Bortezomib in Multiple Myeloma: Treatment and Retreatment. A Single Center Experience.

Introduction: Although major advances have been done in the treatment of multiple myeloma (MM) patients (pts), it still remains incurable with conventional or high dose chemotherapy with autologous stem cell rescue (ASCT). A novel agent which takes standard place in the management of MM pts is bortezomib.

Patients and methods: The aim of our study is to evaluate prospectively the response to bortezomib (1.3mg/m2 on days 1, 4, 8, 11 in a 21-day cycle for up to 8 cycles) in MM pts relapsed or refractory after standard therapy. We evaluate its re-administration (with the same schedule) in a number of pts who have relapsed after a complete course of bortezomib as well. We also present the pts who have received bortezomib as maintenance therapy (1.3mg/m2 on days 1 and 4 in a 28-day cycle).

Results: From September 2004 until August 2007 36 MM pts have been included. The characteristics of the pts are as follows: 21 males, 15 females, median age at diagnosis 57 years (41–70). Eleven pts was IgGκ, 8 pts IgGλ, 8 IgAκ,3 IgAλ, 3 κ light chain and 3 λ light chain. According to the Durie-Salmon staging system 3 pts was IA, 13 IIA, 16 IIIA and 4 IIIB. The median number of prior therapies was 3 (1–7). Nineteen pts had received ASCT prior to bortezomib. Median time from diagnosis to the first dose of bortezomib was 47 months (5–156). Twenty eight pts received bortezomib for relapse and 8 for refractory disease. Median follow-up time since bortezomib administration was 12 months (1–30). The pts who achieved CR, VGPR or was in PD for two successive cycles discontinued treatment. The median number of cycles received was 5.5 (1–8). The response outcome, according to the International Myeloma Working Group response criteria, for the pts who received up to 4 cycles, was: 7 pts in CR, 5 pts in VGPR, 7 pts in PR, 7 pts in SD, 6 pts in PD, 3 pts died due to PD and 1 due to pulmonary complications. The response outcome for the pts who received up to 8 cycles was: 5 pts in CR, 4 pts in VGPR, 5 pts in PR, 4 pts in SD, 3 pts in PD. The median time to progression for responders was 8 months (1–26). The overall outcome was CR 22.3%, VGPR 16.7%, PR 11.1%, SD 19.4% and PD 30.5%. Ten pts who achieved CR, VGPR or PR continued maintenance therapy with bortezomib. The median time of maintenance therapy until relapse was 7 months (2–16). Six pts from the maintenance group who relapsed re-treated with bortezomib. Also 1 patient who relapsed without receiving bortezomib maintenance re-treated as well. After a median number of 6 cycles (1–8) of re-treatment, 1 patient is in VGPR, 1 in PR, 3 in SD and 2 in PD.

Conclusions: We conclude that bortezomib offers an overall response rate of 50.1% (CR, VGPR, PR) in heavily pre-treated MM pts achieved even from the very first cycle. Probably the addition of bortezomib as maintenance therapy may prolong the time to progression in responding pts. Retreatment is also an attractive option, but we cannot extract safe conclusions due to our limited sample size.