Bortezomib, Doxorubicin and Dexamethasone (PAD) Combination Therapy Followed by Thalidomide and Dexamethasone (TD) as a Salvage Treatment for Relapsed Multiple Myeloma (MM): Preliminary Analysis of Efficacy and Safety.

Introduction: PAD was reported to be highly effective regimen as an induction therapy before high dose therapy. TD is an another effective regimen with no cross resistance. We conducted a phase II study with PAD followed by TD in relapsed MM to test effectiveness of this combination.

Method: Patients were planned to receive 6 cycles of PAD, (bortezomib 1.3 mg/m² days 1, 4, 8 and 11, doxorubicin 4.5 mg/m² days 1–4, dexamethasone 40 mg days 1–4, every 21 days). Responders following 6 cylces of PAD received 12 cycles of TD (thalidomide 100 mg days 1–28 and dexamethasone 40 mg days 1–4, every 28 days). In patients with progression during PAD therapy, regimen was changed to 12 cycles of thalidomide 200 mg days 1–28 and dexamethasone 40 mg days 1–4, every 28 days.

Result: This study aimed to enroll 40 patients till Oct 2007 and we are reporting preliminary result with 35 patients. Efficacy could be assessed in 29 patients. After two cycles of PAD, 29 patients showed response with 5 CR. Overall response rate to 6 cylces of PAD was 96.4% with 39.3% CR. Six of total 13 patients with TD showed further improvement of response status with 5 additional CR. Overall response to PAD followed by TD was 92.8%: CR 57.1%, nCR 10.7%, VGPR 7.1%, PR 17.9%, SD 3.6%, PD 3.6%. There was no prognostic factor for CR+nCR achieving in the univariate analysis. The median follow-up was 8.4 months with 1 year PFS 66.8% and 1 year OS 59.4%. One hundred fourty-six PAD cycles (median 5, range 1–6) in 35 patients were assessable for safety. The most common hematologic toxicity was thrombocytopenia, with grade 3/4 in 37.1%. Grade 3/4 neutropenia was observed in 5.8%. Sensory neuropathy occurred with grade 2 in 31.4% and grade 3 in 8.6%. The median dose intensity was 1.44 mg/m²/week for bortezomib and 5.25 mg/m²/week for doxorubicin, which correspond 83.2% and 87.5% of the planned dose intensities, respectively. A total of 112 TD treatment cycles (median 0, range 0–12 cycles) was administered. Two patients developed grade 3 neutropenia. One patient die by the pneumonia.

Conclusion: PAD followed by TD in patients with relapsed multiple myeloma is very active and tolerable. Updated results will be presented at the meeting.

*Protocol Number: KMM55-NCT00319865