Targeting Patient at High Risk of Thrombocytopenia and Neutropenia with Cybord, Vel-Dex and VMP: Time to Decrease the Number of Blood Tests ?
Authors: Adam Jean-Philippe , Lemieux-Blanchard Emilie , Lemieux Bernard , Letarte Nathalie 
Published: October 2019

Abstract
Introduction Subcutaneous (SC) injection of bortezomib is more convenient for patients and staff. In September 2012, we standardised all bortezomib containing-protocols at our centre and changed the route of administration form intravenous to SC. Hematologic toxicity is commonly reported with these protocols. Currently, in our protocols, a complete blood count (CBC) is needed before every injection.
Objectives This retrospective study aimed to analyse the rate of neutropenia and thrombocytopenia with Vel-Dex, VMP and CyBorD based on a threshold at day 1 to see if a CBC is needed before every injection in all patients. Blood pressure (BP) was measured before and after each SC injection to evaluate the risk of hypotension.
Methods This retrospective study included all patients who received SC bortezomib in Vel-Dex, VMP and CyBorD protocols for multiple myeloma or amyloidosis at the Centre hospitalier de l'Université de Montréal (CHUM) between June 1, 2012 and May 31, 2013. Data was collected through medical and pharmaceutical patient records. Our local ethics board approved this study. Our main outcome is defined as the presence of neutropenia and thrombocytopenia for CyBorD (days 1, 8, 15 and 22 q 28 days), Vel-Dex (days 1, 4, 8 and 11 q 21 days) and VMP (days 1, 8, 22 and 29 q 42 days or days 1, 8, 15, 22 q 35 days) dichotomized at a threshold of ≥ 1.5 x 109 and ≥ 75 x 109respectively. A McNemar Test was used to estimate the association between the neutropenia and thrombocytopenia based on the dichotomized value on day 1.
Results A total of 69 patients received bortezomib for MM (65 patients) or amyloidosis (4 patients). Median age was 67 years (SD ± 9.1) and 58 % of patients were male. Patients received Vel-Dex (23.2%), VMP (36.2%) and CyBorD (40.6%) protocols in 1st line eligible to stems cells transplant (26.2%), 1st line non-eligible (40.0%) or ≥ 2nd line (33.8%) for a total of 349 cycles. The median starting dose of bortezomib was 1.3 mg/m2 (SD ± 0.14). As shown in tables I and II, there is a statistical evidence of association when neutrophils ≥ 1.5 x 109 and platelets ≥ 75 x 109 at day 1 with the minimum of neutrophils and platelets on the CBC for the rest of the cycle of CyBorD and VMP. For Vel-Dex no significant association was seen because the incidence of neutropenia and thrombocytopenia is very low and doesn’t depend on a threshold at day 1. A patient, who has values above this threshold at day 1, could receive the rest of the cycle (Vel-Dex, CyBorD or VMP) without additional CBCs. When patients had blood counts below this threshold, chemotherapy was delayed 18 times (generally at day 1) or cancelled 39 times (other days). Patient previously exposed to many lines of therapy tend to have lower neutrophils or platelets counts. Also, a total of 1224 BP values before after SC bortezomib were analysed. No significant difference was detected between the average systolic (122 vs 122; p=0.43) and diastolic BP (70 vs 71; p=0.33) before and after treatment. Hypotension, defined as a drop of 20 mmHg of systolic BP, occurred 37 times (3.0%) but systolic BP was never below 90 mmHg and treatment was not necessary. A small increase of heart rate (82 vs 84; p<0.001) was seen although it was not clinically significant.
Table I: Rate of neutropenia during the cycle according to day-1 neutrophil counts Protocols CyBorD VMP Vel-Dex Neutrophils at day 1 of each cycle n ≥ 1.5 n < 1.5 p value n ≥ 1.5 n < 1.5 p value n ≥ 1.5 n < 1.5 p value Neutrophils ≥ 1.5 for the rest of the cycle 81.8 % 20 % p<0.001 77.8 % 0 % p<0.001 95.5 % 100 % NS Neutrophils < 1.5 for the rest of the cycle 18.1 % 80 % 22.2 % 100 % 4.5 % 0 % TOTAL of cycle 121 25 - - - 117 7 - - - 67 2 - - -
Table II: Rate of thrombocytopenia during the cycle according to day-1 platelet counts Protocols CyBorD VMP Vel-Dex Platelets at day 1 of each cycle Plt ≥ 75 Plt < 75 p value Plt ≥ 75 Plt < 75 p value Plt ≥ 75 Plt < 75 p value Platelets ≥ 75 for the rest of the cycle 97.7 % 15.4 % p<0.001 83 % 33.3 % p<0.001 98.5 % 0 % NS Platelets < 75 for the rest of the cycle 2.3 % 84.6 % 17 % 66.7 % 1.5 % 100 % TOTAL of cycle 133 13 - - - 141 3 - - - 68 1 - - -
Conclusion Our results demonstrate that the rate of thrombocytopenia and neutropenia was very low in patients who have neutrophils and platelets ≥ 1.5 x 109 and ≥ 75 x 109 at day 1 of each cycle of Vel-Dex, VMP and CyBorD. In these patients, no CBC seems necessary for the rest of cycle. Decreasing the number of CBC will use less resources, decrease costs and most importantly, improve the patient’s care by minimising interventions without increasing risk of adverse events.

Disclosures
Adam: Janssen: Honoraria. Lemieux-Blanchard:Celgene: Honoraria. Lemieux:Janssen: Honoraria.