Effect of Lenalidomide (LEN) Exposure on Response and Outcomes in Patients (Pts) with Lower-Risk Non-Del(5q) Myelodysplastic Syndromes (MDS)

Introduction : In the phase 3 MDS-005 study, LEN treatment was associated with a significant increase in transfusion independence (TI) vs placebo (26.9% vs 2.5%; P Methods : Eligible pts were age ≥ 18 years, had TD anemia due to International Prognostic Scoring System (IPSS)-defined Low- or Intermediate-1-risk MDS, lacked the del(5q) mutation, and were ineligible for or refractory to ESAs. Pts were randomized 2:1 to receive LEN 10 mg (n = 160) or placebo (n = 79) once daily (both in 28-day cycles). Pts randomized to LEN with creatinine clearance ≥ 40 to Results : Of 160 LEN-treated pts included in the analysis, 77 (48.1%) underwent ≥ 1 LEN dose reduction. A total of 73 pts experienced ≥ 1 dose reduction due to AEs, amounting to 102 dose reductions overall. Of these AE-related dose reductions, 47 were due to neutropenia, 33 due to thrombocytopenia, and 2 due to other hematologic conditions. Median time to first dose reduction was 85 days (interquartile range [IQR] 50-114 days). A total of 145 LEN-treated pts discontinued therapy: 52 discontinued due to AEs; 32 discontinued before the end of cycle 3, of which 23 were due to AEs. Of the 77 pts who had ≥ 1 dose reduction, 6 (7.8%) pts had a dose reduction in the first cycle; 37 (48.1%) pts had dose reductions during cycles 1-3. During the first 3 cycles of LEN, pts with ≥ 1 dose reduction received a lower median dose than those with no dose reductions (385 mg [IQR 318-520 mg] vs 660 mg [IQR 415-840 mg]). However, when analyzed over the course of the entire study, pts undergoing ≥ 1 dose reduction received a higher median cumulative dose than those with no dose reductions (950 mg [IQR 595-1,435 mg] vs 715 mg [IQR 370-1,660 mg]). Duration of treatment was also longer for pts with ≥ 1 dose reduction vs those with no dose reductions (172 days [IQR 140-391 days] vs 92 days [IQR 46-168 days]). Pts with ≥ 1 dose reduction were more likely to achieve RBC-TI ≥ 8 weeks than pts with no dose reductions (39% vs 16%; odds ratio [OR] 3.44 [95% confidence interval {CI} 1.63-7.26]). Pts with ≥ 1 dose reduction were also more likely to achieve clinical benefit ≥ 8 weeks vs pts with no dose reductions (47% vs 18%; OR 3.98 [95% CI 1.94-8.15]). Conclusions : In this post hoc analysis of the MDS-005 study, pts undergoing ≥ 1 LEN dose reduction had a longer duration of treatment, and were more likely to achieve RBC-TI and the composite endpoint of clinical benefit (RBC-TI ≥ 8 weeks, transfusion reduction ≥ 4 units pRBCs ≥ 8 weeks, Hb increase ≥ 1.5 g/dL ≥ 8 weeks, or CyR) than pts with no dose reductions. Disclosures Santini: Novartis: Consultancy, Honoraria; Onconova: Other: advisory board; Amgen: Other: advisory board; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Astex: Other: advisory board. Almeida: BMS: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Alexion: Speakers Bureau; Shire: Speakers Bureau. Fenaux: Celgene, Novartis, Teva: Honoraria; Celgene, Janssen, Novartis, Astex, Teva: Research Funding. Gatterman: Celgene Corporation: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Heinrich-Heine-Universitat Dusseldorf: Employment. Ozawa: Sumitomo Dainippon Pharma Co. Ltd: Research Funding; JCR Pharmaceutical Inc: Consultancy; Celgene Japan: Consultancy; Takara Bio Inc: Research Funding. Goldberg: COTA Inc: Employment; Novartis: Consultancy; Pfizer: Honoraria; Bristol Myers Squibb, Novartis: Speakers Bureau; Neostem: Equity Ownership. Weaver: Celgene Corporation: Employment, Equity Ownership. Sugrue: Celgene Corporation: Employment, Equity Ownership.