Co-existing chronic myeloid leukaemia and multiple myeloma: rapid response to lenalidomide during imatinib treatment

Abstract

We read with particular interest the recent case report by Ide et al. [1] and others [2–5] describing the rare occurrence of a patient with co-existent chronic myeloid leukaemia (CML) and multiple myeloma (MM). Here, we describe a further case in which CML and MM presented simultaneously, and in which commencement of imatinib was followed shortly by MM disease progression. A 71-year-old woman was referred to our department in August 2003 with leucocytosis, anaemia and thrombocytosis. She was asymptomatic and physical examination was unremarkable. Complete blood count (CBC) showed: haemoglobin (Hb) 9.3 g/dL, platelets 564 9 10/L, white cell count (WCC) 12.7 9 10/L with neutrophils 10 9 10/L. Bone marrow aspirate was hypercellular, and showed granulocytic hyperplasia without an increase in blasts. Furthermore, there was an infiltrate of atypical plasma cells accounting for 30% of nucleated cells. Serum protein electrophoresis showed an IgG kappa paraprotein band of 42 g/L with immune paresis. Renal function and serum calcium were normal, and serum b-2-microglobulin was elevated at 5.0 mg/L. Skeletal survey did not show any lytic bone disease. Anti-myeloma treatment was initially deferred, whilst other causes for anaemia were sought. Six months later, the patient’s WCC had risen to 37.2 9 10/L and cytogenetic analysis of a repeat bone marrow aspirate showed 46XX, t(9;22)(q34;q11) in all cell metaphases, confirming a diagnosis of CML. Treatment with imatinib 400 mg once daily was commenced and the patient responded rapidly, achieving a complete molecular remission after 9 months of treatment (measured by reverse transcriptase nested PCR sensitive to 1/10,000 dilution). However after 6-month treatment with imatinib, the patient’s IgG paraprotein had risen to 57.6 g/Lin keeping with MM disease progression. The patient received five cycles of melphalan and prednisolone, resulting in a marginal drop in serum paraprotein to 49.4 g/L. Thereafter, she received five complete cycles of bortezomib (1.3 mg/m) and dexamethasone, which was complicated by grade I peripheral neuropathy without any significant reduction in serum paraprotein, with a repeat bone marrow aspirate showing 60% plasma cells (see Fig. 1 for MM disease course). Thereafter, alternate day oral cyclophosphamide therapy resulted in frequent interruptions in treatment because of neutropenia without reduction in serum paraprotein level. At this point with the serum paraprotein at 50.8 g/L, lenalidomide and dexamethasone treatment was commenced, and the serum paraprotein fell to 9.1 g/L within 3 months (Fig. 1). Lenalidomide was commenced at a dose of 25 mg daily (21 from 28 days) for the first four cycles; however, significant neutropenia led to a dose reduction to 15 mg daily for cycle 5 and further to 5 mg daily from cycle 6 onwards. In addition, G-CSF was administered intermittently to maintain a neutrophil count [1.0 9 10/L but significant thrombocytopenia was not encountered. After 17 months of lenalidomide treatment, the dose was further reduced to 5 mg alternate days, on which she remains. Importantly, imatinib was continued throughout treatment with both lenalidomide and bortezomib, and the patient has maintained a complete molecular response to the present day. Our case is important for a number of reasons. Firstly, we believe this to be the first patient with both CML and MM who has been treated with both bortezomib and lenalidomide in combination with imatinib. Although her condition was bortezomib-refractory, the patient showed C. Offiah (&) J. P. Quinn P. Thornton P. T. Murphy Department of Haematology, Beaumont Hospital, Dublin 9, Ireland e-mail: chikaoffiah@gmail.com