ORIGINAL ARTICLE
Salvage treatment with upfront melphalan 100 mg/m
2
and consolidation with novel drugs for fulminant
progression of multiple myeloma
Marta Krejci
&
Zdenek Adam
&
Tomas Buchler
&
Andrea Krivanova
&
Ludek Pour
&
Lenka Zahradova
&
Michal Holanek
&
Viera Sandecka
&
Jiri Mayer
&
Jiri Vorlicek
&
Roman Hajek
Received: 16 March 2009 / Accepted: 29 October 2009 /Published online: 19 November 2009
#
Springer-Verlag 2009
Abstract Patients (pts) with fulminant progression (FPG) of
multiple myeloma (MM) after autologous stem cell trans-
plantation (ASCT) have poor prognosis. Pancytopenia,
extramedullary disease, and/or renal impairment are often
present, and treatment options are limited. We have retro-
spectively evaluated 31 pts with FPG of MM after ASCT
who were treated upfront salvage therapy with melphalan
100 mg/m
2
(MEL 100) followed by PBSC support and
consolidation therapy using regimens containing thalidomide
(n=16) or bortezomib (n=15). The overall response rate
(ORR) was 58% (18/31). After MEL 100, one patient achieved
complete remission (3%), 26% of pts very good partial
remission, 29% of pts partial remission, and 42% of pts stable
disease. Progression within 3 months after MEL 100 occurred
in 35% of pts. The median follow-up from MEL 100 was
8 months. The median TTP was 5 months (range, 2–
15 months), and the median OS was 8 months (range, 3–
23 months). There were no treatment-related deaths. In ful-
minant progression of MM, upfront MEL 100 is a safe salvage
regimen with good response rate (ORR, 58%). Treatment with
upfront MEL 100 followed by a thalidomide- or bortezomib-
based regimen can prolong overall survival to more than
12 months in 33% of pts with fulminant progression of MM.
Keywords Multiple myeloma
.
Fulminant progression
.
Melphalan
.
Novel drugs
Introduction
The introduction of new drugs in the last decade has
resulted in a significant progress in the treatment of
multiple myeloma (MM) [1]. Combinations of novel agents
with conventional therapies have prolonged progression-
free survival and increased response rates by overcoming
drug resistance [2–4].
Patients with rapid fulminant progression (FPG) of MM
after autologous stem cell transplantation (ASCT) have
poor prognosis. Treatment options are limited, and
myeloma-related pancytopenia, extramedullary disease,
and/or renal impairment are often present.
Encouraging results have been reported for the
treatment with the combination of melphalan 100 mg/m
2
,
bortezomib, thalidomide, and dexamethasone with stem
cell support. The overall response rate (ORR) was as
high as 65% in patients with refractory or relapsed
myeloma [5]. Salvage treatment with upfront melphalan
100 mg/m
2
(MEL 100) followed by autologous periph-
eral blood stem cell (PBSC) support can stop the
progression of MM almost immediately [6]. This strategy
provides an opportunity for the application of consolida-
tion treatment with novel drugs, such as thalidomide or
bortezomib.
The aim of our retrospective analysis was to
evaluate the efficacy and toxicity of upfront MEL 100
with PBSC support and subsequent consolidation with
the combination of chemotherapy and novel drugs
including thalidomide or bortezomib for FPG of MM
after ASCT.
M. Krejci (*)
:
Z. Adam
:
A. Krivanova
:
L. Pour
:
L. Zahradova
:
M. Holanek
:
V. Sandecka
:
J. Mayer
:
J. Vorlicek
:
R. Hajek
Department of Internal Medicine–Hematooncology,
Masaryk University Hospital,
Jihlavska 20,
Brno 625 00, Czech Republic
e-mail: mkrejci@fnbrno.cz
T. Buchler
1st Faculty of Medicine, Department of Oncology,
Thomayer University Hospital,
Prague, Czech Republic
Ann Hematol (2010) 89:483–487
DOI 10.1007/s00277-009-0862-z