The Addition of Meloxicam to G-CSF Is Associated with Good Mobilization Rates, Faster Engraftment and Reduced Toxicity and Hospital Stay after Autologous Stem Cell Transplantation – a Phase II Study
Authors: George Biju , Viswabandya Auro , Alex Ansu Abu , Lakshmi Kavitha M , Abraham Aby , Ganapule Abhijeet , N Fouzia , Srivastava Alok , Mathews Vikram 
Published: November 2019

Abstract

Mobilization failure is seen in 10-15% of patients undergoing G-CSF or Chemo mobilization and the use of plerixafor is limited by its cost in developing countries. This phase II study is being undertaken to study whether the addition of Meloxicam to standard G-CSF will improve rates of mobilization (CTRI/2014/06/004671). After informed consent, patients received Meloxicam 15 mg once daily for 5 days from Day -7 to -3 and G-CSF 5 ug/kg BD from Day -4 to -1. Peripheral blood stem cell harvest was performed on Day 0 and on the following day is the initial harvest CD34 dose was < 4 x 106 CD34/Kg. Patients with myeloma proceeded immediately to an autologous transplant (auto SCT) with Single agent Melphalan conditioning while patients with lymphoma and acute myeloid leukemia had cryopreservation of harvest and then proceeded with transplant using either BEAM or BuCy2 conditioning.
Between November 2013 till July 2014, 25 patients (20 males and 5 females) with a median age of 51 years (range: 25-63) received meloxicam with G-CSF. There was no toxicity in any of the patients during the 5 days of administration of meloxicam. A cell dose of > 2 x 106 CD34/kg was achieved in 21 (84%) with a cell dose of > 3 x 106 CD34/kg being achieved in a single harvest in 15 (60%). Four patients needed additional cyclophosphamide mobilization to achieve the target cell doses. Analysis of peripheral blood CD34 counts revealed that 20 (80%) had counts > 20/ul on Day 0 [median count of 65.5/ul (range: 21.1 – 313.02) and of these 15 (60%) had achieved counts of > 20/ul on Day -1 itself [median count of 45.3/ul (range: 21.4 – 130.2)]. None of the patients had toxicity related to meloxicam. Subsequently 21 patients underwent auto SCT and their data was compared with 50 age and disease matched controls who had mobilization and auto SCT at our centre between January 2013 and March 2014. Though mobilization rates and cell doses were not significantly different, the use of meloxicam and G-CSF was associated with faster neutrophil engraftment. Following auto SCT, there was lower Grade III – IV toxicity, lower transfusion requirement of red cells and reduction in the duration of hospital stay post SCT [Table 1].
Conclusion: The addition of meloxicam to G-CSF improves stem cell mobilization and is associated with faster engraftment, no additional toxicity, lower supportive care and lower duration of hospitalization. It is also potentially possible that we may be able to harvest the patients a day earlier depending upon the peripheral blood CD 34 counts achieved. This data warrants a prospective randomized trial comparing Meloxicam + G-CSF with G-CSF alone as a mobilization strategy prior to autologous stem cell transplantation.
Table 1 – Comparison of demographic data, mobilization characteristics and post transplant outcome in patients using meloxicam + G-CSF compared with historical controls Abstract 2455. Table 1VariablesMeloxicam + GCSF (n = 25)G-CSF alone (n = 50)P valueMedian age (years)51 (25 – 63)50 (18 -65)0.902Sex M: F20: 536:140.577Diagnosis MM NHL/HD APML/AML15 (60%) 8 (32%) 2 (8%)32 (64%) 14 (28%) 4 (8%)Successful mobilization (> 2 x 106 CD34/kg after 2 harvets)21 (84%)42 (84%)1.000CD 34 > 5 x 106 /kg12 (48%)18 (36%)0.138CD 34 > 3 x 106/Kg20 (80%)32 (64%)0.191Conditioning regimen High dose Melphalan BEAM Bu/Cy215 (60%) 8 (32%) 2 (8%)32 (64%) 14 (28%) 4 (8%)ANC > 500/cumm (days)11.09 + 0.5311.53 + 0.920.044ANC > 1000/cumm (days)11.61 + 0.4511.95 + 0.990.216Platelet count >20000/cumm (days)14.7 + 4.516.4 + 6.30.291Platelet count >50000/cumm (days)17.4 + 7.524.7 + 19.30.143Platelet count >100000/cumm (days)23.1 + 11.951.2 + 58.20.025Number of red cell units transfused1.19 + 1.12.31 + 2.450.031Number of platelet units transfused12 + 9.117 + 160.327No of pts with Grade III-IV toxicity7/21 (31.8%)33/47 (59.5%)0.040Duration of hospital stay from day 0 (days)16 + 3.320 + 7.30.025

Disclosures
Srivastava: Octapharma: Consultancy, Other.