Urine electrophoresis for Bence Jones protein is the best initial investigation.

The combination of anemia, leukopenia, bone/back pain, weight loss, renal impairment, and likely marrow involvement strongly suggests multiple myeloma. Urinary light chains (Bence Jones proteins) support the diagnosis. Bence Jones proteinuria occurs in roughly 50% to 80% of multiple-myeloma cases (Henry's Clinical Diagnosis and Management by Laboratory Methods). Current diagnostic work-up also includes serum protein electrophoresis, serum free light chains, calcium/creatinine, and bone-marrow testing, as summarized in the IMWG diagnostic criteria.