Intracranial Myeloma treated with PACMED

Case prepared by Rashid Khan, MD;  Radiological images provided by Marcus Kessler, MD

We present here a 55 year old male patient with IgA Lambda multiple myeloma, diagnosed in 2007 when he presented with bone pain, from a para-spinal lumbar mass. He was treated at a local facility with initial XRT, then induction anti-MM therapy with Velcade, Revlimid and Dexamethasone, prior to referral to the Myeloma Institute in 2008 for stem cell collection. Given disease remission at that time, he collected 22 million CD34 cells/kg without autologous transplant, and was subsequently re-initiated and followed on Velcade-based maintenance locally, with disease stability for the next 4 years.

He suffered a fulminant relapse in August 2013, with 220+ focal lesions on PET-CT, 95% bone marrow involvement with Bartl grade III plasma cells (high-grade), and biopsy-proven extra-medullary disease (EMD) in his liver, with proliferation index of 100% (Ki-67 protein). He received salvage VD-PACE induction, followed by high-dose chemotherapy with melphalan 80, CDT-ACE and auto-HPC 4 with million CD34 positive cells per kilogram in September, 2013. He manifested a good anti-MM response to transplant, with 20% Bartl grade I-II bone marrow residual plasmacytosis, resolution of all active focal lesions on PET-CT and liver EMD. Subsequently, he was initiated on Carfilzomib and dexamethasone maintenance, with plans for a second autologous stem cell transplant upon his return in early 2014.

In January 2014, he presented to an outside hospital with symptoms of nausea, persistent headache and gait ataxia. CT brain revealed multiple small brain lesions, the largest in the posterior left parietal lobe which measuring 18×14 mm with associated edema. He was started on steroids, and transferred to the Myeloma Institute for further management.

 A staging PET-CT here showed 39 focal lesions with extensive EMD, manifested by numerous lesions in the brain, cerebellum, peduncle and spinal cord, and lymphadenopathy on both sides of the diaphragm. A fine needle aspiration biopsy of a neck lymph node confirmed a myeloma relapse, with CSF cytology also positive for malignancy. The patient was treated on an emergent basis with combination chemotherapy, comprising of high dose Cytarabine, Cyclophosphamide, etoposide, Cisplatin, Velcade and dexamethasone (PACMED-V), followed by a stem cell infusion. This produced a remarkable early anti-tumor response (see figures), which was consolidated with intra-thecal (IT) chemotherapy administered via an Ommaya reservoir and another round of systemic, dose-reduced PACMED, followed by HPC support. We saw a further reduction in disease mass with continued therapy, with reduction in focal lesion number and metabolic activity, bone marrow negativity by morphology and eradication of the patient’s CSF from malignant cells, by cytology and flow cytometry.