Pomalidomide Alone or in Combination With Low Dose Dexamethasone As Maintenance Following Induction With Pomalidomide And Low Dose Dexamethasone In Relapsed And Refractory Myeloma (Allg Mm14

Abstract

Background: Whilst the addition of dexamethasone to upfront therapy with Immunomodulatory (IMiD®) agents is important to mediate rapid reduction in disease burden, preliminary findings suggest that the NK stimulatory effects of IMiD® compounds are best harnessed without the co-administration of dexamethasone, and may be especially effective in the setting of minimal disease burden (in the maintenance setting for example) when some inherent immune recovery has occurred. However this has yet to be confirmed in a prospective clinical trial. Aims: To evaluate the effect of maintenance with POM alone (Arm 1) versus POM-LoDEX (Arm 2) on progression free survival (PFS), overall survival (OS), and kinetics of response (overall response rate (ORR)) in relapsed myeloma (MM) patients refractory to lenalidomide (R-LEN) demonstrating stable disease (SD) or better following salvage treatment with pomalidomide (POM) and low dose dexamethasone (LoDEX) induction. Methods: Multicentre, open-label, randomized phase 2 study of relapsed RLEN patients who had received>2 prior lines of therapy. POM 4mg days 1-21 (28 day cycle) was administered alone or in combination with LoDEX (40mg weekly) as maintenance following an induction with 4 cycles of POM and LoDEX. Treatment continued until toxicity or progression. Peripheral blood samples for immune studies were collected pre-induction and prior to cycles 1, 3, 6 and 10 of maintenance. Results: 154 patients from 11 sites were enrolled on to the study (M:F 80:74), with a median age of 67 years (range 35-88). Median number of prior lines of therapy was 4.5 (2-14). All patients had failed LEN (100%), 127 (82.5%) were also refractory to bortezomib (double refractory) and 94 (61%) had received a prior autologous stem cell transplant. 72 (47%) patients achieved SD or better with POM-LoDEX induction and were randomised, 35 to POM (Arm 1) and to 37 to POM-LoDEX (Arm 2). After a median follow-up of 19 months, median PFS for all patients from study entry was 4.2m (IQR 2.1 – 8.6m). PFS for randomised patients (from time of randomisation) was 2.7m for POM (arm 1) versus 5.6 for POM-LoDEX (arm 2) (p=0.39). The PFS hazard rate for Arm 2 was relatively constant compared to Arm 1 which started with a hazard rate double that of Arm 2 but dropped to less than half of the rate in Arm 2 by 15 months, suggesting that with longer follow-up, there may be an emergent advantage to maintenance with POM versus POM-LoDEX (Figure 1.). Median OS for all patients from study entry was 13.2m (IQR 6.3-26.8m). For randomised patients, median OS (from time of randomisation) was 19m for POM (Arm 1) versus 13.7m for POM-LoDEX (Arm 2) (p=0.41). ORR (≥PR) for all patients was 45.5% [CR=5 (3.3%), VGPR=13 (8.4%), PR=52 (33.8%)]. Clinical benefit rate (CBR) (≥MR) was 55.2% [MR=15 (9.7%)].

Summary/Conclusions: In patients with relapsed myeloma, after initial disease control/debulking is achieved with POM - LoDEX, induction, maintenance with single agent POM may be more effective for sustaining disease control than continuation of POM-LoDEX. Correlative studies are currently underway to further investigate the immunological mechanisms behind this observation. Show more