Autotransplant with and without induction chemotherapy in older multiple myeloma patients: long-term outcome of a randomized trial.
Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction. For all patients, double autologous transplantation after melphalan 140 mg/m2(MEL140) was planned. The primary end point was progression-free survival. Of 420 eligible patients, 85% received a first transplant and 69% completed double transplantation. Treatment duration was short with a median of 7.7 months with induction chemotherapy cycles and 4.6 months without induction. On an intention-to-treat basis, median progression-free survival with induction chemotherapy cycles (207 patients) was 21.4 months versus 20.0 months with no induction cycles (213 patients) (hazard ratio 1.04, 95% confidence interval 0.84-1.28; P=0.36). Per protocol, progression-free survival was 23.7 months versus 23.0 months (P=0.28). Patients aged 65 years or over (55%) did not have an inferior outcome. Patients with low-risk cytogenetics [absence of del17p13, t(4;14) and 1q21 gains] showed a favorable overall survival and included the patients with sustained first remission. MEL140 was associated with a low rate of severe mucositis (10%) and treatment-related deaths (1%). Based on hazard ratio, the short treatment arm consisting of mobilization chemotherapy and tandem MEL140 achieved 96% of the progression-free survival, demonstrating its value as an independent component of therapy in older patients with multiple myeloma who are considered fit for autologous transplantation. (clinicaltrials.gov identifier: 02288741).
Schön Klinik Starnberger See, Berg, Germany cstraka@schoen-kliniken.de.|Medizinische Klinik und Poliklinik IV, Klinikum der Universität München (LMU), Germany.
Christian
C
Straka
Universitätsklinikum Ulm, Germany.
Peter
P
Liebisch
Asklepios Klinik Altona, Hamburg, Germany.
Hans
H
Salwender
Universitätsklinikum Regensburg, Germany.
Burkhard
B
Hennemann
Klinikum Oldenburg, Oldenburg, Germany.
Bernd
B
Metzner
Universitätsklinikum Tübingen, Germany.|Universitätsklinikum Würzburg, Germany.
Stefan
S
Knop
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München (LMU), Germany.
Sigrid
S
Adler-Reichel
HELIOS Klinikum Berlin-Buch, Berlin, Germany.
Christian
C
Gerecke
Klinikum Nürnberg Nord, Nürnberg, Germany.
Hannes
H
Wandt
Städtisches Klinikum Karlsruhe, Germany.
Martin
M
Bentz
Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Tim Hendrik
TH
Bruemmendorf
Städtisches Klinikum München-Harlaching, München, Germany.
Marcus
M
Hentrich
Universitätsklinikum des Saarlandes, Homburg, Germany.
Michael
M
Pfreundschuh
Universitätsklinikum Halle, Germany.
Hans-Heinrich
HH
Wolf
Universitätsklinikum Charité, Berlin, Germany.
Orhan
O
Sezer
Universitätsklinikum Würzburg, Germany.|Universitätsklinikum Charité, Berlin, Germany.
Ralf
R
Bargou
Universitätsklinikum Göttingen, Germany.
Wolfram
W
Jung
Universitätsklinikum Göttingen, Germany.
Lorenz
L
Trümper
Klinikum Bremen-Mitte, Bremen, Germany.
Bernd
B
Hertenstein
Diakonie Klinikum Stuttgart, Germany.
Else
E
Heidemann
Klinikum rechts der Isar, Technische Universität München, Germany.
Helga
H
Bernhard
Medizinische Klinik und Poliklinik III, Klinikum der Universität München (LMU), Germany.
Nicola
N
Lang
HSK Dr. Horst Schmidt Klinik, Wiesbaden, Germany.
Norbert
N
Frickhofen
Stauferklinikum Schwäbisch Gmünd, Mutlangen, Germany.
Holger
H
Hebart
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München (LMU), Germany.
Ralf
R
Schmidmaier
WISP Research Institute, Langenfeld, Germany.
Andreas
A
Sandermann
Klinikum rechts der Isar, Technische Universität München, Germany.
Tobias
T
Dechow
Universitätsklinikum Regensburg, Germany.
Albrecht
A
Reichle
Schön Klinik Starnberger See, Berg, Germany.|Medizinische Klinik und Poliklinik IV, Klinikum der Universität München (LMU), Germany.
Brigitte
B
Schnabel
Klinikum Nürnberg Nord, Nürnberg, Germany.
Kerstin
K
Schäfer-Eckart
Universitätsklinikum Ulm, Germany.
Christian
C
Langer
Universitätsklinikum Kiel, Germany.
Martin
M
Gramatzki
WISP Research Institute, Langenfeld, Germany.
Axel
A
Hinke
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München (LMU), Germany.
Bertold
B
Emmerich
Universitätsklinikum Tübingen, Germany.|Universitätsklinikum Würzburg, Germany.
Hermann
H
Einsele
D000368:Aged; D003582:Cytogenetics; D018572:Disease-Free Survival; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D008558:Melphalan
Ann Oncol. 2001 Jan;12(1):105-8
11249035
Blood. 2011 Nov 24;118(22):5752-8; quiz 5982
21849487
Bone Marrow Transplant. 2015 Feb;50(2):209-15
25387088
Br J Haematol. 2001 Sep;114(3):600-7
11552985
Lancet. 2010 Dec 18;376(9758):2075-85
21146205
Br J Haematol. 1987 May;66(1):55-62
3593657
Blood. 2004 Nov 15;104(10):3052-7
15265788
J Clin Oncol. 2012 Jun 1;30(16):1949-52
22547600
Br J Haematol. 2002 Jun;117(3):605-12
12028028
J Clin Oncol. 2012 Aug 20;30(24):2946-55
22802322
Leukemia. 2014 Feb;28(2):269-77
23974982
Blood. 1999 Jan 1;93(1):51-4
9864145
Blood. 2011 Aug 4;118(5):1239-47
21670471
Haematologica. 2016 Sep;101(9):1110-9
27479825
Bone Marrow Transplant. 1998 May;21(10):1037-41
9632278
N Engl J Med. 2012 May 10;366(19):1770-81
22571201
Am J Hematol. 2008 Aug;83(8):614-7
18429054
N Engl J Med. 2003 May 8;348(19):1875-83
12736280
Clin Lymphoma Myeloma Leuk. 2013 Oct;13(5):541-51
23810244
N Engl J Med. 2012 May 10;366(19):1759-69
22571200
Oncology. 2003;65 Suppl 2:94-8
14586157
Blood. 2010 Aug 5;116(5):679-86
20385792
Haematologica. 2015 Oct;100(10):1340-9
26160877
Blood. 1999 Jan 1;93(1):55-65
9864146
Bone Marrow Transplant. 2007 May;39(10):605-11
17369867
Hematol Oncol Stem Cell Ther. 2011;4(1):30-6
21460604
Blood. 2012 Aug 23;120(8):1589-96
22791289
Ann Oncol. 2014 Jan;25(1):189-95
24356629
Lancet. 2007 Oct 6;370(9594):1209-18
17920916
N Engl J Med. 2014 Sep 4;371(10):895-905
25184862
Leuk Lymphoma. 2012 Jan;53(1):118-22
21780997
N Engl J Med. 2014 Sep 4;371(10):906-17
25184863
Biol Blood Marrow Transplant. 2014 Nov;20(11):1796-803
25046833
N Engl J Med. 2008 Aug 28;359(9):906-17
18753647
N Engl J Med. 1996 Jul 11;335(2):91-7
8649495
Blood. 2013 Aug 22;122(8):1376-83
23775712
N Engl J Med. 1984 May 24;310(21):1353-6
6546971
Blood. 2002 Feb 1;99(3):731-5
11806971
Br J Haematol. 1998 Sep;102(5):1115-23
9753033
J Clin Oncol. 2010 Oct 20;28(30):4621-9
20823406
Leukemia. 2014 May;28(5):1122-8
24157580
N Engl J Med. 2012 May 10;366(19):1782-91
22571202