Feasibility and Efficacy of Administration of Bortezomib-Containing Regimens to Patients Over the Age of 70 Years

Recent studies demonstrate superiority of bortezomib-containing regimens over standard therapy at improving response rates and durability of responses in patients with multiple myeloma (MM). However, limited data exist for the feasibility of delivering bortezomib-containing regimens to patients with MM over the age of 70 years. We therefore conducted a retrospective review of administration of bortezomib in combination with pulsed Dexamethasone (Bort-Dex) in elderly patients to determine the feasibility and toxicity of delivery.

Patients >70 years with MM who had received at least one prior line of treatment but had not been previously exposed to bortezomib, were assessed for their predicted tolerance to Bort-Dex: bortezomib 1.3mg/m² IV on days 1, 4, 8 and 11 (standard) on a 21 day-cycle or on days 1, 8, 15 and 22 (modified) on a 35 day cycle, in association with dexamethasone 20mg on the day of and day after bortezomib. Treatment was discontinued at maximal disease response, if refractory disease or if treatment-related toxicity precluded further cycles. A control cohort comprised patients <70 years matched for number of prior lines of therapy treated with Bort-Dex. International Myeloma Working Group response criteria and National Institutes of Health toxicity scores were used for assessments.

19 elderly patients with MM (IgG n=14; IgA n=2; light chain disease n=3) and a median age of 80 yrs (range 74, 90) were compared with 19 MM patients (IgG n=11; IgA n=3; light chain disease n=5) aged <70 yrs with a median age of 61 (range 39–70). Patients had received a median of 1 prior line of therapy (range 1, 4) in both cohorts. International staging system (ISS) scores ranged from 1 to 3 with a median of 2 in both cohorts. At diagnosis, in the elderly and control groups respectively, the median beta-2 microglobulin was 3.2 mg/l (range 1.8, 13) and 3.1 mg/l (range 2, 11.2), the median glomerular filtration rate was 49 mls/min/1.72sq.m (range 12, 69) and 71mls/min/1.72sq.m (range 14, 90), and median bone marrow plasmacytosis by flow cytometry was 13% (range 0.9, 51) and 17.2% (range 2.3, 36). Standard (n=12) and modified (n=7) dosing schedules were used in the elderly cohort, with standard dosing in the control cohort. Elderly patients received a median of 3 cycles (range 1–6) compared with a median of 4 cycles (range 1–6) in the control cohort (p=0.11).Response was not assessable in 4 patients: elderly n=3, control n=1. Response to Bort-Dex in the elderly and control cohorts, respectively: 5 (26%) and 6 (32%) patients achieved a complete response (CR) or stringent CR, 4 (21%) and 2 (11%) a very good partial response, 4 (21%) and 7 (37%) a partial response, 3 (16%) and 1 (5%) a minimal response or stable disease, 0 and 2 (11%) progressive disease. Median follow up was 5.1 months (range 0.6, 33.6) in the elderly and 12.1 months (range 0.7, 46.5) in the control cohorts. At last follow-up 7 (37%) patients in the elderly cohort had relapsed, with median time to progression (TTP) of 11.0 months (range 3.3, 16.8). In the control cohort 11 (58%) patients had relapsed with a TTP of 7.3 months (range 0, 21.3), p=0.26. In the elderly cohort, grade 3–4 haematological toxicity was reported in 2 patients (11%) with grade 3–4 non-haematological toxicity reported in 6 patients (32%): sensory neuropathy n=2, motor neuropathy n=1, fatigue n=2, infection n=2. Intensity of Bort-Dex was reduced in 5 patients, due to treatment-related toxicity. In the control cohort, grade 3–4 haematological toxicity was reported in 4 patients (21%) and grade 3–4 non-haematological toxicity in 5 patients (26%, sensory neuropathy in all cases). 2 elderly patients required hospital admission for treatment-related complications: cellulitis/varicella zoster reactivation (n=1; 23 days of admission) and bacterial sepsis (n=1; 41 days). By comparison, in the control cohort 1 patient required admission (15 days) for treatment of infective colitis. No treatment-related mortality was reported.

Reductions in the intensity and frequency of dosing are often required in order to deliver Bort-Dex to elderly patients, though with comparable response rates to younger patient populations. Through drug delivery modifications, Bort-Dex therapy can be delivered with an acceptable adverse event profile, offering a suitable salvage therapy for elderly patients with relapsed MM.

Cook:Orthobiotec: Consultancy, Speakers Bureau.