Bortezomib, Pegylated-Lyposomal-Doxorubicin and Dexamethasone Followed by Melphalan 100 mg/m² in Elderly Newly Diagnosed Patients: An Interim Analysis.

Bortezomib has been evaluated as induction regimen to improve cyto-reduction before autologous stem cell transplant. Combinations including bortezomib, doxorubicin and dexamethasone have shown encouraging results. Melphalan at 100 mg/m² has been suggested as reduced-intensity conditioning regimen for elderly patients. In this prospective multicenter phase II study, bortezomib, pegylated-liposomal-doxorubicin and dexamethasone (PAD) followed by tandem melphalan 100 mg/m² has been investigated in newly diagnosed patients aged 65–75 years. The induction regimen included four 21-day PAD cycles (bortezomib 1.3 mg/m² days 1, 4, 8, 11, pegylated-liposomal-doxorubicin 30 mg/m² day 4 and dexamethasone 40 mg days 1–4, 8–11, and 15–18 for cycle 1 and days 1–4 for cycles 2–4). Cyclophosphamide (3 g/m²) plus G-CSF were used to harvest stem cells. Patients were then conditioned with tandem melphalan 100 mg/m² followed by stem cell infusion. A single interim analysis has been planned. Sixty-five patients have been enrolled in the study and 37 completed the induction cycles. Median age was 69 years; median β2-microglobulin 3 mg/L; median albumin 4.1 g/L; chromosome 13q deletion was detected by FISH in 35% of patients. After the 4 courses of PAD 97.1% of patients achieved at least a partial response (PR), 50% at least a very good partial response (VGPR), 11.8% an immunofixation negative complete remission (CR). After tandem melphalan 100 mg/m², all patients achieved at least a PR, 80% at least a VGPR and 30% an immunofixation negative CR. After 4 cycles of PAD, grade 3–4 hematologic events were thrombocytopenia (13.5%) and neutropenia (8.1%); more frequent grade 3–4 non-hematologic toxicities were peripheral neuropathy (21.6%) and infections (10.8%). One early toxic death was reported (central nervous system bleeding) and two patients had to discontinue therapy due to pneumonia and HBV reactivation. Eighty-two percent of patients achieved successful stem cell harvest (>4 CD34+ cells/Kg). PAD is an effective induction approach, it may improve autologous transplant results in selected elderly patients. Updated results of the interim analysis will be presented at the meeting.