Abstract
Abstract 4464
Standard therapy for multiple myeloma (MM) includes initial autologous hematopoietic cell transplantation (autoHCT1) but this is not curative and most patients will relapse. Data on salvage autoHCT2 or allogeneic HCT (alloHCT2) are limited and the optimal salvage strategy is unknown.
Retrospective review of MM patients over 18 years of age who relapsed after autoHCT1 and underwent salvage autoHCT2 or alloHCT2 between 1995–2011 at our institution. Tandem auto-autoHCT or auto-alloHCT were excluded. Disease response was defined by the International Myeloma Working Group criteria and assessed 100 days after HCT2.
Patient characteristics of autoHCT2 (N=27) and alloHCT2 (N=19) (Table 1) were not significantly different except the alloHCT2 median age was significantly lower (54 years) than for autoHCT2 (62 years) and more alloHCT2 patients had KPS 70% or more. Median followup of both groups was 57 months. Complete and very good partial remission (CR/VGPR) improved from 7% to 56% after autoHCT2 and from 26% to 37% after alloHCT2. Of 15 patients with progressive disease (PD) who had autoHCT2, 5 achieved CR/VGPR with 7 PR. Nonrelapse mortality (NRM) at 1 year was 3.7% for autoHCT2 and 5.3% for alloHCT2 (p=.901). Median progression free survival (PFS) and overall survival (OS) for autoHCT2 (19 months, 23 months) and alloHCT2 (6 months, 19 months) were not significantly different (p=0.156 and p=0.255). On multivariate analysis, time from autoHCT1 to relapse less than 1year vs. 1year or more (HR 24.81 [95% CI 2.4–249.9]) and no maintenance therapy vs. given after autoHCT2 (HR 12.19 [95% CI 2.5–249.9] impacted OS after autoHCT2. On multivariate analysis, only time from autoHCT1 to relapse less than 1 year vs. 1 year or more (HR 18.55 [95% CI 2.28–150.57]) impacted PFS after autoHCT2. For alloHCT2, no factors impacted NRM, PFS or OS including chemosensitivity, acute/chronic GVHD, donor lymphocyte infusion, antithymocyte globulin, reduced intensity vs. myeloablative conditioning, matched sibling or unrelated donor, time from autoHCT1 to relapse less than 1 year vs. 1 year or more. For those with relapse from autoHCT1 less than 1 year vs. 1 year or more undergoing autoHCT2, median OS was 15 months (0–53) vs. not yet reached (p=0.003) and median PFS was 5 months (0–49) vs. not yet reached. (p=0.002) Major causes of death for alloHCT2 were PD (n= 5), GVHD (n=3), while for autoHCT2, PD (n=10), infection (n=3).
Salvage autoHCT2 and alloHCT2 are both feasible for patients with post autoHCT1 MM relapse. Relpase 1 year or more from autoHCT1 predicts for better PFS and OS in the autoHCT2 group. Those with progressive disease can also be salvaged by autoHCT2. Maintenance therapy after autoHCT2 is beneficial and should routinely be used.
. | autoHCT2 N=27 . | alloHCT2 N=19 . |
---|---|---|
M/F | 16/11 | 10/9 |
Median age yr (range)* | 62 (32–69)* | 54 (43–63)* |
Median months (mo.): diagnosis to autoHCT1 | 8 (3–39) | 8 (5–30) |
KPS at HCT2 ** 70% or more vs. less than 70% | 20/7** | 19/0** |
HCT comorbidity index | ||
0,1 | 5 | 8 |
2,3 | 10 | 7 |
>3 | 12 | 4 |
Durie-Salmon: I/II/III/unknown | 4/6/17 | 0/5/13/1 |
ISS stage: I/II/III/unknown | 11/4/5/7 | 9/5/3/2 |
Cytogenetics | ||
High/intermediate risk | 9 | 4 |
Standard risk | 15 | 13 |
Unknown | 3 | 2 |
IgG | 12 | 10 |
IgA | 7 | 8 |
Light chain | 8 | 0 |
nonsecretory | 1 | |
Lines of chemo pre HCT2 | 1 (1-5) | 2 (1-5) |
Chemosensitive pre HCT2:Y/N | 11/16 | 11/8 |
Induction pre HCT2:Conventional/novel agents | 6/21 | 12/7 |
Time from autoHCT1 to relapse: mo.(range) | 16.5 (4-42) | 12 (2-45) |
Time from autoHCT1 to relapse: less than 1yr vs.1yr or more | 12/15 | 9/10 |
Time from autoHCT1 to HCT2: mo. (range) | 30 (5–104) | 21 (7–91) |
Conditioning at autoHCT1:BuCy/melphalan | 9/18 | 13/6 |
Conditioning at alloHCT2: Reduced intensity[FLUMEL)/Myeloablative [BUCY] | 16/3 | |
Conditioning for autoHCT2:BuCy/melphalan | 11/16 | |
Donor | ||
Matched sibling related 6/6 | 13 | |
Matched unrelated 10/10 | 5 | |
Haploidentical related | 1 | |
Stem cell type: BM/PB | 0/27 | 1/18 |
1995-2005 | 6 | 8 |
2006-2011 | 21 | 11 |
Disease status pre/post HCT2 | ||
CR | 0/4 | 2/3 |
VGPR | 2/11 | 3/4 |
PR | 9/7 | 6/4 |
SD | 1/2 | 8/0 |
PD | 15/3 | 0/8 |
Maintenance post HCT2: Y/N | 12/15 | 3/16 |
Median mo. of f/u from diagnosis(range) | 57 (19–115) | 57 (22–154) |
. | autoHCT2 N=27 . | alloHCT2 N=19 . |
---|---|---|
M/F | 16/11 | 10/9 |
Median age yr (range)* | 62 (32–69)* | 54 (43–63)* |
Median months (mo.): diagnosis to autoHCT1 | 8 (3–39) | 8 (5–30) |
KPS at HCT2 ** 70% or more vs. less than 70% | 20/7** | 19/0** |
HCT comorbidity index | ||
0,1 | 5 | 8 |
2,3 | 10 | 7 |
>3 | 12 | 4 |
Durie-Salmon: I/II/III/unknown | 4/6/17 | 0/5/13/1 |
ISS stage: I/II/III/unknown | 11/4/5/7 | 9/5/3/2 |
Cytogenetics | ||
High/intermediate risk | 9 | 4 |
Standard risk | 15 | 13 |
Unknown | 3 | 2 |
IgG | 12 | 10 |
IgA | 7 | 8 |
Light chain | 8 | 0 |
nonsecretory | 1 | |
Lines of chemo pre HCT2 | 1 (1-5) | 2 (1-5) |
Chemosensitive pre HCT2:Y/N | 11/16 | 11/8 |
Induction pre HCT2:Conventional/novel agents | 6/21 | 12/7 |
Time from autoHCT1 to relapse: mo.(range) | 16.5 (4-42) | 12 (2-45) |
Time from autoHCT1 to relapse: less than 1yr vs.1yr or more | 12/15 | 9/10 |
Time from autoHCT1 to HCT2: mo. (range) | 30 (5–104) | 21 (7–91) |
Conditioning at autoHCT1:BuCy/melphalan | 9/18 | 13/6 |
Conditioning at alloHCT2: Reduced intensity[FLUMEL)/Myeloablative [BUCY] | 16/3 | |
Conditioning for autoHCT2:BuCy/melphalan | 11/16 | |
Donor | ||
Matched sibling related 6/6 | 13 | |
Matched unrelated 10/10 | 5 | |
Haploidentical related | 1 | |
Stem cell type: BM/PB | 0/27 | 1/18 |
1995-2005 | 6 | 8 |
2006-2011 | 21 | 11 |
Disease status pre/post HCT2 | ||
CR | 0/4 | 2/3 |
VGPR | 2/11 | 3/4 |
PR | 9/7 | 6/4 |
SD | 1/2 | 8/0 |
PD | 15/3 | 0/8 |
Maintenance post HCT2: Y/N | 12/15 | 3/16 |
Median mo. of f/u from diagnosis(range) | 57 (19–115) | 57 (22–154) |
statistically significant p=.002.
statistically significant p=.031.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.