THE ADDITION OF CYCLOPHOSPHAMIDE TO LENALIDOMIDE AND DEXAMETHASONE IN MULTIPLY RELAPSED/RERACTORY MYELOMA PATIENTS; A PHASE I/II STUDY

Stephen Schey (1) , Gareth J Morgan (2) , Karthik Ramasamy (3, 4) , Beth Hazel (5) , Sophie Corderoy (5) , Dariusz Ladon (5) , Mathew Jenner (2) , Karen Phekoo (5) , Kevin David Boyd (6) , Faith E Davies (2)

1 Haematology
2 Section of Haemato-oncology
3 Haematological Medicine
4 King‘s College London
5 Haematology
6 Haemato-oncology

Two identical Phase III randomised trials confirmed significant clinical activity of lenalidomide and dexamethasone in relapsed myeloma. We report the results of a Phase I/II dose escalation study, set out to evaluate the optimal dose of cyclophosphamide when used in combination with a fixed dose of Lenalidomide and dexamethasone in relapsed/refractory myeloma. A total of 31 patients were enrolled in cohorts of 3 patients at 5 dose levels of cyclophosphamide to a maximum dose of 700mg days 1 and 8 of a 28 day cycle. Patients received Lenalidomide 25 mg days 1-21 and dexamethasone 20mg orally days 1-4 and 8-11. The maximum tolerated dose of this regimen is 600mg cyclophosphamide days 1 and 8 and the regimen is well tolerated with grade 3/4 haematological complications in 26% of patients, grade 3/4 infection in 3% of patients, both at the 700mg cyclophosphamide dose level with thromboembolic complications in 6%. Overall response rate is 81%. After a median follow-up of 21 months, projected 2 year progression free survival is 56% and the overall survival at 30 months is 80%. The combination of Lenalidomide, cyclophosphamide and dexamethasone is safe and effective combination in relapsed myeloma and warrants further investigation in phase 3 setting.

Mots clés: Medicine

Stephen Schey, Gareth J Morgan, Karthik Ramasamy, Beth Hazel, Sophie Corderoy, et al.. THE ADDITION OF CYCLOPHOSPHAMIDE TO LENALIDOMIDE AND DEXAMETHASONE IN MULTIPLY RELAPSED/RERACTORY MYELOMA PATIENTS; A PHASE I/II STUDY. British Journal of Haematology, 2010, 150 (3), pp.326. ⟨10.1111/j.1365-2141.2010.08250.x⟩. ⟨hal-00552599⟩