CARFILZOMIB LENALIDOMIDE DEXAMETHASONE (KRD) WITH OR WITHOUT TRANSPLANTATION IN NEWLY DIAGNOSED MYELOMA (FORTE TRIAL): EFFICACY ACCORDING TO RISK STATUS
Author(s): ,
Francesca Gay
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Chiara Cerrato
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Delia Rota Scalabrini
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Angelo Belotti
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Monica Galli
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Elena Zamagni
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Massimo Offidani
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Paola Omedé
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Federico Monaco
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Patrizia Tosi
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Ombretta Annibali
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Francesco Pisani
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Rossella Troia
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Anna Pascarella
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Felicetto Ferrara
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Michele Cea
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Benedetta Dalla Palma
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Francesca Patriarca
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Sara Aquino
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Angelo Palmas
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Agostina Siniscalchi
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Mariella Grasso
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Antonio Palumbo
Affiliations:
University of Torino,Currently Takeda,Switzerland,Italy
,
Antonio Ledda
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Pellegrino Musto
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
,
Michele Cavo
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
Mario Boccadoro
Affiliations:
GIMEMA,European Myeloma Network - Italy,Italy
EHA Library. Gay F. Jun 15, 2019; 267455; S872
Francesca Gay
Francesca Gay
Contributions
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Abstract

Abstract: S872

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 16:15 - 16:30

Location: Auditorium

Background
High and comparable rates of response and minimal residual disease (MRD) negativity were reported with four 28-day induction cycles of KRd followed by autologous stem-cell transplantation (ASCT) and 4 KRd consolidation (KRd_ASCT_KRd), and with 12 KRd cycles (KRd12) in newly diagnosed myeloma (NDMM) patients. Of note, both regimens were superior to carfilzomib-cyclophosphamide-dexamethasone (KCd) induction followed by ASCT and KCd consolidation (KCd-ASCT-KCd) (Gay F ASH 2018).

Aims
We evaluated the benefit of KRd_ASCT_KRd vs KRd12 in specific subgroups of patients according to their risk status.

Methods
474 NDMM patients ≤65 years were randomized to KRd_ASCT_KRd or KRd12 or KCd_ASCT_KCd. We compared rate of ≥VGPR, ≥CR, sCR, MRD negativity (centralized, second generation flow cytometry, sensitivity 10-5) after consolidation with KRd_ASCT_KRd vs KRd12 in patients with available Revised International Staging System (R-ISS) 1 and R-ISS 2/3. High-risk patients may sometimes respond rapidly, but subsequently relapse early. Therefore, we also analyzed the rate of early relapse (<18 months from randomization) in the two arms. We performed a multivariate logistic regression analysis to evaluate factors predictive of early relapse. 

Results
Median follow-up was 25 months. On intention-to-treat analysis, KRd_ASCT_KRd and KRd12 showed similar rates of ≥VGPR, ≥CR, sCR, MRD negativity in the overall population (Table 1A). Similarly, MRD negativity and response rates in the two treatment arms were comparable in the subgroups of patients with R-ISS Stage 1 and with R-ISS Stage 2/3 (Table 1B). Of note, rate of MRD negativity in high-risk patients was around 50% (Table 1B). In the overall population, early relapses were significantly lower with KRd_ASCT_KRd vs KRd12 (12 patients [8%] vs 26 patients [17%]; P=0.015), mainly related to a significantly lower rate of early relapse in patients with high risk status (R-ISS Stage 2/3) (11 patients [12%] vs 22 patients [23%]; P=0.05, respectively). Very few patients with R-ISS Stage 1 relapsed, with no difference between KRd_ASCT_KRd and KRd12 (0 vs 2 patients). In multivariate regression analysis, patients receiving KRd_ASCT_KRd had a reduced risk of early relapse compared with those treated with KRd12 (OR 0.42; P=0.021); R-ISS Stage 2 (OR 3.6; P=0.001) and R-ISS Stage 3 (OR 4.85; P=0.003) increased the risk of early relapse compared with R-ISS 1.

Table 1A: Overall population

Table 1B: Subgroup analysis

 

KRd_ASCT_KRd

N=158

KRd12

N=157

R-ISS 1

R-ISS 2/3

KRd_ASCT_KRd

N=48

KRd12

N=39

KRd_ASCT_KRd

N=92

KRd12

N=94

 

sCR

44%

43%

46%

49%

39%

38%

≥CR

60%

61%

60%

64%

56%

57%

≥VGPR

89%

87%

92%

79%

86%

86%

MRD negative

58%

54%

69%

62%

51%

47%

Conclusion
KRd-ASCT-KRd and KRd12 were equally effective in inducing high-quality responses, and approximately 50% of high-risk patients achieved MRD negativity. In addition, ASCT proved to be beneficial in high-risk patients, reducing the risk of early relapse.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Myeloma, Transplant

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