IgM Multiple Myeloma in Afro-Caribbean Patients: A Report of Two Cases

Introduction/Background/Significance: IgM multiple myeloma (MM) is a rare plasma cell malignancy representing less than 0.5% of all MM cases. It presents a unique diagnostic challenge due to its clinical and biochemical overlap with Waldenström macroglobulinemia (WM). Accurate diagnosis is essential for guiding appropriate treatment. Notably, more studies have found racial variations in MM. Individuals of African descent are reported with the highest incidence worldwide in MM, yet data on IgM MM in this population are very limited.

Materials and Methods/Case Presentation/Objective: We presented two cases of IgM MM in Afro-Caribbean patients aims to describe the clinical, radiologic, molecular, and cytogenetic characteristics of IgM MM in this population and highlight the diagnostic approach distinguishing it from WM.

Results/Description/Main Outcome Measures: Patient 1

A 74-year-old male Guyanese patient with history of end-stage renal disease, presented with severe anemia and recurrent gastrointestinal bleeding. Endoscopy showed hemorrhagic gastritis. Workup revealed hemoglobin of 4.3 g/dL, corrected serum calcium elevated at 13.9 mg/dL, SPEP revealed an M-protein spike of 4.1 g/dL, immunofixation identified an IgM-kappa monoclonal band, IgM 5548 mg/dL, kappa/lambda ratio of 2.8, osteolytic skull lesions on CT head, and 80-90% plasma cell involvement with no lymphoplasmacytic infiltrate in bone marrow. FISH testing identified a CCND1-IGH translocation [t(11;14)], and next-generation sequencing (NGS) revealed pathogenic mutations in IKZF1 and FAM46C, and no MYD88 mutation. Hospital course was complicated by suspected hyperviscosity syndrome given neurologic symptoms of confusion, increased bleeding tendency, and serum viscosity elevated at 3.8 cP (centipoise serum viscosity). Patient was started on bortezomib-based therapy with plasmapheresis. Despite initial management, he experienced sudden cardiac arrest and passed away during hospitalization.

Patient 2

A 65-year-old male of Caribbean descent presented with progressive lower back pain and acute kidney injury. The workup revealed hemoglobin of 5.6 g/dL, creatinine of 4.6 mg/dL, SPEP revealed an M-protein spike of 4.5 g/dL, immunofixation identified an IgM-kappa monoclonal band, IgM 6290 mg/dL, kappa/lambda ratio of 480.76. Imaging revealed lumbar compression fractures, bone islands without classic lytic lesions. Bone marrow biopsy showed >90% plasma cells with no lymphoplasmacytic infiltrate. FISH testing was positive for a t(11;14) gene rearrangement, a 13q deletion, a 1q gain, and no MYD88 mutation on NGS. The patient received dexamethasone 40 mg daily for 4 days, resulting in improvement in creatinine from 5.6 to 1.88. A treatment plan of Dara-RVD with renal-dose lenalidomide for 4 cycles was initiated. The patient continued regular follow-up in the myeloma clinic.

Conclusions: We reported two cases of IgM multiple myeloma in Afro-Caribbean patients, illustrating the variability in clinical features and outcomes seen with this rare disease. In both cases, a thorough workup—including clinical assessment, imaging, pathology, molecular studies, and cytogenetics—was essential to making the correct diagnosis. The identification of t(11;14) and the absence of MYD88 mutations were key in distinguishing IgM myeloma from Waldenström's macroglobulinemia. As IgM myeloma remains poorly characterized in the literature, further studies are needed to refine diagnostic criteria and better understand its clinical significance.