Thalidomide in Haematology Practice at an UK District General Hospital - A 6 Year Experience.

Introduction-This is a retrospective audit of thalidomide use in haematology practice at a district general hospital in UK over past 6 years from 2000 to June 2006. Thalidomide is not yet licensed in the UK.

Audit summary-Thalidomide was administered to 44 patients (31 males 13 females). The median age range was −71–80 years (n=19). None of the 13 females had childbearing potential. Only one patient was enrolled in a clinical trial - Myeloma IX. Thalidomide usage ranged from 4–682 days (multiple myeloma),2–443 days (non – Hodgkin’s lymphoma),72–856 days (myeloproliferative disorder/myelofibrosis), 21–134 days (myelodysplastic syndrome) & 2239 days in a patient with oral ulceration secondary to Behcets disease. Thalidomide was administered alone (n=12), in combination chemotherapy (22) [Thalidomide/Dexamethasone 6, Thalidomide/Prednisolone 2, attenuated Cyclophosphamide/Thalidomide/Dexamethasone (CTD) 3 & CTD 11] & both (10). Minimum & maximum tolerated dose was 50 mg alternate day & 300 mg od, respectively. 20 patients needed dose reductions.

Multiple Myeloma (n=20) First line of treatment in one patient (survival post initiation 16 months +), second line 5 patients (6days to 38 months), third line 5 patients (15 days to 19 months), fourth line 6 (6months to 19 months+), fifth line 2 patients (1 ½ months to 4 ½ months) & sixth line 1 patient(66 months+). Outcome-loss of response (n=15), good response/minimal residual disease (3), partial response (1) & side effects (14).13 patients died.

Non Hodgkin’s Lymphoma (n=13) Second line of treatment in one patient (survival post initiation 2 days), third line 4 (20 days to 14 months +), fourth line 4 (13 days to 31 months +), fifth line 1 (7 ½ months) & eighth line 2 (9 days to 4 months). Outcome-side effects (8), stable disease (1) & progressive disease (9). 10 patients died.

Myeloproliferative disorder/Myelofibrosis (n=6) First line of treatment in one patient (survival post initiation 14months+), second line 2 (12 to 17 months+), third line 2 (26 months to 31 months) & fourth line 1 (10 months). Outcome - loss of response (4), no response (1) & side effects (6). 4 patients died.

Myelodysplastic syndrome (n= 4) Second line of treatment in 1 patient (survival post initiation 53 months +), third line 2 (11 to 27 months), fourth line 1 (13 months). Outcome-no response (1), disease progression (1) & side effects (3). 3 patients died.

Oral ulceration secondary to Behcets disease later complicated by myelodysplasia (n=1) First line treatment. Outcome-loss of response (survival post initiation 74 months).

Side-effects (31 of 44 patients)-Paresthesia n=13, somnolence 6, tiredness 6, constipation 6, neutropenia5, giddiness 4, unsteady gait 3, bodyache 3, deep vein thrombosis 3, tremors 3, nausea 2, , anorexia 2, visual blurring 2, dry skin 2, sepsis 2, unconfirmed pulmonary embolism 1 & other 11.16 patients discontinued thalidomide. There were 4 venous thromboembolic episodes (3 DVT, 1 unconfirmed pulmonary embolism) in 3 patients.

Conclusion- Analysis of thalidomide usage offers a better understanding of it’s utility by identifying practice, outcome & safety concerns.