Pilot study 13cis-retinoic acid + dexamethasone + alpha interferon as maintenance therapy following high-dose chemotherapy and autologous stem cell transplant for multiple myeloma

Interleukin 6 (IL-6) is a major growth factor for myeloma cells and retinoids have been shown to inhibit expression of the interleukin 6 receptor (IL-6R). We performed a pilot study to assess the efficacy and tolerability of 13cis retinoic acid (13cRA) and dexamethasone (Dex), when added to interferon α (IFNα) as maintenance therapy post autologous stem cell transplantation. Between 90 and 120 days post stem cell transplantation, 33 patients were started on 13cRA 1 mg/kg p.o. daily for 14 days and Dex 40 mg p.o daily for 5 days every month. 13cRA was dose escalated by 0.5mg/kg/month to 2mg/kg. Seventeen patients had a persistent paraprotein post transplant. Overall, a response to therapy was observed in 11/17 (64%), with a complete response in 4/17 (23.5%) and a partial response (≥50% paraprotein decline) in 7/17 (41%). With a median follow-up of 34.8 months, 22/33 (66%) demonstrated disease progression and 11/33 (33%) died. The median progression-free survival from diagnosis was 34.7 months. Although a decline in paraprotein was frequently observed on triple therapy, many patients discontinued therapy due to the side-effects of the IFNα. Future trials should be designed using 13cRA and Dex alone.