Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence.
Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM.



A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse.



CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement.



In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.
a Department of Haematology/Oncology , National University Cancer Institute Singapore (NCIS) , Singapore.
Muhammad Bilal
MB
Abid
a Department of Haematology/Oncology , National University Cancer Institute Singapore (NCIS) , Singapore.
Sanjay
S
De Mel
b Department of Otolaryngology - Head & Neck Surgery , Johns Hopkins University , Baltimore , MD , USA.
Muhammad Abbas
MA
Abid
c Department of Pathology , National University Hospital Singapore (NUHS) , Singapore.
Kong Bing
KB
Tan
a Department of Haematology/Oncology , National University Cancer Institute Singapore (NCIS) , Singapore.
Wee Joo
WJ
Chng
D000069286:Bortezomib / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D011379:Prognosis
D000069286:Bortezomib
Autologous stem cell transplantation (ASCT); bortezomib (velcade); bortezomib-induced peripheral neuropathy (BIPN); immunomodulator (IMID); multiple myeloma (MM); proteasome inhibitors (PI)