First Interim Analysis of HOVON 76: Lenalidomide Maintenance Following Non Myeloablative Allogeneic Stem Cell Transplantation in Patients with Multiple Myeloma.

Abstract 2285

Poster Board II-262

The phase II HOVON 76 study examines the efficacy and safety of maintenance treatment with lenalidomide 10 mgr daily for 21 days in a 28 day cycle for a maximum of 24 months following non myeloablative allogeneic stem cell transplantation (NMA allo-SCT). Patients with newly diagnosed Multiple Myeloma who had received intensive treatment including autologous stem cell transplantation (auto-SCT) and have a HLA identical sibling can be included. The NMA allo-SCT is performed within 2-6 months after the auto-SCT after a conditioning regimen of 2Gy total body irradiation. Immunosuppression consists of mycophenolate mofetil 15 mg/kg twice daily until day +84 and ciclosporin 4.5 mg/kg twice daily until day +120. Lenalidomide is started between 1 and 6 months after allo-SCT but preferably within 3 months. Before start the absolute neutrophil count must be ≥ 1.0 × 10⁹/L and platelets ≥ 75 × 10⁹/L. Acute graft versus host disease (GvHD) is an exclusion criterion to start with Lenalidomide except when affecting the skin for less than 50%.

If during treatment acute GvHD grade II or higher develops Lenalidomide is stopped and only re-initiated at a lower dose level of 5 mgr once GvHD resolves within 2 months. Dose reduction is also applied in case of other CTCAE grade 3 or higher toxicities, including bone marrow suppression.

As of January 2008, 31 patients have been included from 5 academic hospitals. Patients are predominantly male (68%) and median age is 53 years (range 32-65). Partial or complete treatment data are currently available from 24 patients.

The total of maximal CTCAE grade 3 and 4 toxicities reported were 50% and 17%, respectively and consists of blood/bone marrow toxicity grade 3 in 29% and grade 4 in 13%, metabolic/laboratory 25% and 4% and dermatology grade 3 in 8%. Seven serious adverse events have been reported, consisting of acute GvHD of the liver in 3 patients, 1 acute GvHD of the intestines, 1 pleural effusion after start of prednisone treatment for skin GvHD, 1 EBV reactivation with fever and malaise, 1 fever of unknown origin. All patients are alive at this moment.

After 1 cycle of Lenalidomide 6/24 patients (25%) went off protocol treatment mainly due to the development of acute GvHD (n=4), 1 because of progression and 1 refusal to continue. After cycle 2 another 4 patients (17%) went off protocol treatment due to adverse events and/or dose reductions below 5 mgr. Consequently only 58% of patients could continue with Lenalidomide maintenance after cycle 2. Of those patients, 2 went off protocol due to disease progression, 2 because of GvHD and 2 because of adverse events/dose reductions below 5 mgr after cycles 3-11.

In conclusion, the most encountered toxicity with Lenalidomide maintenance treatment after NMA allo-SCT is bone marrow toxicity and acute GvHD. The incidence of GvHD is not higher than expected from our previous NMA allo-SCT study HOVON 54 without Lenalidomide treatment. Because of this toxicity only 58% of patients could continue with treatment after cycle 2.

An update of the results with longer follow up will be presented.