PB1998: WEEKLY OPPOSED TO BI-WEEKLY BORTEZOMIB AS PART OF INDUCTION CHEMOTHERAPY IN NEWLY DIAGNOSED MULTIPLE MYELOMA IS BETTER TOLERATED AND EQUALLY EFFICIENT: REAL-WORLD DATA FROM A RETROSPECTIVE AUDIT

Abstract

Background: The VTD (Bortezomib, Thalidomide, Dexamethasone) triplet chemotherapy regime is frequently used as induction chemotherapy in newly diagnosed multiple myeloma prior to autologous stem cell transplant. The manufacturer’s protocol recommends a twice-weekly dosing schedule. Adverse effects are common, most notably neuropathy and cytopenias. These can be disabling and are often permanent, with significant impacts on quality of life. This limits drug tolerance with management confined to dose reduction or discontinuation. A once-weekly dosing schedule has been widely adopted, but to date, no clinical trials have been conducted to compare the efficacy and side effect profile of this dosing frequency in transplant-eligible myeloma. Aims: In order to investigate prescribing practice locally, we conducted a retrospective audit in Leicester Royal Infirmary, a tertiary Haematology centre in the UK. Primary outcomes were response to induction therapy, and the development of neuropathy (peripheral or autonomic) or serious adverse events occurring whilst on VTD. Secondary outcomes included cumulative Bortezomib dose, number of Bortezomib cycles and Thalidomide tolerance. Methods: Real-world data was collected consecutively from all patients treated in the intensive treatment arm with VTD as first-line chemotherapy between January 2015 and November 2020. Patient received Bortezomib 1.3mg/m2 subcutaneously on days 1,4,8 and 11 of a 21-day cycle (bi-weekly) or days 1,8,15 and 22 of a 35-day cycle (weekly). The trust protocol was altered in December 2020, increasing the bi-weekly regime to a 28-day cycle Results: We demonstrate a trend of lower incidence of neuropathy, both peripheral and autonomic, with the weekly regime (PN≥2: weekly 8.7% bi-weekly 19.6% AN: weekly 8.7% bi-weekly 26.5%). There was also a trend of fewer serious adverse events with lower rates of hospital admissions due to infection (weekly 33.3% bi-weekly 47.8%). Patients on the weekly regime received more VTD cycles and a higher cumulative dose (p=0.044). The initial therapeutic response between the two regimes were similar (weekly: ORR 87% ≥VGPR 78.3%, bi-weekly: ORR 86.3% ≥VGPR 60.8%). Preliminary data from patients treated with bi-weekly Bortezomib in a 28-day cycle shows lower rates of peripheral neuropathy compared to the 21-day cycle. Image:Summary/Conclusion: Here we demonstrate that weekly Bortezomib is better tolerated with equal efficacy in terms of initial therapeutic response. We believe that delivery of Bortezomib through a weekly regime facilitates patients being able to maintain on Bortezomib longer and receive higher cumulative doses. This may have important implications in those later deemed unsuitable or transplantation and for future treatment as intolerance or refractoriness limits the ability to obtain Bortezomib in further treatment lines. Preliminary data shows the cycle length may also be important in determining the risk of side of side effects and we intent to continue to monitor patients treated with this regime.