Better quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma.
BACKGROUND
This retrospective pooled analysis of two phase III trials (MM-009/MM-010) compared clinical outcomes of patients who achieved a complete response or very good partial response to treatment with lenalidomide plus dexamethasone with the outcomes of those who only achieved a partial response.


METHODS
Patients (n=353) received lenalidomide (25 mg/day for 21 days of each 28-day cycle) plus dexamethasone (40 mg on days 1-4, 9-12, and 17-20 for four cycles, and only on days 1-4 after the first four cycles). Time to response, duration of response, time-to-progression, overall survival, and adverse events were investigated for patients who had a complete or very good partial response and compared with those of patients who had a partial response.


RESULTS
At the time of unblinding, 32% of patients had achieved a complete or very good partial response and 28% had a partial response. Half (50.5%) of the patients who had a partial response as their initial response achieved a complete or very good partial response with further treatment. The probability of achieving a complete or very good partial response with continued lenalidomide treatment decreased with delayed achievement of a partial response (by cycle 4 versus later); however, it remained clinically significant. With an extended follow-up of 48 months, the median response duration, time-to-progression, and overall survival were longer in patients with a complete or very good partial response than in those with a partial response (24.0 versus 8.3 months, P<0.001; 27.7 versus 12.0 months, P<0.001; not reached versus 44.2 months, P=0.021, respectively). The benefit of a complete or very good partial response was independent of when it was achieved.


CONCLUSIONS
Continuing treatment with lenalidomide plus dexamethasone to achieve best response, in the absence of disease progression and toxicity, provided deeper remissions and greater clinical benefit over time for patients in this study.
Harousseau
Jean-Luc
JL
Centre René Gauducheau, Bd. Jacques Monod, Nantes, St. Herblain, France. jl-harousseau@nantes.fnclcc.fr
Dimopoulos
Meletios A
MA
Wang
Michael
M
Corso
Alessandro
A
Chen
Christine
C
Attal
Michel
M
Spencer
Andrew
A
Yu
Zhinuan
Z
Olesnyckyj
Marta
M
Zeldis
Jerome B
JB
Knight
Robert D
RD
Weber
Donna M
DM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D017326:Clinical Trials, Phase III as Topic; D003907:Dexamethasone / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide
Leukemia. 2009 Nov;23(11):2147-52
19626046
Eur J Haematol. 2009 Nov;83(5):449-54
19519727
Clin Cancer Res. 2009 Aug 15;15(16):5250-7
19671864
J Clin Oncol. 2008 Oct 10;26(29):4777-83
18645194
Blood. 2006 Nov 15;108(10):3458-64
16840727
Br J Haematol. 2008 Oct;143(1):46-53
18673366
J Clin Oncol. 2009 Dec 1;27(34):5720-6
19826130
Blood. 2002 Nov 1;100(9):3063-7
12384400
J Clin Oncol. 2009 Dec 1;27(34):5713-9
19786667
Br J Haematol. 1998 Sep;102(5):1115-23
9753033
N Engl J Med. 1996 Jul 11;335(2):91-7
8649495
Blood. 2008 Feb 1;111(3):1101-9
17989313
Blood. 2007 Nov 15;110(10):3557-60
17690257
Mayo Clin Proc. 2007 Oct;82(10):1179-84
17908524
N Engl J Med. 2007 Nov 22;357(21):2123-32
18032762
N Engl J Med. 2007 Nov 22;357(21):2133-42
18032763
Leukemia. 2006 Sep;20(9):1467-73
16855634
Ann Hematol. 2008 Aug;87(8):623-31
18463870
Bone Marrow Transplant. 2001 May;27(10):1037-43
11438818
Blood. 2009 Oct 8;114(15):3139-46
19638622
Bone Marrow Transplant. 2006 Apr;37(8):731-7
16501593
Blood. 2009 Jul 23;114(4):772-8
19471019