Up-front fludarabine impairs stem cell harvest in multiple myeloma: report from an interim analysis of the NMSG 13/03 randomized placebo controlled phase II trial

Abstract

The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conclusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim toxicity and safety analysis, the trial was stopped following inclusion of 34 of a planned 80 patients due to a reduced number of patients (4/17) actually harvested in the experimental arm compared to the control arm (11/17; p<0.05). In conclusion, the scheduled fludarabine dosage in 2 cycles combined with alkylating therapy impairs stem cell mobilization and standard therapy in young MM patients and should not be administrated up-front.

Multiparametric flow cytometry profiling of neoplastic plasma cells in multiple myeloma

“…All patients were above 18 years of age and were referred to the departments for diagnostic evaluation. The patients were included in clinical trials based on high‐dose melphalan and autologous stem cell transplantation (26–32) and laboratory studies published (37–55).…”

“…The diagnosis of MM was accepted if criteria A + C, A + D, or B + C + D of the following were fulfilled: (a) serum monoclonal component (M‐protein) concentration of immunoglobulin (Ig)G > 30 g/l, IgA > 20 g/l, the presence of an M‐protein of IgD or IgE regardless of concentration, or Bence‐Jones proteinuria > 1 g/24 h; (b) M‐protein in serum or urine at a lower concentration than described under A; (c) at least 10% PCs in BM aspirate or biopsy‐verified plasmacytoma of bone or soft tissue; and (d) osteolytic bone lesions (26–32).…”

“…Here, we report the results from such an analytic strategy (laboratory protocol NMSG 9/99) retrospectively performed on data from sequentially analysis of samples from newly diagnosed MM patients from Denmark, Norway, Sweden, and Finland included in published clinical trials within NMSG (26–32).…”