Evaluation of Bortezomib-Induced Neuropathy Using Total Neuropathy Score (Reduced and Clinical Versions) and NCI CTCAE v4.0 in Newly Diagnosed Patients With Multiple Myeloma Receiving Bortezomib-Based Induction

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Abstract

Background:

Bortezomib-induced peripheral neuropathy (BiPN) is a dose-limiting adverse effect of bortezomib-based therapy for multiple myeloma (MM). The reporting of BiPN is variable because of the use of different neuropathy scales. Most investigators use the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).

Patients and Methods:

We prospectively evaluated the incidence of BiPN in treatment-naive patients with MM receiving weekly cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in 28-day cycles using 3 neuropathy scores: Total Neuropathy Score—reduced (TNSr) and —clinical (TNSc), and NCI CTCAE v4.0.

Results:

Twenty-six patients received CyBorD. Twenty patients completed follow-up. The rates of occurrence of BiPN were as follows: TNSr - 55% (n = 11), TNSc - 40% (n = 8), and NCI CTCAE - 45% (n = 9). All 3 scales showed worsening after treatment (P < .01). When compared to BiPN by TNSr, sensitivities for NCI CTCAE and TNSc were 77.8% and 88.9%, respectively. Specificity was 63.3% for both NCI CTCAE and TNSc. Among 12 patients who did not have BiPN by NCI CTCAE scale, 41.7% (n = 5) and 16.7% (n = 2) patients satisfied the criteria for BiPN by TNSr and TNSc, respectively. The higher detection rate of neuropathy by TNSr and TNSc is probably due to increment in scores that are allotted for increase in anatomic extent of sensorimotor involvement, unlike the NCI CTCAE scale, which requires functional limitation for increase in grade.

Conclusion:

NCI CTCAE may be suboptimal in comparison to TNSr and TNSc in assessment of BiPN because it may miss worsening neuropathy without functional limitation.

The Total Neuropathy Score is ideal for evaluation of bortezomib-induced neuropathy. We used the reduced (TNSr) and clinical (TNSc) forms as well as the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 to assess incidence of neuropathy in patients receiving cyclophosphamide, bortezomib, and dexamethasone as induction for multiple myeloma. Out of 20 evaluable patients, 55%, 40%, and 45% developed neuropathy when assessed by TNSr, TNSc, and NCI CTCAE, respectively. We found wide variation in TNSr and TNSc even when the NCI CTCAE scale reported no progression of neuropathy.

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