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KOS 2007: Response by SFLC and Marrow Flow Cytometry in MRC Myeloma IX
Roger Owen, MD
HMDS Laboratory and Department of Haematology
Leeds Teaching Hospitals
Leeds, UK
06.27.07

AUTHORS: R.G. Owen,1,2 A.C. Rawstron,1 F.E. Davies,3 S. Bell,4 K. Cocks,4 G. Cook,2 A.J. Ashcroft,2 G. Jackson,5 G.J. Morgan,3 J.A. Child,1,2,4 M.T. Drayson6
1HMDS Laboratory and 2Department of Haematology, Leeds Teaching Hospitals; 3Department of Haemato-oncology, Royal Marsden Hospital; 4Clinical TrialsResearch Unit, University of Leeds, 5Royal Victoria Infirmary, Newcastleand 6Myeloma Clinical Trials Unit, University of Birmingham, UK

Introduction. In the intensive pathway of the Medical Research Council Myeloma IX trial younger patients (those suitable for high dose therapy) are randomized between two induction schedules namely CVAD and CTD. All responding patients then receive high-dose melphalan (200mg/m2) with stem cell support and are subsequently randomized to no further therapy or maintenance with thalidomide (50-100 mg daily). The purpose of this preliminary evaluation was to determine the applicability of the serum free light chain (SFLC) assay and bone marrow flow cytometry in assessing response to therapy and determine their merits in comparison to conventional response assessment using serum and/or urine paraprotein estimations. Materials and methods. To date (19/01/07) 1007 patients have been enrolled in the intensive pathway of Myeloma IX and 349 have undergone the second randomization to thalidomide maintenance or observation. SFLC as well as standard serum and urine paraprotein assessments were performed in a central reference laboratory at the following time points: presentation, following 3 cycles of induction, end of induction, 6 weeks and 3 months post high-dose therapy and 3 monthly thereafter until relapse. Similarly multiparameter flow cytometric evaluation of plasma cells was evaluated (again in a central laboratory) at presentation, at the end of induction and day 100 following high-dose therapy and annually thereafter until relapse. Results. Preliminary assessment has confirmed the general applicability of the SFLC assay including virtually all patients with light chain disease and approximately 65% of patients with non-secretory disease. Similarly aberrant plasma cell phenotypes (based on expression of CD19, CD56 and CD45) were demonstrable in >95% of patients with assessable bone marrows. The SFLC provided for a more rapid assessment of response to induction therapy compared to standard paraprotein estimations and provided an early identification of patients with refractory disease. Flow cytometry was more valuable in determining complete responses to both induction and high-dose therapy as conventional assessment was influenced by the long half life of the paraprotein in many patients. Conclusions. The SFLC assay and multiparameter flow cytomeric assessment of plasma cell numbers allow for a more rapid and detailed assessment of response in patients receiving intensive sequential therapy.


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