Hematological Testing Is Not Required with Every Dose of Bortezomib In Patients with Adequate Blood Counts at the Start of Each Cycle
Authors: Raibagkar Pooja S. , Richardson Paul G , Sonneveld Pieter , Schuster Michael W. , Irwin David , Stadtmauer Edward A. , Facon Thierry , Harousseau Jean-Luc , Ben-Yehuda Dina , Lonial Sagar , Goldschmidt Hartmut , Reece Donna E. , Miguel Jesus F San , Blade Joan , Boccadoro Mario , Neuwirth Rachel , Esseltine Dixie-Lee , Anderson Kenneth C. , Munshi Nikhil C. 
Published: October 2019

Abstract
Abstract 1963

Introduction:
Bortezomib has significant activity in patients with multiple myeloma (MM) but can be associated with hematological toxicity. Based on this initial concern, patients (pts) receiving a standard dose and schedule of Bortezomib, twice a week for two weeks, are typically required to be evaluated for adequate blood counts before each bortezomib infusion. This prerequisite substantially increases the time patients need to be in the clinic putting both patients as well as health care providers at potentially increased inconvenience. In an effort to make bortezomib administration more convenient, we evaluated the need for monitoring complete blood counts (CBC) before each infusion by examining for any predictable changes in blood counts on days 4, 8 and 11, based on day 1 counts.

Methods:
We investigated the changes in neutophil and platelet counts in pts treated with bortezomib on the phase 3 APEX (Assessment of Proteasome Inhibition for Extending Remission) study. Pts with MM and measurable disease following 1 to 3 prior therapies were randomized to receive bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 for eight 3-week cycles, then on days 1, 8, 15, and 22 for three 5-week maintenance cycles, or dexamethasone 40 mg on days 1 to 4, 9 to 12, and 17 to 20 for four 5-week cycles, then days 1 to 4 for five 4-week cycles. Platelet count (Plt) and absolute neutrophil count (ANC) were recorded throughout, and incidences of thrombocytopenia and neutropenia were calculated.

Results:
Data from all 319 pts receiving bortezomib on this study have been analysed. In this relapsed pt population, 15% of pts had plt counts <100 ×109/L on day 1 of cycle 1. However, by cycle 1 day 11, 43% were below this limit; similarly an ANC <1.5×109/L on day 1 of cycle 1 was observed in 13% and on day 11, in 27%. To evaluate the need for CBC prior to every dose we then analyzed the shift in blood counts from day 1 of cycles 2–4 relative to days 4, 8, and 11 of each cycle. We observed that all pts with Plt ≥100 ×109/L on day 1 of cycles 2, 3, and 4 had Plt ≥20 ×109/L on Day 4, and 8; and 99% on day 11. Importantly none of the patients with plt count > 100 ×109/L on day 8 of cycles 2–4, had their plt count drop below 20 ×109/L on day 11. Similarly pts with ANC ≥ 1.5×109/L on day 1 of each cycles 2–4 had ANC ≥ 0.5 ×109/L on days 4, 8, and 11 in > 99% pts. It is also important to note that responding pts had higher counts on day 1 of each cycle and had a lesser drop in their Plt count and ANC with each treatment.

Conclusions:
These results suggest that the change in CBC with bortezomib treatment as monotherapy is predictable. Importantly, CBCs done on day 1 of cycle 2 and beyond were able to predict the chance of thrombocytopenia and neutropenia on days 4, 8, and 11. We would suggest that patients with a plt count > 100 ×109/L and ANC > 1.5 ×109/L on day 1 of cycle 2 and beyond may not require rechecking of CBCs on days 4, 8 and 11. Reducing the number of CBC's needed during each cycle may improve patient compliance and save time both for pts and health care providers as well as improve resource utilization.

Disclosures:
Richardson: Millenium: Membership on an entity's Board of Directors or advisory committees. Sonneveld:Celgene: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Harousseau:Millenium: Membership on an entity's Board of Directors or advisory committees. Lonial:Millennium, Celgene, Bristol-Myers Squibb, Novartis, Onyx: Advisory Board, Consultancy; Millennium, Celgene, Novartis, Onyx, Bristol-Myers Squibb: Research Funding. Reece:Celgene: Honoraria, Research Funding. San Miguel:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen-cilag: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees. Blade:Millenium: Membership on an entity's Board of Directors or advisory committees. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Neuwirth:Millennium Pharmaceuticals, Inc.: Employment. Esseltine:Millennium Pharmaceuticals, Inc.: Employment; Johnson & Johnson: Equity Ownership. Anderson:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Onyx: Consultancy; Merck: Consultancy; Bristol Myers Squibb: Consultancy; Acetylon: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Munshi:Millennium Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees.