Abstract

Abstract 2309

Poster Board II-286

Background

There is a role for novel preparative regimens in multiple myeloma to improve the outcome after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto HCT). Bortezomib is an active agent in newly diagnosed or relapsed multiple myeloma, and has synergistic activity with melphalan. We conducted a randomized phase II trial to determine the safety and efficacy of adding bortezomib to a preparative regimen of arsenic trioxide (ATO), ascorbic acid (AA) and melphalan.

Methods

auto HCT, with preparative regimen melphalan 100 mg/m2 IV on days -4 and -3, AA 1000 mg/day IV on days -9 to -3 and ATO 0.25 mg/kg IV on days -9 to -3. Patients were randomized to 3 arms; no bortezomib (arm 1), bortezomib 1 mg/m2 on days -9, -6 and -3(arm 2), and bortezomib 1.5 mg/m2 on days -9, -6 and -3 (arm 3). Primary endpoints were complete response (CR), NCI grade 4 toxicity, and overall survival (OS).

Results

In arms 1, 2 and 3, median intervals between diagnosis and auto HCT were 12.2, 9.6 and 8.8 months; median follow up in all surviving patients was 20 months (range 10 to 31). CR+near CR rates in arms 1, 2 and 3 were 35%, 30% and 25%. Grade 3–4 toxicity was seen in 6 patients in arm 1 (mucositis 3, dyspnea 1, acute renal failure 1, pleural effusion 1), 6 patients in arm 2 (mucositis 3, diarrhea 1, pneumonia 1 and hydronephrosis 1) and 6 patients in arm 3 (pulmonary edema 2, mucositis 1, intestinal obstruction 1, low back pain 1, elevated transaminases 1). The most common adverse events were nausea, diarrhea and pedal edema. Grade 1–2 weight gain due to fluid retention was seen in 84%, 70% and 95% of patients in arms 1, 2 and 3. Median time to neutrophil engraftment (ANC >500/dl) was 10 days in each arm. Median OS has not been reached in any of the 3 arms. Median progression-free survival (PFS) times were18.6, 13.2 and 17.5 months. OS was significantly shorter in patients with relapsed disease (0.00001) and cytogenetic abnormalities at auto HCT (0.0002).

Conclusions

Adding bortezomib to a preparative regimen of ATO, AA and high dose melphalan is safe and well tolerated in patients with multiple myeloma. There was no significant impact of adding bortezomib at either dose on the CR rate, grade 3-4 toxicity or OS.

Table:

Patient Characteristics and Outcomes

 Arm 1 (n=19) Arm 2 (n=20) Arm 3 (n=19) 
Median Age 61 59 64 
Abnormal Cytogenetics 2 (10%) 5 (25%) 8 (42%) 
Relapsed disease 6 (32%) 7 (35%) 3 (16%) 
Prior ASCT 
Months from Diagnosis to ASCT 12.2 9.6 8.8 
Median CD34 106/kg 4.2 4.1 3.6 
Median Days to Engraftment (ANC > 500) 10 10 10 
Maintenance Rx 6 (32%) 4 (20%) 3 (16%) 
CR + VGPR 7 (35%) 6 (30%) 5 (25%) 
Grade 3-4 AEs 
Median PFS (months) 18.6 13.2 17.5 
 Arm 1 (n=19) Arm 2 (n=20) Arm 3 (n=19) 
Median Age 61 59 64 
Abnormal Cytogenetics 2 (10%) 5 (25%) 8 (42%) 
Relapsed disease 6 (32%) 7 (35%) 3 (16%) 
Prior ASCT 
Months from Diagnosis to ASCT 12.2 9.6 8.8 
Median CD34 106/kg 4.2 4.1 3.6 
Median Days to Engraftment (ANC > 500) 10 10 10 
Maintenance Rx 6 (32%) 4 (20%) 3 (16%) 
CR + VGPR 7 (35%) 6 (30%) 5 (25%) 
Grade 3-4 AEs 
Median PFS (months) 18.6 13.2 17.5 
Disclosures:

Shah:Celgene, Amgen, Novartis, Elan: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Qazilbash:Cephalon: Speakers Bureau.

Author notes

*

Asterisk with author names denotes non-ASH members.