitted to manage toxicities. The primary endpoint was sCR rate at the end of Cycle 8; an improvement of sCR from 30%, the rate observed at the end of 8 cycles without transplant, to 50% in this study will be considered promising for strategy of combining KRd with transplant.
Results
As of Feb 1, 2015, 28 of a total 55 enrolled pts have completed at least 1 cycle of KRd consolidation: 25 pts have completed KRd consolidation and initiated maintenance; 7 pts have completed KRd maintenance and initiated LEN single-agent off protocol. After transplant prior to the initiation of KRd consolidation, ≥VGPR was 96%, ≥near CR (nCR) was 46%, and sCR was 29%. After 4 cycles of consolidation, ≥VGPR was 100%, ≥nCR was 88% and sCR was 72%. The rate of negative minimal residual disease by 9-color flow cytometry at the end of 8 cycles was 88%. Responses deepened in 25 pts treated beyond at least 4 cycles of KRd consolidation with an additional 1 pt converting to nCR and 3 to sCR, resulting in ≥nCR 96% and sCR 84%. After a median follow-up of 14 months from the start of the KRd treatment (range 8-24), all 28 pts were alive and progression free. There were no new or unexpected toxicities post-transplant compared to the referenced above phase 1/2 trial of KRd without transplant. Enrollment continues with a target of 70 pts; 55 have been enrolled and updated results of pts receiving at least one cycle post-ASCT will be reported during the meeting.
Summary
Based on this analysis, extended post-transplant treatment with KRd can be considered for future evaluation in pts who have received induction regimens other than KRd. The preliminary data suggest that KRd with transplant has high efficacy compared to standard single-agent maintenance therapy post-transplant.
Keyword(s): Autologous bone marrow transplant, Consolidation, Myeloma
Session topic: Multiple myeloma: Clinical studies 3
Abstract: S787
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 08:30 to 14.06.2015 08:45
Location: Room A2+3
Background
In a previous phase 1/2 study, extended treatment for 24 months with KRd provided a high rate of stringent complete response (sCR) of 55% and durable disease control with a 3-year progression-free survival (PFS) of 79% and overall survival (OS) of 96% after extended treatment (Jakubowiak et al. Blood 2012; Jasielec et al. ASH 2013). In this Phase 2 study we evaluate post-transplant extended treatment with KRd in NDMM (NCT01816971).
Aims
To assess the efficacy and tolerability of extended post-transplant treatment with KRd in NDMM pts who have received KRd induction and ASCT.
Methods
Pts with symptomatic NDMM per IMWG criteria and transplant candidates were eligible for enrollment. After 4 cycles of KRd induction and ASCT, pts received KRd consolidation treatment (70—90 days post-transplant) as 28-day cycles for 4 cycles: CFZ 36mg/m2 IV on Days 1, 2, 8, 9, 15, 16; LEN PO Days 1-21 starting at 15mg with option to escalate after 1 cycle of consolidation; DEX PO 20mg Days 1, 8, 15, 22. After consolidation, KRd was given for additional 10 maintenance cycles, with modified CFZ schedule on Days 1, 2, 15, 16. LEN single-agent was recommended off protocol at best tolerated dose after KRd maintenance. Dose modifications were permitted to manage toxicities. The primary endpoint was sCR rate at the end of Cycle 8; an improvement of sCR from 30%, the rate observed at the end of 8 cycles without transplant, to 50% in this study will be considered promising for strategy of combining KRd with transplant.
Results
As of Feb 1, 2015, 28 of a total 55 enrolled pts have completed at least 1 cycle of KRd consolidation: 25 pts have completed KRd consolidation and initiated maintenance; 7 pts have completed KRd maintenance and initiated LEN single-agent off protocol. After transplant prior to the initiation of KRd consolidation, ≥VGPR was 96%, ≥near CR (nCR) was 46%, and sCR was 29%. After 4 cycles of consolidation, ≥VGPR was 100%, ≥nCR was 88% and sCR was 72%. The rate of negative minimal residual disease by 9-color flow cytometry at the end of 8 cycles was 88%. Responses deepened in 25 pts treated beyond at least 4 cycles of KRd consolidation with an additional 1 pt converting to nCR and 3 to sCR, resulting in ≥nCR 96% and sCR 84%. After a median follow-up of 14 months from the start of the KRd treatment (range 8-24), all 28 pts were alive and progression free. There were no new or unexpected toxicities post-transplant compared to the referenced above phase 1/2 trial of KRd without transplant. Enrollment continues with a target of 70 pts; 55 have been enrolled and updated results of pts receiving at least one cycle post-ASCT will be reported during the meeting.
Summary
Based on this analysis, extended post-transplant treatment with KRd can be considered for future evaluation in pts who have received induction regimens other than KRd. The preliminary data suggest that KRd with transplant has high efficacy compared to standard single-agent maintenance therapy post-transplant.
Keyword(s): Autologous bone marrow transplant, Consolidation, Myeloma
Session topic: Multiple myeloma: Clinical studies 3
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 08:30 to 14.06.2015 08:45
Location: Room A2+3
Background
In a previous phase 1/2 study, extended treatment for 24 months with KRd provided a high rate of stringent complete response (sCR) of 55% and durable disease control with a 3-year progression-free survival (PFS) of 79% and overall survival (OS) of 96% after extended treatment (Jakubowiak et al. Blood 2012; Jasielec et al. ASH 2013). In this Phase 2 study we evaluate post-transplant extended treatment with KRd in NDMM (NCT01816971).
Aims
To assess the efficacy and tolerability of extended post-transplant treatment with KRd in NDMM pts who have received KRd induction and ASCT.
Methods
Pts with symptomatic NDMM per IMWG criteria and transplant candidates were eligible for enrollment. After 4 cycles of KRd induction and ASCT, pts received KRd consolidation treatment (70—90 days post-transplant) as 28-day cycles for 4 cycles: CFZ 36mg/m2 IV on Days 1, 2, 8, 9, 15, 16; LEN PO Days 1-21 starting at 15mg with option to escalate after 1 cycle of consolidation; DEX PO 20mg Days 1, 8, 15, 22. After consolidation, KRd was given for additional 10 maintenance cycles, with modified CFZ schedule on Days 1, 2, 15, 16. LEN single-agent was recommended off protocol at best tolerated dose after KRd maintenance. Dose modifications were permitted to manage toxicities. The primary endpoint was sCR rate at the end of Cycle 8; an improvement of sCR from 30%, the rate observed at the end of 8 cycles without transplant, to 50% in this study will be considered promising for strategy of combining KRd with transplant.
Results
As of Feb 1, 2015, 28 of a total 55 enrolled pts have completed at least 1 cycle of KRd consolidation: 25 pts have completed KRd consolidation and initiated maintenance; 7 pts have completed KRd maintenance and initiated LEN single-agent off protocol. After transplant prior to the initiation of KRd consolidation, ≥VGPR was 96%, ≥near CR (nCR) was 46%, and sCR was 29%. After 4 cycles of consolidation, ≥VGPR was 100%, ≥nCR was 88% and sCR was 72%. The rate of negative minimal residual disease by 9-color flow cytometry at the end of 8 cycles was 88%. Responses deepened in 25 pts treated beyond at least 4 cycles of KRd consolidation with an additional 1 pt converting to nCR and 3 to sCR, resulting in ≥nCR 96% and sCR 84%. After a median follow-up of 14 months from the start of the KRd treatment (range 8-24), all 28 pts were alive and progression free. There were no new or unexpected toxicities post-transplant compared to the referenced above phase 1/2 trial of KRd without transplant. Enrollment continues with a target of 70 pts; 55 have been enrolled and updated results of pts receiving at least one cycle post-ASCT will be reported during the meeting.
Summary
Based on this analysis, extended post-transplant treatment with KRd can be considered for future evaluation in pts who have received induction regimens other than KRd. The preliminary data suggest that KRd with transplant has high efficacy compared to standard single-agent maintenance therapy post-transplant.
Keyword(s): Autologous bone marrow transplant, Consolidation, Myeloma
Session topic: Multiple myeloma: Clinical studies 3
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