Histamine dihydrochloride, interleukin-2 and interferon-alpha in multiple myeloma

Histamine has been reported to enhance immunoactivation induced by interleu kin (IL)-2 and interferon (IFN)-alpha in vitro, and combination therapy wit h histamine dihydrochloride and IL-2 has been used in malignant melanoma an d acute myelogenous leukemia. A pilot study was conducted with the primary aim of monitoring the safety and feasibility of histamine and low-dose IL-2 in patients with multiple myeloma. Six patients, median age 53 years (rang e 45-62), were enrolled 17 months (10-64) after autologous stem cell transp lantation. IL-2 (0.9 MIU a. c. b.i.d.) was given in repeated 21-day cycles. Histamine dihydrochloride (0.5 mg s.c. b.i.d.) was given together with IL- 2 from the second cycle. Treatment was continued until disease progression or for 6 months; patients in the first responsive phase also received IFN-a lpha 9 MIU/week. IL-2 induced fever; aches, fatigue and inflammation at inj ection sites. Histamine induced short lasting symptoms due to vasodilatatio n (headache, flush, mild hypotension and tachycardia). The number of circul ating eosinophils, basophils and natural killer cells increased during trea tment. After a median follow-up of 39 months (17-47), two out of four patie nts in responsive phase have maintained their status, one has relapsed and one has improved. Two patients in progressive phase have continued to progr ess. We conclude that histamine, given as an adjunct to immunotherapy in my eloma patients after autologous stem cell transplantation, is safe and feas ible.