Pharmacy Services

M E M O R A N D U M

DATE: January 14, 2015

TO: ______________

FROM: Max Whitney, PharmD, Pharmacy Resident

SUBJECT: Management of meningeal myeloma

Even with conventional therapies, meningeal involvement of myeloma is a lethal condition with an overall survival of 4 to 6 months. The majority of information available for treatment of meningeal myeloma is embedded within retrospective analyses, and very few controlled trials exist to date. Although optimal treatment of meningeal myeloma is not clear, three treatment modalities consistently recur in literature to form the foundation for disease management: intrathecal (IT) chemotherapy, radiation, and systemic chemotherapy.

Intrathecal Chemotherapy

Intrathecal chemotherapy regimens in management of meningeal myeloma have become a preferred method for treatment due to effective and efficient eradication of disease in the CSF. The only uncertainty observed across studies is the frequency and/or duration of intrathecal therapy; however, all studies ultimately treated to the point at which the CSF was clear of disease.1-4 A retrospective study examining treatment of meningeal myeloma in 37 patients found that the sole therapy associated with improved overall survival was multi-dose (> 3 doses) intrathecal chemotherapy with cytarabine, methotrexate, and a steroid.2

A consolidated template of intrathecal chemotherapy for treatment of meningeal myeloma based on available literature follows.1-4

Template for Intrathecal Chemotherapy in Meningeal MyelomaAgent Dose Frequency Duration

Cytarabine 30 mg/m2

Every 4 to 7 days

Until normalization of

CSFMethotrexate 12 mgDexamethasone 4 mg

Of note, the package inserts of the above agents for the intrathecal treatment of meningeal leukemia state to administer an additional round of doses after confirmed normalization of CSF. In addition, common practice in patients with Omaya reservoirs is to administer only 6 mg of methotrexate.

Radiation

Radiation is a common denominator across all studies due the known radiosensitivity of plasma cell disorders. A statistically significant improvement in survival of 3 months versus 0.81 months in a review of 109 patients has been observed; however, the clinical significance of this improvement is questioned.5 In the study of 37 patients mentioned above, nine patients survived over one year. In these nine patients, all had received adjuvant radiation for their disease.2 Thus, radiation should still be strongly considered for incorporation into the management plan of meningeal myeloma patients.

Systemic Chemotherapy

Intrathecal administration with cytarabine, methotrexate, and dexamethasone is preferred over intravenous administration due to their effective and efficient normalization of the CSF, high CSF concentration, and fewer side effects. Systemic chemotherapy still maintains a role in the treatment of meningeal myeloma. Studies have found the combination regimen D(T)PACE (dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) to be effective in aggressive or refractory multiple myeloma.2,4

References

1. Yellu MR, Engel JM, Ghose A, Onitilo AA. Overview of recent trends in diagnosis and management of leptomeningeal multiple myeloma. Hematol Oncol 2014. Doi:10.1002/hon.2185

2. Chen CI, Misih-Khan E, Jiang H, et al. Central nervous system involvement with multiple myeloma: long term survival can be achieved with radiation, intrathecal chemotherapy, and immunomodulatory agents. Br J Haematol 2013;162(4):483-488

3. Grisold A, Weber C, Hainfellner J, et al. MRI negative meningeal myeloma with abducens nerve palsies responding to intrathecal chemotherapy. J Neurol Sci 2014;347(1-2):359-360

4. Gerrie AS, Mikhael JR, Cheng L, et al. D(T)PACE as salvage therapy for aggressive or refractory multiple myeloma. Br J Haematol 2013;161(6):802-810

5. Nieuwenhuizen L, Biesma DH. Central nervous system myelomatosis: review of the literature. Eur J Hematol 2008;80:1–9