Thalidomide Effects in the Post-transplantation Setting in Patients with Multiple Myeloma

Abstract

Thalidomide recently has been proven to have an impact on plasma cell dyscrasia through multiple mechanisms. Its effects on hematopoietic stem cells both in harvesting and in the immediate post-transplant setting are still unknown. We report on 12 cases (9 males and 3 females), median age 56 years old (range 41-65 years old) who underwent autologous peripheral stem cell transplantation for multiple myeloma and received thalidomide as maintenance therapy post-transplantation. Patients received various cytoreductive therapies prior to stem cell harvest. Eleven patients were in partial remission (PR) and one in complete remission (CR) on entry into the transplant phase of therapy. The median CD34<PRE>+</PRE>/kg harvested was 4.7×10<PRE>6</PRE> (range 1.9-55.4×10<PRE>6</PRE> CD34<PRE>+</PRE>/kg). All patients received intravenous melphalan 200 mg/m<PRE>2</PRE> as their conditioning regimen. Six of twelve patients attained a CR post-transplant, and six a PR. Thalidomide was started after all patients engrafted post-transplant (absolute neutrophil count >0.5×10<PRE>9</PRE>/l and self-sustained platelet count >20×10<PRE>9</PRE>/l) and following satisfactory resolution of transplant toxicity including mucositis and diarrhea. Thalidomide was initiated at a median of 43 days post-transplant (range 23-138 days). The median leukocyte and platelet counts at the moment of thalidomide initiation were 5.8×10<PRE>9</PRE>/l (range 2.9-8.6×10<PRE>9</PRE>/l) and 196×10<PRE>9</PRE>/l (range 30-351×10<PRE>9</PRE>/l), respectively. Thalidomide was started at 100 mg daily, increasing 100 mg/day/month until reaching a dose of 400 mg/day. One patient failed to tolerate thalidomide due to CNS symptoms and stopped therapy at 12 days. Another patient stopped thalidomide therapy after 71 days, because of severe fatigue secondary to hypothyroidism. The most common adverse effects were constipation (5), rash (4), dry skin (3) and dizziness (3). No grade 3-4 adverse effects were documented. Neutropenia, previously reported as an adverse effect in this setting, was not seen to date in our cohort. All patients attained a CR or PR after transplant and thalidomide maintenance. We have had two relapses during a median follow-up of 68 weeks (range 42-172 weeks).

Conclusion: Thalidomide appears to be a safe drug in the post-transplant setting, perhaps adding to the response achieved post-transplant without major toxicity. Longer follow up and future randomized trials will be needed to validate the role of thalidomide and its long-term effect when used as maintenance therapy in the post-transplant setting.

Keywords:

• Thalidomide
• Post-transplantation
• Multiple myeloma
• Side effects