Anaplastic Myeloma Arising from Myeloma: Successful Management of Two Diseases in an Individual

Introduction

Multiple myeloma is known to have progressive mutations that lead to a dominant aberrant plasma cell clone and a number of subclones. Mutations can lead to more aggressive forms of myeloma, but rarely does it transform into an immature variant such as anaplastic myeloma. This particular variant has a predisposition for extramedullary sites and is related to IgA plasma cell variants. Unlike standard myeloma that responds better to novel agents such as proteasome inhibitors and immunomodulators, this poorly differentiated cell is highly resistant to therapy and has very poor outcomes.

In the following case report, we present a patient with IgA kappa anaplastic myeloma that evolved from multiple myeloma. We will demonstrate how a combination of novel agents in conjunction with conventional chemotherapy was a successful therapy for both plasma cell variants.

Case Report

A 60 year-old man had a three month history of confusion, headaches, and leg weakness. He did not seek medical attention until he lost vision on his right eye. On exam, he had right ptosis with a dilated pupil fixed downward and laterally. MRI of the orbit showed a right orbital apex mass surrounding the optic nerve and diffuse leptomeningeal enhancement. A PET/CT, to better characterize the extent of disease showed right laryngeal, lung, and femoral hypermetabolic lesions in addition to the orbital mass. A biopsy of the laryngeal mass showed an IgG kappa anaplastic myeloma with Ki-67 of 70% and FISH positive for +12 and +14. Serology demonstrated an IgA M-spike of 1.56 with an abnormal serum free light chain ratio of 118.31. He underwent a bone marrow biopsy that showed 30% kappa-restricted plasma cells with 13q- and +11 by FISH and a lumbar puncture that demonstrated CNS involvement by CD38+ clonal plasma cells. He was classified as systemic stage I IgA kappa myeloma by R-ISS with localized anaplastic myeloma showing similar light chain restriction by immunohistochemistry.

The patient received HD methotrexate 3 g IV with evidence of leptomeningeal response but evidence of sytemic progression on eye mass within a week despite of stable myeloma serology. He received 4 Gy as a single dose to the eye mas that shrunk the tumor. HyperCVAD with IT cytarabine alternating with MTX was started with a significant improvement in plasmacytomas by PET scan after 2 cycles of therapy. Flow cytometry from CNS became negative at that time but paraprotein remained unchanged.

A bone marrow biopsy performed after the 4th cycle of chemotherapy showed 30% clonal plasma cells with stable M-spike at 1.45 and serum free light chain ratio of 79. Seeing that the CNS fluid was now negative and the orbital and leptomeningeal lesions had improved, therapy was changed to carfilzomib, pomalidomide, and dexamethasone but continued on IT chemotherapy alternating cytarabine and MTX. His M-spike resolved after 3 cycles of treatment. His immunofixation continued to detect IgA kappa clone and serum free light chain ratio dropped to 19.08.

Follow up

The patient continues tolerating treatment with no evidence of systemic or CNS relapse disease. He remains on carfilzomib, pomalidomide, and dexamethasone as maintenance for systemic therapy combined with monthly IT chemotherapy. He developed one episode of confusion thought to be from white matter changes from IT chemotherapy but those symptoms have resolved.

Discussion

This unique scenario of a patient having both myeloma and anaplastic myeloma poses a challenge in management. While novel agents may be good to control the myeloma, more primitive forms of myeloma cells do not have the epitopes these agents bind to in order to cause cell destruction. Since anaplastic myeloma is more aggressive, targeting it with conventional chemotherapy that penetrated the CNS barrier seemed like a good initial treatment until CNS disease control was achieved, with focus on the more indolent myeloma afterwards with novel agents. Out of those, we included one known to have CNS penetration (pomalidomide). This approach was effective in this case and could be applied in future cases as clinical trials on such rare disease wouldn't be feasible.

The similarities between the two plasma cell neoplasms shows the significant difference myeloma subclones can have. This proves the concept that myeloma does not behave as a single tumor, but more like clusters of different myeloma strains that can branch off the dominant clone and lead to relapse or refractory disease.