IMPACT OF BASELINE RENAL FUNCTION ON EFFICACY AND SAFETY OF DARATUMUMAB PLUS BORTEZOMIB-MELPHALAN-PREDNISONE (VMP) IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS INELIGIBLE FOR TRANSPLANTATION (ALCYONE)
Author(s): ,
Michele Cavo
Affiliations:
"Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna,Bologna,Italy
,
Meletios A. Dimopoulos
Affiliations:
National and Kapodistrian University of Athens,Athens,Greece
,
Jesus San-Miguel
Affiliations:
Clínica Universidad de Navarra-CIMA, IDISNA, CIBERONC,Pamplona,Spain
,
Andrzej Jakubowiak
Affiliations:
University of Chicago Medical Center,Chicago, IL,United States
,
Kenshi Suzuki
Affiliations:
Japanese Red Cross Medical Center, Department of Hematology,Tokyo,Japan
,
Sung-Soo Yoon
Affiliations:
Department of Internal Medicine, Seoul National University College of Medicine,Seoul,Korea, Republic Of
,
Mark Cook
Affiliations:
University Hospitals Birmingham NHS Trust,Birmingham,United Kingdom
,
Mario Boccadoro
Affiliations:
Myeloma Unit, Division of Hematology, University of Torino,Torino,Italy
,
P. Joy Ho
Affiliations:
Institute of Haematology, Royal Prince Alfred Hospital,Camperdown, NSW,Australia
,
Ludek Pour
Affiliations:
University Hospital Brno,Brno,Czech Republic
,
Stefan Knop
Affiliations:
Würzburg University Medical Center,Würzburg,Germany
,
Chantal Doyen
Affiliations:
Université catholique de Louvain (UcL) CHU UCL Namur,Yvoir,Belgium
,
Andre Crepaldi
Affiliations:
Clinica de Tratamento E,Cuiaba,Brazil
,
Tamas Masszi
Affiliations:
Department of Haematology and Stem Cell Transplantation, St László Hospital, 3rd Department of Internal Medicine, Semmelweis University,Budapest,Hungary
,
Joan Blade
Affiliations:
Servei d'Hematologia, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona,Barcelona,Spain
,
Jianping Wang
Affiliations:
Janssen Research & Development,Raritan, NJ,United States
,
Susan Wroblewski
Affiliations:
Janssen Research & Development,Spring House, PA,United States
,
William Deraedt
Affiliations:
Janssen Research & Development,Beerse,Belgium
,
Ming Qi
Affiliations:
Janssen Research & Development,Spring House, PA,United States
Maria-Victoria Mateos
Affiliations:
University Hospital of Salamanca/IBSAL,Salamanca,Spain
EHA Learning Center. Cavo M. Jun 15, 2018; 215033
Prof. Michele Cavo
Prof. Michele Cavo

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Abstract
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Abstract: PF583

Type: Poster Presentation

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

Location: Poster area

Background
In the phase 3 ALCYONE study, daratumumab (D) in combination with VMP (D-VMP) prolonged progression-free survival versus VMP alone, and exhibited favorable tolerability in patients with newly diagnosed multiple myeloma.

Aims
We conducted a subgroup analysis of the efficacy and safety of D-VMP versus VMP according to baseline creatinine clearance (CrCl; ≤60 mL/min [moderately impaired] and >60 mL/min).

Methods
Randomized patients were ineligible for high-dose chemotherapy with autologous stem cell transplantation and had baseline CrCl ≥40 mL/min. Up to nine 6-week VMP cycles (V 1.3 mg/m2 subcutaneously on Days 1, 4, 8, 11, 22, 25, 29, 32 in Cycle 1 and Days 1, 8, 22, 29 in Cycles 2-9; M 9 mg/m2 orally and P 60 mg/m2 orally on Days 1-4 in Cycles 1-9) with or without D (16 mg/kg intravenously weekly for Cycle 1, every 3 weeks for Cycles 2-9, and every 4 weeks for Cycles 10+ [post VMP-treatment phase] until progression) were received. Minimal residual disease at 10–5 threshold was evaluated using clonoSEQ® (Adaptive Biotechnologies).

Results
Among 706 (350 D-VMP; 356 VMP) randomized patients, 295 (150 D-VMP; 145 VMP) patients had baseline CrCl ≤60 mL/min and 411 (200 D-VMP; 211 VMP) patients had baseline CrCl >60 mL/min. For D-VMP vs VMP, the median duration of study treatment was 15.3 months vs 12.0 months for the ≤60 mL/min subgroup and 14.5 months vs 12.0 months for >60 mL/min subgroup, respectively.

D-VMP prolonged progression-free survival versus VMP in ≤60 mL/min (median not reached [NR] vs 16.9 months; hazard ratio [HR] 0.36; 95% confidence interval [CI] 0.24-0.56) and >60 mL/min (median NR vs 18.3 months; HR 0.63; 95% CI 0.45-0.88) subgroups after median follow-up of 16.5 months. Overall response rate benefit was maintained for D-VMP vs VMP in the ≤60 mL/min (89% vs 73%; ≥complete response [CR]: 43% vs 24%) and >60 mL/min (92% vs 74%; ≥CR: 43% vs 25%) subgroups. Similar findings were observed with minimal residual disease-negative rates in the ≤60 mL/min (25% vs 8%; odds ratio [OR] 4.13; 95% CI 2.02-8.46) and >60 mL/min (20% vs 5%; OR 4.55; 95% CI 2.26-9.14) subgroups.

Safety findings for D-VMP versus VMP are summarized in the Table. In the ≤60 mL/min and >60 mL/min subgroups, infusion reactions were observed in 27% (Grade 3/4: 5%/0.7%) and 29% (Grade 3/4: 4%/0.5%), respectively.

 

 

CrCl ≤60 mL/min

CrCl >60 mL/min

Grade 3/4, %

D-VMP 

VMP 

D-VMP 

VMP 

Most common (≥10%) treatment-emergent adverse events

 

 

 

 

   Neutropenia

47

38

35

39

   Thrombocytopenia

43

42

28

34

   Anemia

21

29

12

13

   Pneumonia

15

6

9

2

Peripheral sensory neuropathy

2

4

1

4

 

Conclusion
D in combination with VMP prolongs progression-free survival, induces deep responses, and demonstrates acceptable tolerability regardless of baseline renal function. NCT02195479.

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

Keyword(s): Phase III, Renal

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