Bortezomib Administered Subcutaneously Is Well Tolerated in Bortezomib-Based Combination Regimens Used in Patients with Multiple Myeloma and AL Amyloidosis

Novel agents like the proteasome inhibitor bortezomib (Btz) and immunomodulatory agents show activity in multiple myeloma (MM) as well as in primary AL amyloidosis (AL). Btz has emerged as a standard of care in the treatment of patients with MM and AL. The approved dose and schedule of Btz is 1.3mg/m² administered on days 1, 4, 8, and 11 as an intravenous (i.v.) bolus injection. However, among several side effects, peripheral neuropathy (PN) has a particular negative impact on the quality of life of patients treated with Btz. A recent trial provided evidence for a similar efficacy of Btz administered subcutaneously (s.c.) compared to i.v. administration, but side effects including PN were significantly less frequent with s.c. application of Btz. Here we report our experience regarding efficacy and tolerability of treatment with Btz administered s.c. in patients with MM and AL.

19 consecutive patients with MM (n = 17) or histologically proven AL (n = 2) were included in this analysis. For s.c. administration, Btz was prepared at a concentration of 2.5 mg/mL (as opposed to an i.v. concentration of 1.0 mg/mL). All patients received Btz at a dose of 1.3 mg/m² on days 1, 4, 8, and 11. Btz was used in combination regimens with dexamethasone (n = 9), with thalidomide/dexamethasone prior to autologous transplantation (VDT; n = 6), or with melphalan/prednisolone in elderly patients (VMP; n = 4).

Patients (male n=7; female n=12) were at a median age of 64 years (range 38–77), and 11 patients (58%) received the Btz-based regimen with Btz s.c. as their first line treatment. At the time of analysis, a median of 3 cycles bortezomib s.c. (range, 1–5) have been administered. Hematological toxicities were only at Grades 1+2 and included anemia (78%) and thrombocytopenia (33%). Only one patient developed a grade 3 PN, and this patient already had pre-existing PN due to prior i.v. administration of Btz. Other non-hematologic side effects were at grades 1+2 including fatigue (11%) and local skin reactions at the site of s.c. injection, which were self-limited. No notable gastrointestinal toxicity was observed, and therefore we stopped the routine use of i.v. hydration and antiemetics, which were previously administered as concomitant therapy with i.v. Btz. Of 14 MM patients so far evaluable for response, 12 (86%) had a PR or better including 5 patients (36%) achieving a CR. Both patients with AL achieved a very good partial remission (VGPR). More data on efficacy with longer follow-up will be presented at the meeting.

Our observations confirm the improved toxicity profile of the s.c. administration of Btz in various standard Btz-based combination regimens. In addition, due to the ease of s.c. administration of Btz, patient management has been markedly facilitated at our centre.

No relevant conflicts of interest to declare.