Partial Efficacy of Bortezomib on Acute Myeloid Leukemia (AML) Cells in a Patient with Concomitant Multiple Myeloma and AML.

Bortezomib has a well known efficacy in multiple myeloma, but effects on AML cells is only observed in vitro and remain to be clinically proved. In a 78 year-old patient, we diagnosed two concomitant aggressive hematological malignancies: IgA Kappa multiple myeloma and de novo FAB-M5 AML. The patient was consulting for bone pain and progressive bicytopenia. The bone marrow was infiltrated with 30% dystrophic plasmocytes and 35% myeloïd monoblastes with CD13+, CD33+ phenotype. A serum M component of 5 g/dl IgA kappa was present at diagnosis with mild acute renal failure, elevated beta2microglobulinemia and IPSS score of 2. The cytogenetic study revealed poor prognosis factors for both malignancies with a complex caryotype including chromosome 13 abnormalities and MLL rearrangement. Standard treatments to cure both diseases one after the other could not be a good option, due to the presence of these poor prognosis factors. Thus, we decided to treat the patient with Bortezomib, a proteasome inhibitor known to induce clinical response in multiple myeloma and apoptosis of leukemia cell lines in vitro. After two cycles of Bortezomib (1.3 mg/m² day 1,4,8,11) combined with steroids (dexamethasone, 40 mg day 1–4), the patient obtained a near complete myeloma remission with normal electrophoresis, but also disappearance of circulating AML blast and a 70% reduction of medullary AML blasts. Low-dose cytarabine (15 mg twice the day for 10 days) was introduced after the fourth cycle of bortezomib because of persistent circulating AML blasts. Bortezomib was stopped after 5 cycles because of neurological adverse event. After 5 cycles of cytarabine, the patient reached complete cytogenetic remission of both diseases. The patient still remains in complete remission after 13 months of follow-up. We conclude that bortezomib had a partial efficacy on AML cells in vivo and could have synergized with cytarabine to reach and maintain complete remission of both poor prognosis AML and multiple in this patient.