Subcutaneous Bortezomib in Multiple Myeloma Patients Induces Similar Therapeutic Response Rates as Intravenous Application But It Does Not Reduce the Incidence of Peripheral Neuropathy

Abstract

ObjectiveSubcutaneous (SC) application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM) patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM) patients treated using either intravenous (IV) or subcutaneous (SC) route of administration.Patients and methodsDuring January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly – 63% or twice weekly – 27%) in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.ResultsThe response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN). PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥2 was present in 20% vs 18% and PN grade ≥3 was present in 6% vs 4%.ConclusionsWe conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.

Characterization of a rat model of bortezomib‐induced painful neuropathy

“…The site of subcutaneous administration, thigh or abdomen, was also shown not to affect pharmacokinetic and pharmacodynamic parameters (Moreau et al, ; Moreau et al, ). There does not appear to be an agreed consensus regarding neuropathy incidence and administration routes, with studies reporting contrasting results (Moreau et al, ; Arnulf et al, ; Minarik et al, ), suggesting that neuropathy prevalence is primarily linked to dosage. One animal study has administered Velcade® subcutaneously (Bruna et al, ); however, this study had a high cumulative dose (12 mg·kg −1 ).…”

Phase II study of bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial

“…This has resulted in widespread adoption of subcutaneous bortezomib. Bortezomib dose reductions and once‐ versus twice‐weekly regimens have also been shown to decrease associated rates of polyneuropathy (Palumbo et al , ; Minarik et al , ), potentially as a consequence of patients receiving a lower cumulative dose.…”

Peripheral neuropathy associated with subcutaneous or intravenous bortezomib in patients with newly diagnosed myeloma treated within the GMMG MM5 phase III trial

“…15 The majority of patients were treated with weekly instead of twice-weekly bortezomib in the respective study, 15 which underlines the fact that not only route of administration but also dose intensity influences development of PN. Although the route of administration might be less important for the occurrence of BiPN in newly diagnosed patients receiving short-term treatment, we still recommend SC administration, since other non-PN AEs occur less frequently.…”

“…Occurrence of PN during therapy has no negative impact on treatment response. Peter Brossart, 10 Christian Gerecke, 11 Hans-Walter Lindemann, 12 Matthias Zeis, 13 Katja Weisel, 14 Jan Duerig 15 and Hartmut Goldschmidt …”