Total Body Irradiation (TBI) or Busulfan (Bu) Plus High Dose Melphalan After Bortezomib (Bz) Containing Regimen As Front Line Treatment of High Risk Multiple Myeloma (MM) Patients with 17p Deletion and/or t(4;14) Translocation

Abstract 4501

Despite recent improvement of overall survival of MM due to the use of novel agents, the high risk sub group of patients, especially with 17p deletion and/or t(4;14) still have a poor prognosis. New therapeutic strategies are needed to improve this outcome. We report preliminary results of a study using TBI or intravenous Bu to reinforce the high dose Melphalan after a Bz containing regimen as induction therapy in patients with 17p- and/or t(4;14) MM.

Between 01/2009 and 08/2010, twenty three patients (7F and 16M, median age 55 years) were treated. At diagnosis, anemia and hypercalcemia and renal failure were noted in 14, 8 and 4 patients, respectively. The median percentage of bone marrow plasma cell was 30% and 10 (43%) had an IgA isotype. One patient had a light chain MM (65g/dl), a plasma cell leukemia was diagnosed in one patient and one patient presented with specific fever and biological inflammatory features. A 17p deletion and t(4;14) translocation were detected, using RQ-PCR and FISH analysis, in 7 and 17 patients, respectively with one patient harboring the two abnormalities. Patients were treated with a median of 3 cycles of the VTD (Bz/Thalidomide/dexamethasone) combination, 12 received a PAD regimen (Bz/doxorubicine/dexamethasone) and 1 had 4 cycles of VD (Bz/ dexamethasone). High dose therapy consisted in Melphalan 140 mg/m2 associated with Bu in 16 patients and TBI in 7 patients. Thirteen patients (4 with 17p- and 9 with t(4;14) had a consolidation with 4 cycles of VTD (n=11) or TD (n=2).

Grade >2 mucositis and gastrointestinal toxicity was noted in all patients treated with TBI but Bu was well tolerated. No patient died early from toxicity. One patient had a reactivation of a virus B hepatitis and one patient had a peripheral thrombocytopenia 3 months after HDT. No venous occlusion disease was observed. Overall response rate after high dose therapy (HDT) was 91% (21/23) including 9 VGPR, 6 CR+nCR and 6 PR. Consolidation treatment led to an improvement of response in 4 patients. Nine patients relapsed, including 6 within 6 months after HDT and 3 at 8,9, and 10 months, respectively. At analysis, five patients had died, all because of progressive disease, and 14 patients (10 CR and 4 VGPR) patients were still in first remission.

Although a larger number of patients and additional follow up are needed, these data suggest that intensifying high dose therapy regimen is feasible and correctly tolerated in pts with high risk MM, especially using intravenous Busulfan, and may be an interesting approach to improve the current poor prognosis of patients with 17p deletion and/or t(4;14).