Use of Immunoglobulin Infusions in the Management of Bortezomib-Induced Peripheral Neuropathy in Multiple Myeloma.

Bortezomib (VELCADE) is a novel proteasome inhibitor that has shown tremendous clinical efficacy in Asian patients with multiple myeloma (MM). Prior studies have found that about a third (35%) of Caucasian patients develop bortezomib-induced peripheral neuropathy (PNY); and 12% and 5% of these patients require dose-reduction or discontinuation of bortezomib, respectively. Moreover, it has anecdotally been reported that a greater proportion of Asian patients receiving bortezomib develop PNY, and we are concerned that this unwanted effect of bortezomib would greatly limit the use of a drug that would otherwise be highly-effective for Asian MM patients. We therefore analyzed 20 Asian patients with MM who were treated with bortezomib, and found that up to 75% (15 out of 20) of patients developed bortezomib-induced PNY - sensory (75%) and/or motor (50%); confirming the observation that Asian patients are more prone to developing bortezomib-induced PNY. The majority of sensory PNY were mild. Grades 1 or 2 sensory PNY was seen in 45%, grade 3 in 15%, and grade 4 in another 15% of patients. Of these, 80% of patients reported painful neuropathies - 53% requiring dose reduction, and 27% requiring discontinuation of bortezomib. By contrast, motor PNY was more severe - 5% of patients reported grades 1 or 2, 15% with grade 3, and 30% with grade 4 motor PNY. In other words, if PNY develops in an Asian patient with MM, it is more likely to be a mild painful sensory PNY. However, if motor PNY occurs, it is more likely to be severe. For the treatment of PNY, all patients received gabapentin (600 mg to 1,400 mg per day), and 9 patients received L-carnitine (2 or 3 tablets a day). Gabapentin-treated patients reported only minimal effectiveness of this drug in relieving their symptoms, whereas no objective improvements were observed in all L-carnitine-treated patients. Similarly, amitriptyline was given to 3 patients with severe painful PNY and only a non-sustained modest improvement was reported in all these patients. In contrast, improvements of at least 1 grade in both symptoms and function were reported by all 9 patients who received intravenous immunoglobulins (IVIG). In the most significant of these, a patient who was bed-ridden because of grade 4 combined sensorimortor PNY, dramatically recovered (became pain-free, and improved to grade 2 motor weakness) within 2 days of completing IVIG 2.0 gm/kg divided over 4 days. In conclusion, Asian MM patients have indeed significantly higher rates of bortezomib-induced PNY, which unfortunately often leads to dose-reduction and/or discontinuation of bortezomib. Our data demonstrate that IVIG may be a useful agent for the management of these patients; and for facilitating the continued administration of bortezomib.