Weekly Subcutaneous Bortezomib Is Well Tolerated and Effective As Initial Therapy Of Symptomatic Myeloma

Bortezomib became funded in New Zealand for first line therapy of myeloma in May 2011. In June 2011 North Shore and Christchurch Hospitals moved to weekly subcutaneous use. We performed a retrospective review of all untreated symptomatic myeloma patients presenting to North Shore and Christchurch Hospitals. Patients were treated with CyBorD consisting of Cyclophosphamide 300mg/m² PO, Bortezomib 1.5 mg or 1.6mg /m² SC (at 2.5mg/ml) and Dexamethasone 40mg PO, administered weekly. Four weeks was called one cycle. Transplant eligible patients received 4-6 cycles prior to transplant with melphalan 200mg/m², with stem cell mobilization after the 4^th cycle. At North Shore consolidation was given with 3-4 cycles of VTD starting day 100 consisting of Bortezomib 1.6mg/m²SC, Thalidomide 100mg PO and Dexamethasone 40mg. Non-transplant eligible patients were treated with a similar schedule but omitting the transplant, i.e. CyBorD x 5, VTD x4. In older patients treatment was stopped earlier.

From 9^th May 2011 to 8^thJuly 2013, 105 patients (55 transplant eligible and 50 non-transplant eligible) with untreated symptomatic myeloma (IgG 62, IgA 19, light chain 19, IgD 4, mixed 1) received CyBorD. Steroid pretreatment was given to 25 pts. The median age was 67 years (range: 38 to 89 yrs). ISS was available in 80 pts and was 1 in 35%, 2 in 36% and 3 in 29%. Creatinine was > 200 µmol/l in 16 pts and dialysis was needed in 6 pts, using high-cut off filters in 2pts. At presentation 27 patients had hypercalcaemia >2.7 mmol/L.

At a median follow-up of 8 months (range 1 to 26 months), the Kaplan-Meier estimate of OS was 93% (± 3%) at 1 year and 88% (± 5%)at 2 years. Disease free survival was 82% (± 5%) at 1 yr and 60% (± 10%) at 2 years. There was a non-significant trend for better PFS in transplant eligible patients with 1 yr PFS 91% vs 82% and 2 yr PFS 66% vs 52%(log rank p=0.149), in transplant eligible and ineligible pts , respectively. Data on response was available for 98 patients. Overall response rate of ≥ PR was 95%, with a median time to response of 36 days. Time to PR was the same for transplant eligible and non-eligible patients (log rank p=0.56). VGPR was achieved in 59pts, with Kaplan-Meier estimates of VGPR 74% (± 6%) at 1 yr and 77% (± 6%) at 2 years. CR rates improved progressively with time, 16 patients achieved CR with Kaplan-Meier estimate of CR 25% (± 6%) at 1 yr and 34% (± 8%) at 2 years. Treatment was well tolerated. There were 8 patients who had dose reduction due to neuropathy. Painful neuropathy was rare.

Of the 55 transplant eligible patients, so far 36 have proceeded to transplant, 8 have transplant planned, and 11 have not been transplanted due to: progressive disease (2 pts), failure to mobilise (3 pts), patient choice (3 pts), and comorbidity (3 pts). The overall success rate of proceeding to transplant was high at 76% (36/47 pts), compared to other population studies. Of the 36 patients who proceeded to transplant the overall response pre-transplant was 92% (CR 3, VGPR 14, PR 16, SD 2, NR 1). This improved to 100% in 35 pts assessable post transplant (CR 8, VGPR 16, PR 11). Following transplant 18 patient have receive a median of 3 cycles VTD consolidation (Range 1 to 5). The overall survival following transplant is 100% at 2 yrs, PFS was 97%(± 3%) at 1yr and 79% (± 15%) at 2 years, with no difference yet in those receiving consolidation (1pt progressed compared to 2 in those who did not receive consolidation, Breslow p=0.13). The 1 yr Kaplan-Meier estimates of PR 100%, VGPR 75%(± 9%)and CR 28% (± 9%) increased to VGPR 88% (± 8%) and CR 39 % (± 10%) at 2 years.

In this unselected cohort, treatment with weekly subcutaneous bortezomib, as part of CyBorD or VTD, was well tolerated even in elderly patients. Neurotoxicity was low and responses are excellent and durable. Post-transplant consolidation is well tolerated but it is too soon to see if this improves PFS. Weekly subcutaneous bortezomib seems better tolerated than IV, with no evidence of reduced efficacy compared to previously published reports.

No relevant conflicts of interest to declare.