Treatment of Menigeal Myelomatosis with Liposomal Cytarabine (DepoCyte®): A Case Report

Abstract

Involvement of the central nervous system (CNS) in multiple myeloma (MM) is very uncommon. The incidence has been described to be approximately 1% of MM patients. The diagnosis is difficult because CNS MM presents with a wide spectrum of subtle neurological signs and symptoms which may result in some underdiagosis of this complication. The diagnosis is usually based on neurological symptoms and the detection of plasma cells in the CSF. An earlier diagnosis may be achievable by using immunoelectrophoresis and immunofixation for detection of monoclonal protein or the use of flow cytometry and cytogenetic analysis of CSF samples. No guidelines for therapy of CNS MM are available which has resulted in the use of a large variation in treatment schedules. Treatment options include intrathecal chemotherapy (IT), systemic chemotherapy (SC), cranial irradiation (CI) or a combination of these methods. A significant positive impact on overall survival (p=0.004) was recently reported for patients treated with CI when compared with patients without CI). However, even when a complete response in the CSF was achieved patients' often succumb to the aggressively progressing systemic disease. As a result the prognosis of CNS MM remains very poor with a median overall survival from the time of diagnosis of 2 months (range 0.1–25 months), despite all efforts to improve treatment. Although palliative by nature we believe that treatment of LMM is indicated, given its potential for symptomatic relief and improvement in the quality of life.We describe a case of a 54 year old female with multiple myeloma (stage III-A) involving the central nervous system and lungs. She was initially successfully treated in November 2005 with thalidomide and dexamethasone. In February 2007, the patient experienced bone pain and a re-evaluation of the disease showed 90% monoclonal plasma cells in the bone marrow. In April 2007 the patient received two cycles of DT-PACE (dexamethasone, thalidomide plus cisplatin, doxorubicin, cyclophosphamide, etoposide) but the CT scan showed a progression of extramedullary disease. Treatment was therefore changed in May 2007 and the patient received five cycles of PAD (bortezomib, doxorubicin and dexamethasone) plus RT on D9 and D11. A total body CT scan performed in November 2007 revealed progressive disease at para-vertebral sites D3, D4 D5, D8 and D9. The liver was hypodense with nodular lesions and multiple para-ovarian lesions were detected. The patient received Melpahan 200mg/m2 with reinfusion of autologous stem cells. A total body CT scan in January 2008 showed an unchanged abdominal situation and many myelomatosis infiltrations in lumbar and dorsal side of the lung. The patient was then admitted to our hospital in March 2008 now with headache and diplopia. Whilst the MRI and CT scan did not reveal evidence of CNS involvement the CSF flow cytometry analysis showed 40% plasma cells and confirmed the diagnosis of leptomenigeal myelomatosis. The patient received four doses DepoCyte® every two weeks and bendamustine 100mg/m2 day 1,2; bortezomib 1.3mg/m2 day 1,4,8,11 and prednisolone 100mg day 1,2,4,6,11 every 21 days. Flow cytometry and cytospin analysis of the CSF were performed at every LP. The headache and diplopia rapidly disappeared and the CSF was clear from plasma cells after the second DepoCyte® injection. Because of progressive systemic disease the patient refused further treatment in May 2008 and died in June 2008.Conclusions: CNS involvement in MM is rare and a late complication in the course of the disease. The prognosis of such patients is poor based on often refractory systemic disease despite aggressive systemic and local treatment. A better understanding of the biology of LMM and an early identification of patients with high-risk for CNS myeloma involvement may allow earlier treatment with better results. Liposomal cytarabine was effective and well tolerated; no drug-related side effects or haematological toxicity were recorded.