Pomalidomide Monotherapy for Relapsed Myeloma Is Associated with Excellent Responses and Prolonged Progression Free and Overall Survival.

Despite recent therapeutic improvements in the management of myeloma it remains an incurable disease. New therapies are therefore required. Pomalidomide (POM, Celgene) is a thalidomide derived immunomodulatory agent with similar preclinical spectrum of activity as lenalidomide. In Phase 1 studies we have previously demonstrated that POM monotherapy is well tolerated by patients with relapsed myeloma determining a maximum tolerated dose of 2mg od or 5mg on alternate days (Schey et al. JCO 2004; Streetly et al. BJHaem 2008). The toxicity profile was acceptable and overall response rates of 54 and 50% were observed with daily and alternate day dosing respectively. The current study examines long term responses, progression and survival outcomes. Patients were entered into the POM daily dosing or alternate day dosing Phase 1 studies between March 2001 and September 2003 and continued to receive treatment with POM until progressive disease (PD) or Grade 3 or greater non-haematological toxicity. Patients with PD were eligible to receive dexamethasone in addition to POM. POM became unavailable in May 2005 and patients still receiving drug were switched to receive lenalidomide. All patients gave informed consent.

44 patients received treatment with POM at a dose of 1mg alternate days – 10mg od. A median of 3 (range 1 – 8) prior lines of therapy had been received. POM was received for a median of 9.3 months (1 – 53). Following POM withdrawal 8/44 patients who had not developed PD subsequently received lenalidomide from a median of 30 months after starting POM. Overall responses by IMWG criteria to POM monotherapy were: CR 13.6%, VGPR 4.5%, PR 34%, MR 9%, SD 29.5% and PD 7% giving an overall response rate (>PR) of 52%. Dexamethasone was introduced for PD for 10 patients and prolonged SD for 1 patient. 5/10 of these patients had >MR response to the addition of dexamethasone. With a median follow-up of 28 months the median PFS was 13.7 months and median OS was 28 months. Patients who had a PR response or better received POM for a median of 17.5 months and had improved PFS (median 19.8 months) and OS (median 42 months). 8/44 patients subsequently received lenalidomide. 7/8 of these patients have now developed PD at a median 26 months from commencing lenalidomide and 74 months from starting POM.

POM is a very well tolerated drug with excellent long term responses observed in this Phase 1/2 setting predominantly as monotherapy. Phase 2 studies are ongoing and results of these are awaited with interest.

Streetly:Celgene: Honoraria. Schey:Celgene: Honoraria.