Case study | Relapsed MM with intracranial plasmacytoma and malignant pericardial effusion post-transplant

Here we present an unusual case of an aggressive relapse of Multiple Myeloma (MM), with both central nervous system (CNS) and pericardial involvement, appearing within 4 months’ post-transplant. This case was documented in Case Reports in Oncology in July 2017 by Jonathan Pan and colleagues from the Department of Medical Oncology, Thomas Jefferson Hospital, Philadelphia, PA, USA.

Key Highlights:

• Female patient (pt) aged 54; a history of IgG kappa MM diagnosed following presentation with pain in shoulders and ribs
• Serum protein electrophoresis (SPEP) showed an M-spike with monoclonal IgG kappa concentration = 3.5 gm/dL, total serum IgG = 5,805 mg/dL, β₂ microglobulin = 2.3 mg/L, albumin = 3.9 g/dL, LDH = 272 IU/L
• International Staging System (ISS) = stage I; translocation (4; 14), trisomy 9, and monosomy 13
• Treated with 1 cycle of lenalidomide/dexamethasone followed by radiation of the jaw, spine, and right cavernous sinus, then 4 cycles of lenalidomide, bortezomib, and dexamethasone
• Due to increased bone disease in her ribs, femur, and hip, she received 3 cycles of carfilzomib, lenalidomide and dexamethasone, as well as further radiation therapy directed to these regions
• Follow-up biochemical analyses indicated a return to normal and bone marrow (BM) biopsy < 1% clonal plasma cells
• A reduced-intensity allogeneic HSCT was carried out, using a fludarabine, busulfan, and cyclophosphamide conditioning regimen; no intracranial pathology identified by CT scan
• A plasmacytoma of the thoracic spine was then identified 2 months post-HSCT, and was treated with additional radiation therapy with good response; BM biopsy showed complete donor engraftment and was negative for abnormal cells; SPEP = IgG kappa level of 0.2 gm/dL
• A spinal MRI at 3 months post-HSCT revealed new thoracic soft tissue lesions, and a brain MRI revealed a new extra-axial right occipital lobe mass extending to the cerebellum
• The patient underwent right craniotomy with partial resection of the brain lesion; pathology revealed CD138-positive cells characteristic of plasmablastic plasmacytoma
• Cranial and spinal irradiation improved her condition, but during this time a large pericardial effusion was observed on a CT thorax; fluid analysis of the cardiac tamponade revealed CD138-positive plasma cells
• At this stage, the patient was kept comfortable with hospice care and died 1 month later

This is an unusual presentation of extremely rapidly progressing MM. BM biopsy and SPEP results indicated minimal disease burden immediately after HSCT. The authors could not find any similar cases previously reported in the literature, suggesting that such rapid CNS involvement is extremely rare. In general, CNS involvement occurs in relapsed patients predominantly as leptomeningeal disease. However, alterations of chromosome 13 and 17, and translocation 4;14 have been associated with a higher risk of extramedullary myeloma, as well as elevated lactate dehydrogenase (LDH) levels and IgA or IgD myeloma subtypes. In this case the patient had an IgG subtype, but raised LDH, chromosome 13 deletion and translocation 4;14. Histological examination of the plasmacytoma also displayed Ki-67 positivity, which has been linked to extraosseous relapse of MM. However, cardiac involvement was unusual and unexpected.

This rare case highlights the need to carefully monitor relapse and to be mindful of high-risk indicators. With a trend towards precision medicine and tailored regimens, clearer genetic and biochemical indicators are emerging that will enable more effective stratification of risk and prognosis, and are likely to be incorporated into early diagnostic work-ups.