Retrospective Study of the Efficacy and Safety of Treatment with Subcutaneous Injection of Bortezomib in De Novo Patients with MM

[Objective]

The induction therapy of multiple myeloma (MM) has dramatically changed due to the availability of new drugs such as bortezomib.To explore the efficacy and safety of subcutaneous injection of bortezomib in the treatment of de novo MM patients, a total of 56 patients treated with PAD form June 2008 to January 2015 were retrospective analyzed.

[Methods]

29 patients in PAD group received intravenous injection of bortezomib 1.3mg/m2, d1,4,8,11, Adr iv 40mg/m2, d1, Dex iv 20mg, d1,2,4,5,8,9,11,12; another 28 in improved PAD group received subcutaneous injection of bortezomib1.3mg/m2, d1,4,8,11, Adr iv 40mg/m2, d1, Dex iv 20mg, d1,2,4,5,8,9,11,12. The efficacy and safety of two groups were analyzed.

[Results]

The response rate >= VGPR after 4 cycles of PAD or improved PAD were 51.7% and 51.9% respectively.With a median follow up of 24 months,the median TTP , PFS and OS of the PAD group was 47 months, 42 months, 63 months respectively, but the time of the improved PAD group wasn't shown up yet.In the improved PAD group,2y- TTP ,PFS and OS was 94.4%, 94.4%, 100%. With a follow-up to 60 months,the OS of standard-risk group[without FISH 1q21+, or t(4;14), or p53-]was 61.9%,but the survival was only 31.9% in FISH high-risk group. OS, PFS of the patients with 1q21 amplification was 18.7-56.4 months and 9.7-53.5 months, showed statistical difference (P=0.029), (P=0.037), compared to FISH negative patients,which was 51.5-71.3 months and 39.4-68.4 months. The study found that the hemoglobin < 100 g/L or 1q21⁺ were the poor prognosis factors for patients' OS, while subcutaneous injection of bortezomib could improve OS(P=0.042), mainly because compared to PAD group,Grade 3 or worse adverse events were significantly reduced in improved PAD group. the most common were peripheral neuropathy (P=0.049), infection(0.004). When α=0.1, leukopenia(P=0.086), diarrhea(P=0.093) also showed statistically significant difference.

[Conclusions]

The improved PAD regimen by changing bortezomib from intravenous administration to subcutaneous injection significantly reduced adverse events, improved the safety of clinical application of bortezomib without affecting curative effect, and had greatly improved the OS.1q21 amplification was the poor prognostic factors in PAD induction treatment of MM.