Myelomatous Pleural Effusion of Multiple Myeloma: Characteristics and Outcome.

Myelomatous pleural effusion (MPE) in multiple myeloma (MM) is rare (<1%). As most reported MPEs are in the form of case reports, the characteristics of MPE are unclear. We report 30 MM patients presenting with MPE, including 11 cases as the first clinical manifestation of MM. To the best of our knowledge, this is the largest retrospective study ever reported about MPE.

Multicenter retrospective data of MM patients presenting MPE, who were diagnosed from January 1998 to June 2009 were analyzed. Diagnosis of MPE was based on positive cytology or biopsy in conjunction with M protein by protein electrophoresis or immunofixation in pleural effusion.

The median age was 53 (range 21-78). Twenty patients were male and 10 were female. The myeloma isotype was IgG in 8, IgA in 7, IgD in 5, light chain in 9 and non-secretory myeloma in 1 patient. Most patients had high-risk disease based on initial D-S stage IIIA or IIIB (83%). Thirteen of 19 patients, who had available BM chromosomal analysis or FISH result, showed various karyotypic abnormalities including deletion of chromosome-13 (n=8). MPE was the first manifestation of MM in 11 patients (early-onset group). In the other 19 patients (late-onset group), MPE developed at a median of 20 months (range 1 – 75) from diagnosis of MM. The effusions were left-sided in 6, right-sided in 9 and bilateral in 15 patients. In more than half of the cases, a thoracic skeletal lesion, lung parenchymal lesion, pleural involvement or mediastinal lymphadenopathy was concomitantly present. Before the development of MPE, median 2 lines of chemotherapy (range 1 – 9) were applied in late-onset group. Seven patients of this group received high-dose chemotherapy with stem cell transplantation (6 autologous and 1 allogeneic stem cell). After onset of MPE, the median number of chemo-regimen was 1 (range 0 -3) in both groups and 3 patients got high-dose chemotherapy with autologous stem cell transplantation (1 in early-onset and 2 in late-onset group). After onset of MPE, total 27 chemo-regimens were applied to 19 patients and the regimens were based on VAD (vincristine, adriamycin, dexamethasone) in 12, thalidomide in 5, bortezomib in 4 and other regimen in 6. Pleurodesis was done in 2 patients. MPE disappeared in 11 patients and median response duration, defined as days from disappearance to relapse of MPE or death of any cause, was 123 days (95% confidence interval (CI): 10 – 236). Median survival was 66 days (95% CI: 29 – 103) from onset of MPE and 16 months (95% CI: 5 – 28) from initial diagnosis of MM. From onset of MPE, median survival was 84 (95% CI: 57 – 111) and 55 days (95% CI: 0 – 113, p=1.0) in early and late-onset group, respectively. From initial diagnosis of MM, median overall survival was 2.8 (95% CI: 2.4 – 3.2) and 26 months (95% CI: 12 – 40, p<0.001) in early and late-onset group, respectively. Causes of death were progression of disease, progression with concomitant infection or infection (50, 23 and 8 %, respectively).

Base on this analysis, MPE is a poor prognostic indicator, irrespective of the time of onset. When pleural effusions develop in a patient with MM, clinicians should perform prompt and appropriate diagnostic work-up. In the case of MPE, aggressive treatment including novel agents or autologous stem cell transplantation should be considered, especially if MPE is the initially presenting manifestation of MM. Further evaluation of the utility of various novel chemotherapeutic agents in the setting of MPE is needed to improve treatment outcome.

No relevant conflicts of interest to declare.