Subcutaneous administration of bortezomib significantly decreased and delayed the development of peripheral neuropathy in patients with newly diagnosed multiple myeloma

Abstract

Bortezomib (btz) is the major and potent agent in multiple myeloma (MM) treatment and intravenous (IV) injection is its standard administration route. However, peripheral neuropathy (PN) always limited the use of btz. Subcutaneous (SC) administration is an important alternative. The primary outcome of our previous study showed that SC administration of btz significantly decreased and delayed the development of PN in patients with newly diagnosed MM (NDMM) and relapse/refractory MM (RRMM). Here, we amplified the cohorts and extended follow up to further confirm our previous primary outcome in patients with NDMM. This retrospective, historical control study was undertaken at a single centre in China. Patients with NDMM were assigned to receive up to nine 21-day cycles of Btz based regimens, including PAd/VDd/BCd (btz 1.3 mg/m2 , on days 1, 4, 8 and 11; adriamycin 9 mg/m2 on days 1-4; or PLD 30mg/m2 on days 1, or CTX 500mg/m2 on days 1, 8, 15, and dexamethasone 20 mg/day on days 1, 2, 4, 5, 8, 9, 11 and 12). Btz was administered by SC injection or IV infusion. Then the efficacy and safety of SC versus IV btz were compared. 330 NDMM patients were received Btz based treatment. 151 received a median of 5 cycles of SC btz (SC group) from 2012.3 to 2014.12. 179 cases were treated with a median 3 cycles of IV btz (historical control IV group) from 2008.5 to 2012.2. The overall response rate (ORR, >1⁄4PR) was 97.4% and 97.2% in these two groups, with 37.7% and 36.3% achieved CR respectively, indication the efficacy was very comparable. SC group had better safety profile. Most of any grade adverse events (AE) were less common with SC than with IV administration, including thrombocytopenia, neutropenia, anaemia. The most importance was PN of any grade (32.1% vs 58.1%; p1⁄40$01) was significantly decreased with SC btz. Especially severe PN (grade 3/4) was also significantly decreased (5.3% vs 18.4%, p1⁄40.013). Notably, the incidence and seriousness of diarrhea were lower (any grade, 9.8% vs 15.7%, >1⁄4grade 3, 0.9% vs 4.7%, respectively), so were constipation, and intestinal obstruction, which may be related to the neuropathy toxicity of btz. The time of developing PN was delayed in SC group. Median dosage of btz when PN developed was 15.6 mg/m2 in SC group and 10.4mg/m2 in IV group. The efficacy of SC btz in patients with NDMM was comparable with standard IV administration. SC btz was locally well tolerated. It significantly decreased and delayed the development of PN. PO-143 Melphalan 140mg/m“2” significantly reduces 5 year progression free survival in multiple myeloma patients receiving a peripheral blood autologous stem cell transplant compared with melphalan 200mg/m“2” C. Attwood, E. Nicholson, R. Chakraverty, A. Fielding, P. Kottaridis, D. Hughes, A. Mehta, W. Stewart, C. Kyriakou, S. Worthington, S. Grace, A. Wechalekar, S. MacKinnon Royal Free Hospital, London