P-466: PERIPHERAL AND SEVERE AUTONOMIC NEUROPATHY CHARACTERIZED BY DIZZINESS, ORTHOSTATIC HYPOTENSION AND WEIGHT LOSS CAUSED BY BORTEZOMIB.

Introduction: Bortezomib (B), used to treat Multiple Myeloma (MM) causes peripheral neuropathy (PN) in an estimated 75% of patients. There are reports of dizziness, muscle weakness and other neurologic problems caused by B. Among patients that received B based induction, in addition to PN, in a small subset we observed profound weight loss, dizziness and orthostatic hypotension (OH). These symptoms frequently impair patients’ performance status requiring interruption of therapy. There are few publications on autonomic neuropathy (AN) caused by B but we believe it is under recognized and under diagnosed. We report a series of patients that presented with significant weight loss and OH suggestive of AN, to bring awareness to this problem.

Methods: From July 2017 to July 2022, patients with MM requiring transplant; complaining of weight loss and dizziness were identified. Medical records were reviewed and a pattern of symptoms and clinical course were identified. Statistics are descriptive and this retrospective study was approved by our Institutional review board.

Results: Fourteen patients were noted to have symptoms suggestive of AN. 12 received VRD and 2 received (Daratumumab) D-VRD induction. B was given subcutaneously and twice weekly. The median age was 61 years (range 51-76). Nine were African American and 5 White; 5 female, 4 had diabetes but no prior neuropathy. The interval between initiation of therapy and AN symptoms was a median of 124 days (range 50-219) and the median B dose was 20.8 mg/M2 (range 11.7-40.33 mg/M2). All 14 patients had weight loss. The median weight loss and percentage weight loss (compared to baseline weight) were 19.5 Kgs (range 7-39.14 Kgs) and 21% (range 7-41) respectively. Further treatment was held due to decline in performance status in all patients. Eight patients received appetite stimulants; 2 megestrol and 6 dronabinol. OH was seen in all patients; 3 received fludrocortisone and one received midodrine. 12 patients also had PN requiring neuropathic pain medications and narcotic analgesics.
Transplant was delayed by 6 months (range 2-11) to enable recovery and the end-point was weight gain, and resolution of OH. 12 patients received transplant; Post-transplant 1 patient had persistent diarrhea and 1 had persistent dizziness. One patient developed severe mucositis, dysphagia, poor appetite and required hyper alimentation, nasogastric feeding and a feeding gastrostomy tube. With a follow up of 30.2 (range 8.47-53.6) months, the median survival is 30.82 months.

Conclusions: Severe AN characterized by weight loss, dizziness, OH in association with painful neuropathy is an under recognized complication of B. Transplantation without resolution of symptoms could possibly worsen the morbidity and delay post-transplant recovery. To the best of our knowledge, we are the first group to report a series of patients with this symptom complex and strongly feel it should be studied further in a larger cohort of patients.