Response to Bortezomib in Combination after Relapse o Non-Response to First Treatment with Bortezomib Alone in Myeloma Multiple Patients.

Background: Bortezomib has been shown to be effective in multiple myeloma (MM), but there is a limited experience in response to re-treatment.

Aims: To evaluate the efficacy of Bortezomib in refractory/relapsed MM.

Patients and methods: 41 patients treated with Bortezomib (1,3 mg/m2 on days 1,4,8,11 in a 21-day cycle) in second or more line as clinical practice protocol were included. The response was evaluated according EGBMT criteria (Bladé J, Samson D, Reece E et al). Patients that no have reached response after 4 courses or relapsed after CR or PR received a combination of: bortezomib+dexamethasone (group BD) or bortezomib+melphalan+prednisone (group BMP). Adverse effects were registered.

Results: 39 valuable patients (males 43.0%). Mean age 59.9 years (34–82), over 65 years (66.6%). Bortezomib was administered in second line: 10 (25.6%), in third or more: 29 (74.3%). Overall Response: 76.4%: (CR+PR 70.5%, MR 5.9%), (CR 41.1%/CR-IFE negative 14.7%), Mean courses to reached response: 4.7. No relation to response and presence or not chromosomal aberrations. At 32 months on follow-up 9 patients had dead (26.4%) and 15 (44.1%) maintained response without therapy. In 17 patients (43.5%), a combination of BD (10 patients) or BMP (7 patients) were administrated by relapse or progression. Responses: group BD 6 PR, 3 NR; 1NV group BM P 3 PR, 3 NR, 1NV. Adverse events: thrombocytopenia 38.4 (grade III: 17.9), fatigue 38.5%, peripheral neuropathy 33.3, constipation 35.8%, diarrhea 20.5%, ZHV 12.8%, infection 33.3, pyrexia 10.2%, hypotension 5.1%, grade 3 leucopenia 12.8%. In 3 patients (7.6%) the therapy was disrupted by toxicity. We haven’t found any differences in adverse events in patients treated with bortezomib in combination.

Conclusions: Related to the synergism of Bortezomib in combination, the re-treatment induces response (60%) in refractory MM without severe adverse effects. In spite of the scarce follow-up some patients could be benefit in re-treatment with Bortezomib. It is necessary to explore more combinations and to know the results of clinical trials. When there is not response after the 4^th course of Bortezomib it is recommendable to use in combination