EFFICACY OF CARFILZOMIB-BASED INDUCTION/CONSOLIDATION WITH OR WITHOUT AUTOLOGOUS TRANSPLANT AND LENALIDOMIDE OR CARFILZOMIB-LENALIDOMIDE MAINTENANCE IN HIGH-RISK PATIENTS IN THE FORTE TRIAL
Author(s): ,
Roberto Mina
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Elena Zamagni
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Francesca Fazio
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Antonio Ledda
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Angelo Palmas
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Sara Aquino
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Paolo de Fabritiis
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Francesca Patriarca
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Daniela Oddolo
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Michele Cea
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Nicola Giuliani
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Antonio Spadano
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Stelvio Ballanti
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Mariella Grasso
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Paolo Corradini
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Michele Cavo
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Mario Boccadoro
Affiliations:
European Myeloma Network,GIMEMA,Italy
,
Pellegrino Musto
Affiliations:
European Myeloma Network,GIMEMA,Italy
Francesca Gay
Affiliations:
European Myeloma Network,GIMEMA,Italy
EHA Library. Mina R. 06/09/21; 324590; S182
Dr. Roberto Mina
Dr. Roberto Mina
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S182

Type: Oral Presentation

Session title: New treatment strategies for newly diagnosed multiple myeloma

Background

Cytogenetic abnormalities (CA) are powerful prognostic factors in multiple myeloma (MM). In the FORTE trial, carfilzomib-lenalidomide-dexamethasone induction/consolidation with ASCT (KRd_ASCT) significantly improved progression-free survival (PFS) vs KRd without ASCT (KRd12, HR 0.64) or carfilzomib-cyclophosphamide-dexamethasone plus ASCT (KCd_ASCT, HR 0.53). KR maintenance significantly improved PFS vs R (HR 0.63).

Aims

The primary aim of this analysis was the impact of treatment on PFS and 1-year sustained MRD negativity (1y-MRD neg) rates according to patient (pt) risk.

Methods

Newly diagnosed MM pts were randomized to KRd_ASCT vs KCd_ASCT vs KRd12 and, thereafter, to KR vs R maintenance. Subgroup analyses according to FISH assessed the impact of each single high-risk (HiR) CA [del17p, t(4;14), t(14;16), del1p and 1q gain (3 copies) or amp1q (≥4 copies)] and that of combined HiR CA, defining HiR by the presence of ≥1 HiR CA and double hit (DH) by the presence of ≥2 HiR CA. Standard risk (SR) was defined by the absence of all the CA.

Results

396 out of 474 enrolled pts were included in the analysis with complete FISH data: 243 HiR, 105 DH and 153 SR. Among HiR pts, 60 had del17p, 65 t(4;14), 20 t(14;16), 44 del1p, 126 1q gain and 49 amp1q.


SR pts benefited from intensification with KRd_ASCT vs KRd12 (HR 0.47, p=0.05) and KCd_ASCT (HR 0.38, p=0.01), with a 4-year PFS of 80%, 67% and 57%, respectively. In the overall HiR population, KRd_ASCT improved PFS vs KRd12 (HR 0.6, p=0.04) and KCd_ASCT (HR 0.57, p=0.01), with a 4-year PFS of 62%, 45% and 45%, respectively. The advantage with KRd_ASCT vs KRd12 (HR 0.53, p=0.07) and KCd_ASCT (HR 0.49; p=0.03) was also observed in DH pts (4-year PFS 55%, 31% and 33%, respectively). Analyses by single CA were limited by the small number of pts in each subgroup, but a PFS benefit from KRd_ASCT vs KRd12 was observed in pts with del17p (HR 0.61, p=0.3), t(4;14) (HR 0.59, p=0.2) and 1q gain (HR 0.45, p=0.02), consistently with the overall population. In pts with del1p, KRd_ASCT (HR 0.24, p=0.06) and KRd12 (HR 0.33, p=0.09) showed superiority over KCd_ASCT, while amp1q pts had the worst outcome regardless of treatment (KRd_ASCT vs KCd_ASCT, HR 1.16, p=0.73; KRd12 vs KCd_ASCT, HR 1.34, p=0.45).


KRd_ASCT induced similar 1y-MRD neg rates in SR (50%), HiR (50%) and DH (47%) pts. Lower 1y-MRD neg rates were observed with KRd12 vs KRd_ASCT. With KRd12, 1y-MRD neg rates were similar in SR (36%) and HiR (39%) but lower in DH (25%) pts; with KCd_ASCT, HiR (48% vs 29%, p=0.04) and DH (48% vs 17%, p=0.03) pts had significantly lower 1y-MRD neg rates than SR pts. Importantly, 1y-MRD neg pts showed a similar 4-year PFS regardless of risk status (SR, 87%, HiR 87%, DH 83%) and treatment arm.


KR improved PFS vs R in SR (3-year PFS 90% vs 73%, HR 0.42, p=0.06), HiR (3-year PFS 69% vs 56%, HR 0.6, p=0.04) and DH pts (3-year PFS 67% vs 42%, HR 0.53, p=0.1). Despite the small subgroups, a benefit from KR vs R was observed in pts with del17p (HR 0.59, p=0.37), t(4;14) (HR 0.59, p=0.3), 1q gain (HR 0.54, p=0.07) and del1p (HR 0.23, p=0.08), while amp1q pts showed the worst outcome and no benefit from KR vs R (HR 0.83, p=0.7).

Conclusion

KRd_ASCT and KR maintenance are highly effective in SR, HiR and DH pts, with impressive 1y-MRD neg rates (KRd_ASCT: HiR 50%, DH 47%), 4-year PFS from diagnosis (KRd_ASCT: HiR 62%, DH 55%) and 3-year PFS from maintenance (KR: HiR 69%, DH 67%), thus supporting their use in HiR pts, who represent an unmet medical need. Achieving 1y-MRD neg mitigated the higher risk of progression/death in HiR and DH pts, as compared to SR pts.

Keyword(s): High risk, Minimal residual disease (MRD), Multiple myeloma, Phase II

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S182

Type: Oral Presentation

Session title: New treatment strategies for newly diagnosed multiple myeloma

Background

Cytogenetic abnormalities (CA) are powerful prognostic factors in multiple myeloma (MM). In the FORTE trial, carfilzomib-lenalidomide-dexamethasone induction/consolidation with ASCT (KRd_ASCT) significantly improved progression-free survival (PFS) vs KRd without ASCT (KRd12, HR 0.64) or carfilzomib-cyclophosphamide-dexamethasone plus ASCT (KCd_ASCT, HR 0.53). KR maintenance significantly improved PFS vs R (HR 0.63).

Aims

The primary aim of this analysis was the impact of treatment on PFS and 1-year sustained MRD negativity (1y-MRD neg) rates according to patient (pt) risk.

Methods

Newly diagnosed MM pts were randomized to KRd_ASCT vs KCd_ASCT vs KRd12 and, thereafter, to KR vs R maintenance. Subgroup analyses according to FISH assessed the impact of each single high-risk (HiR) CA [del17p, t(4;14), t(14;16), del1p and 1q gain (3 copies) or amp1q (≥4 copies)] and that of combined HiR CA, defining HiR by the presence of ≥1 HiR CA and double hit (DH) by the presence of ≥2 HiR CA. Standard risk (SR) was defined by the absence of all the CA.

Results

396 out of 474 enrolled pts were included in the analysis with complete FISH data: 243 HiR, 105 DH and 153 SR. Among HiR pts, 60 had del17p, 65 t(4;14), 20 t(14;16), 44 del1p, 126 1q gain and 49 amp1q.


SR pts benefited from intensification with KRd_ASCT vs KRd12 (HR 0.47, p=0.05) and KCd_ASCT (HR 0.38, p=0.01), with a 4-year PFS of 80%, 67% and 57%, respectively. In the overall HiR population, KRd_ASCT improved PFS vs KRd12 (HR 0.6, p=0.04) and KCd_ASCT (HR 0.57, p=0.01), with a 4-year PFS of 62%, 45% and 45%, respectively. The advantage with KRd_ASCT vs KRd12 (HR 0.53, p=0.07) and KCd_ASCT (HR 0.49; p=0.03) was also observed in DH pts (4-year PFS 55%, 31% and 33%, respectively). Analyses by single CA were limited by the small number of pts in each subgroup, but a PFS benefit from KRd_ASCT vs KRd12 was observed in pts with del17p (HR 0.61, p=0.3), t(4;14) (HR 0.59, p=0.2) and 1q gain (HR 0.45, p=0.02), consistently with the overall population. In pts with del1p, KRd_ASCT (HR 0.24, p=0.06) and KRd12 (HR 0.33, p=0.09) showed superiority over KCd_ASCT, while amp1q pts had the worst outcome regardless of treatment (KRd_ASCT vs KCd_ASCT, HR 1.16, p=0.73; KRd12 vs KCd_ASCT, HR 1.34, p=0.45).


KRd_ASCT induced similar 1y-MRD neg rates in SR (50%), HiR (50%) and DH (47%) pts. Lower 1y-MRD neg rates were observed with KRd12 vs KRd_ASCT. With KRd12, 1y-MRD neg rates were similar in SR (36%) and HiR (39%) but lower in DH (25%) pts; with KCd_ASCT, HiR (48% vs 29%, p=0.04) and DH (48% vs 17%, p=0.03) pts had significantly lower 1y-MRD neg rates than SR pts. Importantly, 1y-MRD neg pts showed a similar 4-year PFS regardless of risk status (SR, 87%, HiR 87%, DH 83%) and treatment arm.


KR improved PFS vs R in SR (3-year PFS 90% vs 73%, HR 0.42, p=0.06), HiR (3-year PFS 69% vs 56%, HR 0.6, p=0.04) and DH pts (3-year PFS 67% vs 42%, HR 0.53, p=0.1). Despite the small subgroups, a benefit from KR vs R was observed in pts with del17p (HR 0.59, p=0.37), t(4;14) (HR 0.59, p=0.3), 1q gain (HR 0.54, p=0.07) and del1p (HR 0.23, p=0.08), while amp1q pts showed the worst outcome and no benefit from KR vs R (HR 0.83, p=0.7).

Conclusion

KRd_ASCT and KR maintenance are highly effective in SR, HiR and DH pts, with impressive 1y-MRD neg rates (KRd_ASCT: HiR 50%, DH 47%), 4-year PFS from diagnosis (KRd_ASCT: HiR 62%, DH 55%) and 3-year PFS from maintenance (KR: HiR 69%, DH 67%), thus supporting their use in HiR pts, who represent an unmet medical need. Achieving 1y-MRD neg mitigated the higher risk of progression/death in HiR and DH pts, as compared to SR pts.

Keyword(s): High risk, Minimal residual disease (MRD), Multiple myeloma, Phase II

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