Abstract
Del(13) is a powerful adverse prognostic factor in patients with myeloma. A small subset analysis from a randomized multi-center study comparing dexamethasone to bortezomib for relapsed myeloma suggested that the outcome of bortezomib-treated patients was not affected by del(13) (Jagannath et al, ASCO 2005). We studied patients with relapsed myeloma treated with bortezomib on whom complete karyotype data were available to determine the effect of del(13) on response rates and survival. To ensure consistency, this analysis was confined to 47 patients (44–85 y; median 62) who received all their therapy at Northwestern and in whom all cytogenetic analyses were performed in a single laboratory. 40 had failed prior thalidomide and 32 had failed prior high-dose therapy. All patients were treated with bortezomib as a single agent in the standard fashion initially. Dexamethasone ± thalidomide were added if there was no response. Progression after initial response or lack of response to bortezomib ± thalidomide ± dexamethasone was classified as treatment failure. Overall response rate (≥50% decline in paraprotien) was 72%. Complete clearance of paraprotein was seen in 32%. The median event-free (EFS) and overall (OS) survival durations from the start of therapy were 227 and 777 days. OS was higher in responders (777 vs 373 days; P=0.015) as was EFS (259 vs 120 days; P=0.0001). As the table shows, del(13) did not affect response rates.
Response to bortezomib by del(13) status (P=0.69)
| Paraprotein response | Del(13) (n=13) | No del(13) (n=34) |
|---|---|---|
| Any response vs no response; P=0.31 | ||
| No response | 5 (38%) | 8 (24%) |
| 50–94% decline | 3 (23%) | 10 (29%) |
| 95–99% decline | 2 (15%) | 4 (12%) |
| 100% decline | 3 (23%) | 12 (35%) |
| Paraprotein response | Del(13) (n=13) | No del(13) (n=34) |
|---|---|---|
| Any response vs no response; P=0.31 | ||
| No response | 5 (38%) | 8 (24%) |
| 50–94% decline | 3 (23%) | 10 (29%) |
| 95–99% decline | 2 (15%) | 4 (12%) |
| 100% decline | 3 (23%) | 12 (35%) |
No variable influenced response significantly in Cox analysis. However, there was a trend (P=0.07) towards lower response rates in patients relapsing after prior transplant. When PCLI (available in 34 patients) was included in the model, there was a trend (P=0.08) towards lower likelihood of 100% responses with del(13). Response to bortezomib and age ≤ 60 were associated with significantly better EFS with/without PCLI in the model. PCLI ≥1% was the only factor associated with poorer OS when included in the model. When PCLI was excluded, response to bortezomib was associated with significantly superior OS.
Figure
While OS and EFS did not seem to be influenced by del(13), the curves shown below suggest that differences may become apparent with longer follow-up in a larger number of patients.
Figure
Thus, small patient numbers in this study and that of Jagannath et al, and a trend towards a lower likelihood of complete paraprotein clearance with del(13) in our experience suggests that more data are needed before any definitive conclusions can be drawn on the impact of del(13) on bortezomib therapy.
