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?

Question

Accepted Answer

A. Tumor lysis syndrome with acute kidney injury. ## 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.

Answer

B. Secondary amyloidosis

Answer

C. Peripheral neuropathy

Answer

D. Hyperviscosity syndrome

Explanation

Acute Complications of Myeloma Induction Therapy

Tumor Lysis Syndrome Risk Assessment

Pathophysiology of TLS in Myeloma

Prevention and Management

Why Acute Kidney Injury Is the PRIMARY Acute Complication

Practice similar questions

Join our NEET PG community

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