SINGLE AGENT CARFILZOMIB PROLONGS PFS FOLLOWING TRIPLET THERAPY WITH CYCLOPHOSPHAMIDE & DEXAMETHASONE FOR FIRST RELAPSE/PRIMARY REFRACTORY MULTIPLE MYELOMA: PHASE 2 MUKFIVE STUDY, SECOND ANALYSIS
Author(s): ,
Kwee Yong
Affiliations:
Haematology,UNIVERSITY COLLEGE LONDON,London,United Kingdom
,
Samantha Hinsley
Affiliations:
Clinical Trials Research Unit,Leeds University,Leeds,United Kingdom
,
Debbie Sherratt
Affiliations:
Clinical Trials Research Unit,Leeds University,Leeds,United Kingdom
,
Sarah Brown
Affiliations:
Clinical Trials Research Unit,Leeds University,Leeds,United Kingdom
,
Louise Flanagan
Affiliations:
Clinical Trials Research Unit,Leeds University,Leeds,United Kingdom
,
Catherine Williams
Affiliations:
Haematology,Nottingham University Hospitals,Nottingham,United Kingdom
,
Jamie Cavenagh
Affiliations:
Haematology,St. Bartholomew's Hospital,London,United Kingdom
,
Martin Kaiser
Affiliations:
Molecular Pathology,Institute of Cancer Research,London,United Kingdom
,
Neil Rabin
Affiliations:
Haematology,University College London Hospitals,London,United Kingdom
,
Karthik Ramasamy
Affiliations:
Haematology,University of Oxford,Oxford,United Kingdom
,
Mamta Garg
Affiliations:
Haematology,Leicester Royal Infirmary,Leicester,United Kingdom
,
Holger Auner
Affiliations:
Haematology,Imperial College London,London,United Kingdom
,
Stephen Hawkins
Affiliations:
Cancer Centre,Royal Liverpool University Hospital,Liverpool,United Kingdom
,
Ceri Bygrave
Affiliations:
Haematology,University Hospital Wales,Cardiff,United Kingdom
,
Ruth De Tute
Affiliations:
Haematology Malignancy Diagnostic Service,Leeds University Hospital,Leeds,United Kingdom
,
Gareth Morgan
Affiliations:
Myeloma Institute,University of Arkansas,Little Rock,United States
,
Faith Davies
Affiliations:
Myeloma Institute,University of Arkansas,Little Rock,United States
Roger Owen
Affiliations:
Haematology Malignancy Diagnostic Service,University of Leeds,Leeds,United Kingdom
EHA Library. Yong K. Jun 15, 2018; 215005; PF554
Prof. Kwee Yong
Prof. Kwee Yong
Contributions
Abstract

Abstract: PF554

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Background
Carfilzomib (CFZ) is licensed for use in relapsed/refractory (RR) multiple myeloma (MM).  In the ENDEAVOR study, carfilzomib was combined with dexamethasone for extended therapy, leading to superior progression-free and overall survival (PFS, OS) when compared with bortezomib and dexamethasone. Today, triplet regimens are standard of care, but administering a triplet regimen indefinitely may be challenging. 

Aims
The MUKfive phase 2 study compared safety and activity of KCD to bortezomib, cyclophosphamide and dexamethasone (VCD), as fixed duration therapy for patients at first relapse, or refractory to one prior line. The study also compared activity and safety of maintenance CFZ vs observation after KCD.

Methods
Patients were randomized (R1) in a 2:1 ratio in favor of KCD. Patients in the KCD arm with ≥SD after 6 cycles of KCD were randomized (R2) 1:1 to receive maintenance CFZ or observation. Minimisation factors were response to initial treatment (PR,MR,SD vs VGPR,CR) and prior ASCT. There was no maintenance in the VCD arm. See figure for regimens. Co-primary endpoints were ≥VGPR rate at 24 weeks post R1 (non-inferiority (NI)), and PFS from R2.

Results
300 patients were randomized, 201 KCD and 99 VCD. Patient and disease features were balanced between arms. First primary endpoint, ≥VGPR at 24 weeks was KCD 40.2%, VCD 31.9% (NI), ORR 84.0% and 68.1% (p=0.0014, superior). 141 patients were eligible for R2, 69 allocated to maintenance CFZ. Arms were balanced for response (≥VGPR:CFZ 58.0%,observation 54.2%,) ECOG, ISS, MRD status (MRD-neg: CFZ 11.6%, observation 13.9%) at end of initial treatment. Median follow-up for patients from R2 was 10.5m (0.9-31.3): 44.3% of patients completed 6 cycles CFZ maintenance, 18% completed 18 cycles. 82.1% of patients had a dose modification, but 88.7% of all cycles were received on time. Median PFS from R2 for CFZ was 11.9m vs 5.6m observation (HR 0.59, p=0.009). Safety was as in table 1. AE’s were mild, most were 

Table 1. Safety

Maintenance

Observation

Reasons for stopping treatment

Disease progression 65.6%, completed treatment 18.0%, toxicity 4.9%, withdrew consent 6.6%

 

Patients in safety population

67

74

SAEs: n patients | n events

24/67 (35.8%) | 34 (15 treatment related)

6/74 (8.1%) | 6

SAE types; I=Infections, C=Cardiac

I: 18/34 (52.9%); C: 1/34 (2.9%)

I: 1/6 (16.7%); C: 0

SAEs resulting in death

0

1 (16.7%)

Conclusion
Maintenance with single agent CFZ prolongs PFS after triplet therapy with cyclophosphamide and dexamethasone for MM at first relapse or primary refractory to one line. PFS for patients receiving KCD triplet for 6 cycles followed by maintenance CFZ for up to 18 months approximates 18 months, indicating that it is possible to attenuate regimen intensity following initial treatment with triplet regimen while maintaining disease control when using CFZ in the relapse setting. 

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

Keyword(s): Maintenance, Myeloma, Relapse

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