Lenalidomide on alternative days is effective in myelodysplastic syndrome with 5q‐ deletion

Abstract

Lenalidomide is the treatment of choice in low-risk patients with myelodysplastic syndrome (MDS) and 5q- deletion, at the standard dose of 10 mg for 21 d of every 28-d cycle (Giagounidis et al, 2008). The main response criteria is to achieve blood transfusion independence and recent data reported a response rate of more than 60% in this subset of patients (Jädersten & Hellström-Linderberg, 2009). Nevertheless this effective treatment frequently induce severe (World Health Organization grade III–IV) neutropenia (55% of treated patients) and thrombocytopenia (44% of patients) at least during the initial 2–3 months. Another problem to be considered is the high cost of this standard therapy, as recently highlighted (Stone, 2009). One way to reduce toxicity has been reported by lowering the standard dose from 10 to 5 mg/d for 21 d (Giagounidis et al, 2008), but this schedule did not substantially affect the cost, because of the tablets’ unit price. On this particular issue we would like to report our pivotal experience in six patients treated with lenalidomide at 10 mg on alternative days for 21 d every 28 d. Our intent was to maintain the same efficacy, reduce treatment-related toxicity and also lower the cost of treatment. Moreover, there are no published data to date about the target plasma concentration of lenalidomide required to effectively inhibit the del 5q clone (Kelaidi et al, 2008). Patients signed an informed consent before starting this modified drug schedule. Their characteristics and response to lenalidomide are summarized in Table I. All six patients were blood transfusion-dependent (Haemoglobin level ranging from 70 to 85 g/l) after failing erythropoietin (EPO). Blood values included also mild leucopenia (range white blood cell count ranged from 2 to 4 × 109/l) and a normal/slightly high platelet count (range 280 to 450 × 109/l). All patients started lenalidomide with a normal creatinine clearance (90–125 ml/min) and no serological abnormal value, apart from an elevated ferritin level (range 520–1900 μg/l). No other treatment except EPO and red cells support was previously given to the patients. After receiving lenalidomide at 10 mg/d on alternative days for 21 d every 28 d, all six patients achieved transfusion independence within 3 months (three patients) and within 4 months (three patients) from starting the treatment, respectively. At the time of this report the last haemoglobin level of the patients ranged from 110 to 143 g/l after a median time of treatment of 11 months (range 6–14 months) (Table I). Five out of 6 patients were evaluated for cytogenetic response (CyR): 2/5 patients achieved a complete cytogenetic response (CCyR) after 7 and 6 months of treatment, respectively, while 3/5 patients obtained a partial CyR (with residual 5q- mitosis ranging from 20% to 25%) after 7, 8 and 9 months of treatment, respectively. CyR was confirmed in all patients at last follow-up. Regarding drug-related toxicity, only 1/6 (17%) patients experienced a grade 3 thrombocytopenia, while 2/6 (33%) patients had grade 3 neutropenia, which needed a short course of granulocyte colony-stimulating factor treatment. None of the patients had fever or infection and no further dose reduction was applied. To our knowledge, this is the first report suggesting that 10 mg lenalidomide on alternative days is as effective and possibly less toxic than standard 10 mg/d dose in 5q- syndrome patients. Although the achievement of transfusion independence may appear delayed compared to the standard 10 mg/d schedule, the reduction of haematological toxicity may be an important aspect in this patient population. In addition, with respect to the more conventional dose reduction schedule of 5 mg/d, our scheme has the advantage of lowering the cost of treatment by 50% in a subset of patients in which cost-effectiveness of new generation drugs as compared to best supportive care is still controversial (Goss et al, 2006; Greemberg et al, 2008). Despite the limited series of patients treated and the short follow-up, we believe that the rate of response together with the reduced toxicity and the good economic impact of the adjusted dose, strongly suggest that this schedule should be explored in a larger cohort of patients with 5q- MDS.