Introduction Preclinical and clinical data suggest that bortezomib in combination with high-dose melphalan (Bor-HDM) provides with a synergistic effect able to improve response for MM patients undergoing auto-SCT. In the present study, patients receiving Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) induction followed by ASCT with Bor-HDM and HDM alone were evaluated.

Methods All consecutive patients treated with CyBorD induction at our center from 01/2010 to 01/2015 were evaluated. All patients received induction chemotherapy before undergoing auto-SCT. Patients received conditioning with either HDM at 200 mg/m2 (or adjusted as per renal failure) or HDM with Bortezomib (Bor-HDM). Definitions of response and progression were used according to the EBMT modified criteria. MRD negativity was assessed by flow cytometry at day-100 post-ASCT.

Results Clinical characteristics are shown in Table 1. Among 66 cases receiving CyBorD induction, 42 were conditioned with Bor-HDM and 24 with HDM. At the time of analysis, 90.5% and 91.7% of patients in the Bor-HDM and HDM group are still alive and 4 and 5 patients have already progressed, respectively. At day-100 post ASCT, ORR of 97%, with CR/VGPR rate of 81% was seen in the Bor-HDM group compared to 91% and 70% in the HDM group (p=0.2). MRD negativity was higher in the Bor-HDM group (29.2%) compared to HDM (9%) (p=0.04). Median OS and PFS was similar for Bor-HDM and HDM (p=0.8) with a median follow-up of 12 months.

In conclusion, CyBorD is an efficacious regimen for patients with MM and overall seemed to be well tolerated. Our data is one of the first to show the impact of this regimen on MRD negativity rates after receiving HDM or Bor-HDM conditioning, suggesting that higher rates of MRD negativity are seen with Bor-HDM. Further evaluation on a prospective manner and longer follow-up is required to assess the impact of Bor-HDM on OS and PFS.

Table 1.

Clinical Characteristics of patients with MM undergoing single auto-ASCT treated with CyBorD induction at our Institution

CharacteristicHDM (n=24)Bor-HDM (42)
Age (median) 55 57 
Gender
Male
Female 		19 (79.1%)
5 (20.9%) 		25 (59.5%)
17 (40.5%) 
Hb (g/L) 104 (75-157) 106 (76-139) 
Calcium (µmol/L) 2.3 (1.92-3.28) 2.3 (1.97-3.12) 
Creatinine (µmol/L) 86 (60-426) 84 (49-950) 
B2microglobulin (µmol/L) 2.73 (1.55-14.7) 3.41 (1.47-8.47) 
Albumin (g/L) 32 (21-43) 31 (16-42) 
Stage I
Stage II
Stage III 		7 (29.1%)
14 (58.3%)
3 (12.5%) 		6 (14.2%)
25 (59.5%)
11 (26.1%) 
LDH (IU/L) 172 (71-448) 192 (103-669) 
BMPC (%) 32% (5-84%) 38% (5-90%) 
Heavy chain:
IgG
IgA
IgD
Biclonal
IgM
FLC oncly 		17(70.8%)
4 (16.6%)
0
1 (4.1%)
0 (1.5%)
2 (8.3%) 		22 (52.3%)
10 (23.8%)
0
1 (2.3%)
1 (2.3%)
8 (19%) 
Light chain:
Kappa
Lambda
Biclonal 		17 (77.2%)
5 (20.8%)
1 (2%) 		21 (50%)
20 (47.6%)
1 (2.3%) 
High risk (t(4;14), t(14;16), p53 del, del 13q by CC
Standard risk 		9 (37.5%)
15 (62.5%) 		11 (26.1%)
31 (73.9%) 
CharacteristicHDM (n=24)Bor-HDM (42)
Age (median) 55 57 
Gender
Male
Female 		19 (79.1%)
5 (20.9%) 		25 (59.5%)
17 (40.5%) 
Hb (g/L) 104 (75-157) 106 (76-139) 
Calcium (µmol/L) 2.3 (1.92-3.28) 2.3 (1.97-3.12) 
Creatinine (µmol/L) 86 (60-426) 84 (49-950) 
B2microglobulin (µmol/L) 2.73 (1.55-14.7) 3.41 (1.47-8.47) 
Albumin (g/L) 32 (21-43) 31 (16-42) 
Stage I
Stage II
Stage III 		7 (29.1%)
14 (58.3%)
3 (12.5%) 		6 (14.2%)
25 (59.5%)
11 (26.1%) 
LDH (IU/L) 172 (71-448) 192 (103-669) 
BMPC (%) 32% (5-84%) 38% (5-90%) 
Heavy chain:
IgG
IgA
IgD
Biclonal
IgM
FLC oncly 		17(70.8%)
4 (16.6%)
0
1 (4.1%)
0 (1.5%)
2 (8.3%) 		22 (52.3%)
10 (23.8%)
0
1 (2.3%)
1 (2.3%)
8 (19%) 
Light chain:
Kappa
Lambda
Biclonal 		17 (77.2%)
5 (20.8%)
1 (2%) 		21 (50%)
20 (47.6%)
1 (2.3%) 
High risk (t(4;14), t(14;16), p53 del, del 13q by CC
Standard risk 		9 (37.5%)
15 (62.5%) 		11 (26.1%)
31 (73.9%) 

BMPC: Bone marrow plasma cells; FLC: Free-light chains only; CC: Conventional cytogenetics

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Disclosures

Jimenez-Zepeda:J&J: Honoraria; Amgen: Honoraria; Celgene: Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Neri:Celgene: Research Funding. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Johnson & Johnson: Research Funding; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Topics:
autologous stem cell transplant, bortezomib, conditioning (psychology), cyclophosphamide, dexamethasone, chief complaint, follow-up, free immunoglobulin light chain, albumins, antigens, cd98 light chains

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2015 by The American Society of Hematology
2015
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