Bortezomib as consolidation after high-dose
melphalan and autologous stem cell
transplantation in multiple myeloma:
a Nordic Myeloma Study Group (NMSG)
randomized trial
Ulf-Henrik Mellqvist
Sahlgrenska University Hospital
Gothenburg Sweden
Disclosures
Honoraria: Celgene and Janssen
Study grant: Johnson & Johnson
2
1
Objectives
Primary:
Progression free survival
Secondary:
Response
Overall survival
Toxicity
Quality of life
Study design
Open randomized multicenter study
Initial therapy optional (no bortezomib)
Inclusion from stem cell infusion up to 3 months after ASCT
Randomization 3 months post ASCT
Stratification for age (<60 or 60+ years) and single/double ASCT
2
Bortezomib therapy
Initiated 3 months post ASCT
Standard dose 1.3 mg/m2
Two initial conventional cycles (day 1, 4, 8 and 11),
followed by four cycles of weekly injections for 3 weeks
plus 1 week rest
In total, 20 injections over a period of 21 weeks
No doses were postponed, instead dose reduction to zero
No corticosteroids were added
Patient material
403 included from 2006 until April 2009
4 excluded -
2 non-secreting myeloma
2 not fullfilling diagnostic criteria
399
29 not randomised -17 withdrawn consent
4 neuropathy
4 progressive disease
2 logistic reasons
1 death
370
1 infection
188 Bortezomib
182 Control
3
Toxicity
Hematological:
Neutropenia
Thrombocytopenia
Neurological:
Neuropathic pain
Peripheral sensory neuropathy
Mean neutrophil count
4
Mean neutrophil count
Mean platelet count
5
Mean platelet count
Neuropathic pain
bortezomib
control
count
Maximal grade
6
Neuropathic pain
bortezomib
control
count
Maximal grade
CTC III bortezomib 6 %
control 0.5 %
Peripheral sensory neuropathy
bortezomib
control
count
Maximal grade
7
Peripheral sensory neuropathy
bortezomib
control
count
Maximal grade
CTC III bortezomib 5 %
control 2 %
Feasibility
8
Feasibility
Actually given total dose in relation to planned total dose
Median = 90 %
Mean = 82 %
Response
Bortezomib
After ASCT
Best reported
CR/nCR
20 %
45 %
VGPR
39 %
71 %
Control
After ASCT
Best reported
CR/nCR
21 %
35 %
VGPR
39 %
57 %
9
Response
Bortezomib
After ASCT
Best reported
CR/nCR
20 %
45 %
VGPR
39 %
71 %
Control
After ASCT
Best reported
CR/nCR
21 %
35 %
P<0.05
VGPR
39 %
57 %
Improvement of response
· Bortezomib: 68 patients
51 from PR to VGPR
17 from VGPR to nCR
· Control 42 patients
32 from PR to VGPR
10 from VGPR to nCR
10
Improvement of response
· Bortezomib: 68 patients
51 from PR to VGPR
17 from VGPR to nCR
P<0.05
· Control 42 patients
32 from PR to VGPR
10 from VGPR to nCR
Progression free survival
27 mo
bortezomib
control
p=0.037
20 mo
11
Progression free survival
< VGPR after ASCT
VGPR after ASCT
bortezomib
bortezomib
control
control
p=0.04
p=0.8
Progression free survival
All patients
VGPR directly after ASCT vs later
After ASCT
later response
p=0.4
24
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Overall survival
No significant difference in OS after a
median follow up of 27 months.
Estimated OS at this time point is
approximately 87 % for both groups.
Conclusions I
Consolidation with single drug bortezomib after ASCT:
is feasible
toxicity is manageable
improves degree of response
improves progression free survival
13
Conclusions II
The results support the hypothesis that a
response VGPR is important in order to
achieve a PFS prolongation
27
Nordic Myeloma Study Group
Investigators:
Iceland
Hlif Steingrímsdottir
Norway
Inger Marie Dahl
Estonia
Tobias Gedde-Dahl
Edward Laane
Iceland
Nina Guldbrandsen
Einar Haukås
Finland
R Lindås
Kari Remes
Anders Waage
Raija Silvennionen
Denmark
Niels Abildgaard
Niels Frost Andersen
Steering committee
Henrik Gregersen
Ulf-Henrik Mellqvist
Nilsaage Toffner-Clausen Peter Gimsing
Øvind Hjertner
Sweden
Stig Lenhoff
Lucia Ahlberg
Jan Westin
C Blimark
Kristina Carlsson
Karin Forsberg
Astrid Gruber
G Juliusson
Olle Linder
Hareth Nahi
A Swedin
Ingemar Turesson
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