Background:166Holmium-DOTMP is a beta emitting radiophosphonate that localizes specifically to the bone surfaces and can deliver high dose radiation both to the bone and bone marrow. Phase I/II trials have shown feasibility and tolerability when combined with a standard conditioning regimen of melphalan with or without total-body irradiation (TBI) in pts with multiple myeloma (MM) undergoing autologous stem cell transplantation (SCT).

Purpose: To define the potential impact of 166Holmium-DOTMP (HO) in combination with melphalan when compared to a standard conditioning regimen of melphalan 200 mg/m2 (M200) in MM patients undergoing auto SCT.

Methods: We performed a retrospective review of transplant outcomes among patients with MM who received an auto SCT between 1/98-12/01 with either M200 or a melphalan-HO combination and were in a 1ry refractory or 1st remission consolidation state. Univariate analysis was performed for response, survival and event free survival.

Results: 104 pts were identified. Patient characteristics are summarized in Table 1. In brief the HO group had a higher percentage of patients with IgA disease, otherwise there were no siginificant differences in prognostic factors among the groups. Transplant outcomes are summarized in Table 2. The HO group had a trend towards a higher conversion to CR rate (51% vs 32%) for all patients, (23% vs 12.5%) for 1ry refractory patients and similar OS rates and a higher NRM rate of 12% vs 3% when compared to MEL200. When the analysis was limited to patients receiving <2400 mCi the HO group had a trend towards longer PFS (33 months vs 24 months) with no difference in NRM rates. The OS rate at 5 yrs was 54% for the HO group vs 43% for the MEL200 group, among the 21 patients in the HO group receiving <2400 mCi the 5 yr OS was 61% (Figure 1).

Conclusion: 166Holmium-DOTMP in combination with high dose melphalan can result in higher CR rates than melphalan 200 mg/m2 alone, when given in optimal doses (<2400 mCi) the results seem to be superior and the toxicities are minimal. Targeted skeletal radiotherapy with 166Holmium-DOTMP in combination with melphalan 200 mg/m2 is safe and effective and should be further studied in Phase III trials in all patients with MM undergoing autologous SCT, based on these data other methods of targeted skeletal radiotherapy should also be pursued.

Patient Characteristics

HO <2400 mCiHO ≥ 2400 mCiMelphalan 200p MEL200 vs HO
N 21 20 63  
Median Age 52 (45–61) 53 (36–64) 55 (35–69) NS 
IgA Type 33% 40% 14% .03 
Median B2M @ Dx 3.15 3.15 3.5 NS 
Durie Salmon III 43% 55% 67% NS 
Number with Δ13 0 0 3 NS 
CR/PR @ SCT 5%/57% 5%/70% 6%/68% NS 
1ry Refractory 38% 25% 25% NS 
HO <2400 mCiHO ≥ 2400 mCiMelphalan 200p MEL200 vs HO
N 21 20 63  
Median Age 52 (45–61) 53 (36–64) 55 (35–69) NS 
IgA Type 33% 40% 14% .03 
Median B2M @ Dx 3.15 3.15 3.5 NS 
Durie Salmon III 43% 55% 67% NS 
Number with Δ13 0 0 3 NS 
CR/PR @ SCT 5%/57% 5%/70% 6%/68% NS 
1ry Refractory 38% 25% 25% NS 
View Large

Transplant Outcomes

HO <2400 mCiHO ≥ 2400 mCiMEL200MEL 200 vs HO
ORR/CR conversion 95%/55% 90%/48% 92%/32% NS/.06 
NRM 5% 20% 3% .07 
Median OS NR 31 months 52 months NS 
Median EFS 30 months 23 months 19 months .3 
HO <2400 mCiHO ≥ 2400 mCiMEL200MEL 200 vs HO
ORR/CR conversion 95%/55% 90%/48% 92%/32% NS/.06 
NRM 5% 20% 3% .07 
Median OS NR 31 months 52 months NS 
Median EFS 30 months 23 months 19 months .3 
View Large

Topics:
holmium, transplantation, melphalan, brachial plexus neuritis, immunoglobulin a, radiation therapy, autologous stem cell transplant, disease remission, multiple myeloma, prognostic factors

Author notes

Corresponding author

2005, The American Society of Hematology
2005
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