Pomalidomide 3rd Line Versus 4^th Line for RRMM

Background. Pomalidomide in association with dexamethasone is approved for RRMM in 3^rd line and beyond based on the MM-003 multicenter international phase 3 study that demonstrated greater efficacy for Pomalidomide plus dexamethasone over high dose dexamethasone. However, MM-003 mainly recruited advanced RRMM with a median of 5 prior lines. Few data is available regarding real life Pomalidomide-based treatment in 3^rd and 4^th line RRMM.

The aim of this study was to study efficacy and safety of Pomalidomide-based treatment in 3^rd and 4^th line RRMM.

Methods. We studied 108 consecutive RRMM treated with Pomalidomide-based treatment in 3^rd and 4^th line in a multicenter-based study. All assessment made according to IMWG.

Results. The median age was 62.5 (range, 30-86), with 36% older than 65 years, sex ratio M/F 1.25 and ISS disease stage 2 or 3 in 58%. 100% were exposed to bortezomib and refractory to Lenalidomide. 52 patients (48%) had pomalidomide-based therapy as 3^rd, and 56 (52%) as 4^th line. 73% of patients received a double-based therapy (Pomalidomide plus Dexamethasone) and 27% received a triple based therapy (Pomalidomide, Cyclophosphamide and Dexamethasone).

Overall ORR was 55%, with 20% ≥VGPR including 5% CR, and was not statistically different in 3^rd versus 4^th line, and with PCd versus Pd, although the former was always better.

With a median f-up of 45 months, overall 77% and 49% had relapsed and died, respectively, with significantly less in benefit to combination and 3^rd line compared to Pd and 4^th line (p=0.020). The median PFS was 6 (CI95% 2.3;9.6) and 9 (5.5;12.5) months in 3^rd and 4^th line (p=0.04), and 6 (CI95% 2.8;9.2) and 12 (8.5;15.5) months in Pd and PCd (p=0.04), respectively. Interestingly, the estimated 3 years PFS for 3^rd line and PCd was 34% and 32% respectively, greatly superior to 4^th line and Pd, 13% and 18%, respectively. Similarly, the median OS from start of Pomalidomide was not reached in 3^rd and in PCd lines versus 23months (5;49), (p=0.04), and 32 months (5;-) for 4^th line and Pd use, respectively.

Pomalidomide was never permanently discontinued for safety issues, but 30 (28% of patients had to reduced pomalidomide dose, 25% to N-1 that is 3mg/d and 3% at N-2 that is 2mg/d. Expectedly, more patients (increased by 10%) had to reduce pomalidomide dose in 4^th line compared to 3^rd line, although it was not statistically significant, but not with PCd versus Pd. Indeed Cyclophosphamide but not pomalidomide is reduced in modified in dose or scheme when facing safety issues. No patient died related to adverse events. AEs leading to pomalidomide-based modification in schema included hematological in 40% and non hematological AEs in 12% of patients. Overall, the most common adverse events grade 3 or 4 were neutropenia (22%), anemia (11%), thrombocytopenia (7%) and infectious disease (5%).

Conclusion. Pomalidomide-based therapy demonstrates efficacy in the real life with a manageable safety profile. We demonstrate herein that early use and combination improves MM on pomalidomide in the real life. Further prospective studies are warranted to confirm this data on a larger MM population.