Analysis of Patient (Pt) Outcomes By Prior Treatment and Depth of Response in Stratus (MM-010), a Phase 3b Study of Pomalidomide + Low-Dose Dexamethasone (POM + LoDEX) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM)

Introduction: The introduction of newer agents, such as lenalidomide (LEN) and bortezomib (BORT), has resulted in improved survival outcomes in pts with RRMM (Kumar, Leukemia, 2012), and a greater depth of response has been associated with improved efficacy outcomes in RRMM (Harousseau, Haematologica, 2010). However, once pts become refractory to these newer agents, they experience poorer outcomes, with short overall survival (OS; Kumar, Leukemia, 2012). POM + LoDEX is approved for the treatment of pts with RRMM with ≥ 2 prior treatments, including LEN and BORT. A previous subanalysis of pts treated with POM + LoDEX in the MM-003 trial demonstrated that pts with a deeper response, as measured by a reduction in serum M protein, experienced longer OS and progression-free survival (PFS; San Miguel, ASH 2013). POM + LoDEX was shown to be safe and effective in the phase 3b STRATUS trial (MM-010; Dimopoulos, EHA 2015); here, we present the outcomes in this pt population by prior treatment and depth of response.

Patients and Methods: Pts with RRMM (progressive disease [PD] on or within 60 days of last prior treatment) with prior adequate alkylator therapy in whom LEN and BORT treatment failed were eligible. POM 4 mg was administered on days 1 to 21 of a 28-day cycle in combination with LoDEX (40 or 20 mg for pts aged ≤ 75 or > 75 yrs, respectively) on days 1, 8, 15, and 22. Treatment was continued until PD or unacceptable toxicity, and thromboprophylaxis was required for all pts. For this efficacy analysis, pts were grouped according to prior treatment history or reduction in serum M protein level.

Results: As of May 4, 2015, 682 pts were enrolled and 676 have received POM + LoDEX. In the intent-to-treat population, the median age was 66 yrs, 56% of pts were male, the median time since diagnosis was 5.3 yrs, and pts had received a median of 5 prior regimens. Approximately half of all pts (54.5%) had received prior thalidomide (THAL), and 186 vs 496 pts had received ≤ 3 vs > 3 prior regimens of therapy, respectively. Most pts were refractory to LEN (96%), BORT (84%), or both LEN and BORT (80%). The overall response rates (ORRs) were generally similar regardless of prior THAL, number of prior regimens, and LEN/BORT refractoriness. Pts who received prior THAL had an ORR of 30.4% compared with 35.2% for pts who did not receive prior THAL (Table). Similarly, for pts with a history of ≤ 3 vs > 3 prior antimyeloma regimens, ORR was 28.5% vs 34.1%. ORR did not appear to be impacted by refractory status to LEN and/or BORT (ORR, 32.1%-32.9%). PFS was comparable and independent of prior THAL exposure, number of prior regimens, and LEN/BORT refractoriness (PFS, 3.9-4.6 mos). Median OS was also similar for pts with or without prior THAL exposure (11.4 mos vs 12.0 mos, respectively), as was OS for pts with ≤ 3 vs > 3 prior regimens (12.8 mos vs 11.9 mos, respectively). Pts with LEN and/or BORT refractoriness had the same median OS of 11.9 mos. Analysis of PFS by serum M protein levels showed that a greater reduction in these levels was associated with a longer median PFS: for pts with a serum M protein reduction of < 25%, ≥ 25% to < 50%, and ≥ 50%, median PFS was 3.0, 4.8, and 7.6 mos, respectively.

Conclusions: The efficacy of POM + LoDEX in this heavily pretreated population was independent of treatment history. ORR, OS, and PFS were not significantly impacted by treatment history with THAL, having ≥ 3 prior regimens, or refractoriness to LEN and/or BORT. As shown previously with POM + LoDEX, there was a clear trend toward prolonged PFS in pts with a greater reduction in serum M protein levels. This analysis supports POM + LoDEX as a standard of care for pts with RRMM.

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