A 58-year-old woman from Mumbai with newly diagnosed multiple myeloma (IgG-kappa type, 40% bone marrow plasma cells) undergoes staging investigations. Serum beta-2 microglobulin is 5.8 mg/L, serum albumin is 2.2 g/dL, and hemoglobin is 7.8 g/dL. Skeletal survey shows multiple lytic lesions in the spine and pelvis. She is started on bortezomib-based induction therapy. Which of the following complications is she at HIGHEST risk of developing during the first week of treatment?

Explanation

## Acute Complications of Myeloma Induction Therapy **Key Point:** Bortezomib-based induction therapy causes rapid tumor cell death, releasing intracellular contents (potassium, phosphate, uric acid, light chains) into the bloodstream—precipitating tumor lysis syndrome (TLS) within hours to days. ### Tumor Lysis Syndrome Risk Assessment **High-Yield:** This patient has MULTIPLE high-risk features for TLS: | Risk Factor | Patient Finding | Impact | |-------------|-----------------|--------| | Disease burden | 40% BM plasma cells + lytic lesions | Very high | | Renal function | Baseline Cr likely elevated (lytic disease) | Impaired urate clearance | | LDH status | Not stated but likely elevated | Indicates high cell turnover | | Therapy type | Bortezomib (proteasome inhibitor) | Rapid apoptosis | | Timing | First week of induction | Peak cell death phase | **Clinical Pearl:** Unlike lymphomas, myeloma TLS is often underappreciated because myeloma cells grow slowly in vivo. However, bortezomib induces rapid apoptosis, and the high tumor burden here makes TLS a real threat within 24–72 hours of starting therapy. ### Pathophysiology of TLS in Myeloma ```mermaid flowchart TD A[Bortezomib administered]:::action --> B[Proteasome inhibition]:::outcome B --> C[Plasma cell apoptosis]:::outcome C --> D[Release of intracellular contents]:::outcome D --> E[Hyperkalemia]:::urgent D --> F[Hyperphosphatemia]:::urgent D --> G[Hyperuricemia]:::urgent D --> H[Light chain release]:::urgent E --> I[Cardiac arrhythmias]:::urgent F --> J[Secondary hypocalcemia]:::urgent G --> K[Acute uric acid nephropathy]:::urgent H --> K K --> L[Acute kidney injury]:::urgent ``` **Mnemonic: TLS complications — HYPE** — **H**yperkalemia, **Y**uric acid nephropathy, **P**hosphate-induced hypocalcemia, **E**lectrolyte derangements ### Prevention and Management **Key Point:** Pre-treatment hydration, allopurinol/febuxostat, and rasburicase (urate oxidase) are essential before bortezomib in high-burden myeloma. ### Why Acute Kidney Injury Is the PRIMARY Acute Complication 1. **Uric acid precipitation** in renal tubules (hyperuricemia from cell lysis) 2. **Light chain cast nephropathy** (myeloma kidney from released kappa chains) 3. **Hyperphosphatemia** causing secondary hypocalcemia and metastatic calcification 4. **Hyperkalemia** causing cardiac toxicity (secondary to AKI) All of these converge to cause **acute kidney injury within 24–72 hours**, which is the most common and life-threatening acute complication of myeloma induction therapy.