First Year Experience Of Subcutaneous Bortezomib Use In a University Teaching Hospital

Subcutaneous (SC) injection of bortezomib was reported to be safe and effective in myeloma patients. In September 2012, we standardised all bortezomib containing-protocols at our centre and changed the route of administration form intravenous (IV) to subcutaneous. This way of administration is more convenient for patients and staff and is reported to decrease the rate of peripheral neuropathies.

This retrospective study aimed to describe the safety of this new administration technique, specifically regarding change in blood pressure and hematologic toxicity. Blood pressure (BP) was measured before and after each SC injection to evaluate the risk of hypotension, an adverse reaction frequently reported with IV bortezomib administration. Secondly, we wanted to analyse the rate of neutropenia and thrombocytopenia during the treatment to see if a complete blood count (CBC) is needed before every injection, versus only once weekly. Other adverse events were also collected.

This retrospective study included all patients who received bortezomib for multiple myeloma or amyloidosis at the Centre hospitalier de l'Université de Montréal (CHUM) between June 1, 2012 and May 31, 2013. Date was collected through medical and pharmaceutical patient records. Our local ethics board approved this study.

A total of 45 patients received bortezomib for MM or amyloidosis with a median age of 68 years (SD ± 9.3) and 53.3 % were male. Patients received bortezomib in various protocols including Vel-Dex (42.2%), VMP (44.4%) and CyBorD (13.3%). The median starting dose of bortezomib was 1.3 mg/m² (SD ± 0.13).  Patients received  SC only bortezomib injections (71.1%) or IV only (15.6%)  or were switched from IV to SC (13.3%) for a total of 157 cycles (786 doses). A total of 444 BP values before and 425 BP values after SC bortezomib were analysed. No significant difference was detected between the average systolic BP (125 vs 125; p=0.76), diastolic BP (70 vs 71; p=0.77) or heart rate (79 vs 78; p=0.89) between the 2 measurements. Hypotension, defined as a drop of 20 mmHg of systolic BP, occurred 18 times (4.2%) but systolic BP was never below 90 mmHg. One patient had a severe dysautomia, possibly related to bortezomib that required the discontinuation of the treatment. At our center, CBC are performed prior to each bortezomib dose. Neutropenia occurred in 10 % of the total doses received. Risk factors influencing neutropenia were the use of oral alkylating agent (melphalan and cyclophosphamide) in the regimen and baseline neutrophil count less than 2.0 x 10⁹. Many patients also received bortezomib for a relapsed / refractory disease and were previously exposed to many lines of therapy. Thrombocytopenia occurred in 7,2% of doses received. Cutaneous toxicity occurred mostly with the first patients treated with the SC technique. With time, nursing changed their technique and further skin reactions were less reported. Neuropathy occurred in 21 patients (13 SC, 4 IV, 4 IV to SC), caused dose reductions in 7 patients (2 SC, 2 IV, 3 IV to SC) and treatment discontinuation in 2 patients (SC).

Our results demonstrate SC bortezomib was well tolerated. The rates of hypotension was quite low. Also rates and intensity of neutropenia and thrombocytopenia varied among different bortezomib containing regimens. Because of the low rate of profound neutropenia, Vel-Dex and VMP protocols can be modified to decrease the number of CBC to once weekly during the cycle rather than before every injection. More data are needed with CyBorD protocol before drawing any conclusions.

Adam:Jansen Ortho: Honoraria. Lemieux-Blanchard:Celgene: Honoraria. Lemieux:Jansen Ortho: Honoraria.