THE IMPORTANCE OF IMMUNOPHENOTYPIC COMPLETE REMISSION AFTER INDUCTION THERAPY IN PATIENTS WITH MULTIPLE MYELOMA ON PROGRESSION/RELAPSE FREE SURVIVAL

Background
Multiple myeloma (MM) is a malignant, essentially incurable desease caused by malignant transformation of B-lymphocytes. Depth of achieved remission appears to correlate with the duration of desease control. Therefore there are cumulative data supporting the importance of the molecularly or imunophenotypically defined remission (absence of minimal residual disease - MRD). MRD in bone marrow may be detected by flow cytometry (with a threshold sensitivity at a level of 1x10-4). Immunophenotypic complete remission (iCR) is defined by fulfilling requirements of conventional CR along with negative test of free light chains in serum and absence of myeloma cells  in the bone marrow by examination of at least 10? cells using > 4-color flow cytometry.

Aims
To verify the importance of iCR after induction therapy in patients with MM on progression/relapse free survival (PFS).

Methods
Retrospective analysis of 25 patients with MM consecutively diagnosed in 2010-2013, who achieved conventional CR after induction therapy and were examined by flow cytometry to evaluate eventual presence of MRD in bone marrow (according to EMN – European myeloma network).

Results
Our cohort of patients comprised 14 men and 11 women, the mean age was 60 years. Patients were treated with induction chemotherapy containing thalidomide in 12/25 (48%) and bortezomib in 13/25 (52%) and all patients subsequently received  highdose chemoterapy (HD-Melphalan 200 mg/m2) supported by autologous stem-cell transplantation.

A total of 8 patients (32%) in conventional CR after induction therapy achieved also iCR (the MRD-ve), while 17 patients (68%) had still by flow cytometry detectable MRD in bone marrow at a level of 1x10 to 1x10-2-4 (MRD +ve). Immunofenotypic data after autologous transplantation are not available. Between the two groups was no statistical difference in sex (p = 0.34),  cytogenetic risk group (p = 0.63), or type of induction chemotherapy (p = 0.73). The median PFS for MRD+ve was 23 months (12-48) and for MRD-ve  35 months (15-57), however difference in the median PFS between the two groups was not statistically significant (p = 0.73).

Summary
Our data indicated a trend towards a longer PFS for patients MRD-ve, however absence of statistical signification may be caused by the relatively low number of patients and eventually by the efect of subsequent HD-chemotherapy. The study with longer follow-up of more patients with flow cytometry-monitoring in all stages of treatment (also after HD-Melphalan) is thus waranted.

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