J Clin Oncol 31, 2013 (suppl; abstr 8510)
Jesùs F. San-Miguel, Katja C. Weisel, Philippe Moreau, Martha Lacy, Kevin W. Song, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Anne Banos, Albert Oriol Rocafiguera, Xin Yu, Lars Sternas, Christian Jacques, Mohamed H. Zaki, Meletios A. Dimopoulos; Hematology, Hospital Universitario de Salamanca, Salamanca, Spain; Hematology & Oncology, Department of Medicine, University Hospital Tuebingen, Tuebingen, Germany; Hematology, University Hospital Hotel-Dieu, Nantes, France; Mayo Clinic, Rochester, MN; Vancouver General Hospital, Vancouver, BC, Canada; Department of Hematology, University Hospital Leuven, Leuven, Belgium; Centre Hospitalier Lyon Sud/Hospices Civils de Lyon, Pierre-Bénite, France; Universitätsklinikum Heidelberg, Heidelberg, Germany; Hematology, Centre Hospital de la Côte Basque, Bayonne, France; Institut Catala d'Oncologia, HGTiP, Barcelona, Spain; Celgene Corporation, Summit, NJ; Alexandra Hospital, Athens, Greece
Background: RRMM patients (pts) who have exhausted treatment (Tx) with bortezomib (BORT) and lenalidomide (LEN) or thalidomide have a poor prognosis with short overall survival (OS). HiDEX is a well-established standard Tx in RRMM. POM has demonstrated clinical efficacy in pts refractory to LEN and BORT. MM-003 compared POM + LoDEX vs. HiDEX in RRMM pts who failed LEN and BORT and who progressed on their last Tx.
Methods: Pts must have been refractory to last prior Tx (progressive disease [PD] during Tx or within 60 days) and failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination). Pts were randomized 2:1 to receive 28-day cycles of POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged > 75 y) weekly or DEX 40 mg (20 mg for pts aged > 75 y) D1–4, 9–12, and 17–20. Tx continued until PD or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included OS, overall response rate (ORR; ≥ partial response), and safety. Analyses were based on intent to treat. Results: 455 pts were randomized to POM + LoDEX (n = 302) or HiDEX (n = 153). The median number of prior Tx was 5 (range 1-17). 72% were refractory to LEN and BORT. Median follow-up was 4 months. POM + LoDEX significantly extended median PFS (3.6 vs. 1.8 months, HR = 0.45, P < .001) and OS (not reached vs. 7.8 months, HR = 0.53, P < .001) vs. HiDEX. The OS benefit was observed despite 29% of HiDEX pts receiving POM after PD. The trial met the primary endpoint of PFS, crossed the upper boundary for OS superiority, and the Data Monitoring Committee recommended crossover from HiDEX to POM ± DEX. With updated data, the ORR was 21% for POM + LoDEX vs. 3% for HiDEX (P < .001) and 24% vs 3% for pts randomized ≥ 6 months post-enrollment (P < .001). The most frequent grade 3/4 adverse events (AEs) for POM + LoDEX vs. HiDEX were neutropenia (42% vs. 15%), anemia (27% vs. 29%), and infection (24% vs. 23%). Discontinuation due to AEs was infrequent (7% vs. 6%). Updated data will be presented.
Conclusions: POM + LoDEX significantly extended PFS and OS vs. HiDEX in pts who failed LEN and BORT. POM + LoDEX should become a standard of care in RRMM pts who have exhausted Tx with LEN and BORT.
Clinical trial information: NCT01311687