Abstract 824

There is no standard therapy for MM relapsing after autologous hematopoietic cell transplantation (AHCT). A second AHCT can result in additional progression-free survival (PFS). Nonmyeloablative/reduced intensity conditioning (NST/RIC) allogeneic transplantation (AlloHCT) has the advantages of a tumor-free graft and the potential of a graft-versus-myeloma (GVM) effect. Few studies have compared second AHCT vs. NST/RIC AlloHCT.

We compared the outcome of second AHCT or NST/RIC AlloHCTafter relapse from prior AHCT in patients with MM reported to the CIBMTR from 1995–2008. Recipients of planned tandem transplants, AlloHCT for graft failure or second malignancies and myeloablative alloHCT were excluded. 137 patients underwent second AHCT and 152 underwent NST/RIC AlloHCT (32 HLA-identical sibling and 120 unrelated donor). The table below illustrates clinical characteristics and patient outcomes. AlloHCT recipients were significantly younger (median 53 years [yrs] of age vs. 56 yrs in the AHCT cohort (p < 0.001). The groups were similar in Karnofsky performance score (KPS) and gender. Conditioning regimens differed between groups. In the AHCT cohort, 85% were melphalan based. In the NST/RIC alloHCT cohort, 38% received melphalan + other drugs and 24% received total body irradiation +/− other drugs but no melphalan (p <0.001). Time from 1st to 2nd transplant was significantly shorter for the AlloHCT cohort (30 vs. 23 months, p = 0.014). Acute graft-versus-host disease (GVH) was 35% at 60 days while chronic GVHD was 44% at 36 months.

Patient CharacteristicsAutologousAllogeneicP-value
Number of patients 137 152  
Age at 2nd transplant, median (range), years 56 (28–65) 53 (32–65) 0.001* 
Gender    
    Male 84 (61) 90 (59) 0.720 
Karnofsky Score pre-transplant    
    ≥90% 68 (50) 76 (50) 0.884 
Time from 1st to 2nd transplant, months, median (range) 30 (6–122) 23 (6–78) 0.014* 
    6–24 months 44 (32) 78 (51) 0.001* 
    >24 months 93 (68) 74 (49)  
Outcomes    
Treatment-related Mortality (TRM)    
12 months 2 (1–5) 13 (8–19) <0.001* 
60 months 4 (2–8) 15 (10–21) <0.001* 
Relapse/Progression    
12 months 51 (43–58) 72 (64–79) <0.001* 
36 months 82 (76–88) 80 (73–86) 0.655 
Progression-free survival    
12 months 47 (40–54) 15 (10–21) <0.001* 
36 months 13 (9–19) 6 (3–10) 0.038* 
Overall Survival (OS)    
12 months 83 (77–89) 51 (42–58) <0.001* 
36 months 46 (37–54) 20 (14–27) <0.001* 
60 months 29 (21–38) 9 (5–15) <0.001* 
Patient CharacteristicsAutologousAllogeneicP-value
Number of patients 137 152  
Age at 2nd transplant, median (range), years 56 (28–65) 53 (32–65) 0.001* 
Gender    
    Male 84 (61) 90 (59) 0.720 
Karnofsky Score pre-transplant    
    ≥90% 68 (50) 76 (50) 0.884 
Time from 1st to 2nd transplant, months, median (range) 30 (6–122) 23 (6–78) 0.014* 
    6–24 months 44 (32) 78 (51) 0.001* 
    >24 months 93 (68) 74 (49)  
Outcomes    
Treatment-related Mortality (TRM)    
12 months 2 (1–5) 13 (8–19) <0.001* 
60 months 4 (2–8) 15 (10–21) <0.001* 
Relapse/Progression    
12 months 51 (43–58) 72 (64–79) <0.001* 
36 months 82 (76–88) 80 (73–86) 0.655 
Progression-free survival    
12 months 47 (40–54) 15 (10–21) <0.001* 
36 months 13 (9–19) 6 (3–10) 0.038* 
Overall Survival (OS)    
12 months 83 (77–89) 51 (42–58) <0.001* 
36 months 46 (37–54) 20 (14–27) <0.001* 
60 months 29 (21–38) 9 (5–15) <0.001* 
*

Significant difference

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The most common cause of death in both cohorts was progression of MM. On multivariate analysis risk of death was higher for alloHCT (HR 2.38, p < 0.001), KPS < 90 (HR 1.96, p < 0.001), and year of transplant (2004 or earlier, HR 1.77, p = < 0.001). AlloHCT was associated with significantly higher risk of TRM (HR 7.14, p < 0.001). Durie-Salmon Stage III was associated with a higher risk of relapse (HR 2.70, 95% CI: 1.93–3.80, P<0.001) and treatment failure in the alloHCT group (HR 3.05, 95% CI: 2.20–4.22, p < 0.001).

We conclude that patients with MM who underwent NST/RIC alloHCT after AHCT failure experienced higher TRM and lower probability of survival compared with those who received second AHCT. Because genetic risk data were not available for these patients, we cannot exclude the possibility that the alloHCT population was a higher risk population. Despite this limitation, our data demonstrate that the value of alloHCT after relapse from prior AHCT is limited.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
antepartum fetal nonstress test, multiple myeloma, transplantation, homologous, transplantation, melphalan, tissue transplants, graft-versus-host disease, acute, graft-versus-host disease, chronic, hematopoietic stem cell transplantation, human leukocyte antigens

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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