STRATUS (MM-010) trial to assess pomalidomide plus low-dose dexamethasone in refractory MM

The STRATUS (MM-010) phase-3b clinical trial, to further explore the efficacy of pomalidomide plus low-dose dexamethasone in patients with relapsed and/or refractory Multiple myeloma (RRMM), was led by Meletios Dimopoulos and Philippe Moreau, and the results published in Blood in July 2016. In the largest cohort to date, 682 patients (median age of 66 years and a median time from initial diagnosis of 5.3 years) with RRMM, were enrolled between November 2012 and December 2014.

Key Highlights:

• Total patients (pts) that received the study drug = 676
• Median follow-up = 16.8 months at data cut-off (May 4th 2015)
• Pts on treatment at cut-off = 104 (15.2%); discontinued treatment = 572 pts (83.9%)
• Median no. of prior treatment regimens = 5 (range, 2-18); most were refractory to lenalidomide and/or bortezomib: 95.9% of patients were refractory to lenalidomide
• Median treatment duration = 4.9 months
• ORR (ITT population) = 32.6% (95% CI: 29.0, 36.2); vGPR = 7.6% and CR = 0.6%
• Median time to response = 1.9 months (range, 0.5-17.5 months)
• Median DoR = 7.4 months (95% CI: 6.5, 8.7)
• ORR by sub-group:
  • Pts refractory to lenalidomide = 32.1%
  • Pts refractory to bortezomib = 32.9%
  • Pts refractory to both lenalidomide and bortezomib = 32.4%
  • Pts with ≤3 vs ≥3 prior lines of therapy = 28.5% vs 34.1%
  • Pts with/without renal impairment = 30.8% vs 33.9%
• Stable disease = 49.7% (339/682); median TTP = 4.7 months (95% CI: 4.2, 5.6)
• Median PFS (ITT) = 4.6 months (95% CI: 3.9, 4.9)
• PFS by patient sub-group:
  • Refractory to lenalidomide = 4.6 months (95% CI: 3.8, 4.9)
  • Refractory to bortezomib = 4.2 months (95%CI: 3.8, 4.8)
  • Refractory to lenalidomide and bortezomib = 4.2 months (95% CI: 3.8, 4.7)
  • Prior lines of therapy ≤ 3 vs >3 = 3.9 vs 4.6 months
  • With/without renal impairment = 3.8 vs 4.7 months
• Median OS (ITT) = 11.9 months (95% CI: 10.6, 13.4)
• Median OS by sub-group:
  • Refractory to lenalidomide, bortezomib, or lenalidomide and bortezomib = 11.9 months (95% CI: 10.6, 13.4)
  • Prior lines of therapy ≤ 3 vs >3 = 12.8 vs 11.9 months
  • With/without renal impairment = 10.2 vs 13.0 months

Safety:

• AEs leading to pomalidomide dose reductions (22.0%): neutropenia (5.9%), thrombocytopenia (4.3%), fatigue (2.5%), and pneumonia (2.4%)
• Median relative dose intensity = 0.901
• AEs leading to pomalidomide dose interruptions (66.3%): neutropenia (22.6%), thrombocytopenia (11.1%), pneumonia (10.2%)
• Main reason for discontinuation = progressive disease (62.2%), death (7.9%), AEs (5.9%), other causes (4.8%)
• Grade 3-4 hematologic AEs: neutropenia (49.7%), anemia (33.0%), thrombocytopenia (24.1%), and febrile neutropenia (5.3%)
• Grade 3-4 non-hematologic AEs: infection (28.1%) including 10.9% with pneumonia
• AEs were similar regardless of age
• Pneumonia of any grade = 111 patients (16.4%); majority resolved
• Serious AEs = 425 patients (62.9%)
• SPMs = 15 pts (5 invasive, 10 non-invasive); Incidence rate = 0.90/100 person years
• Deaths at data cut-off = 57.7% (safety population); 68.5% after treatment discontinuation
• Most common cause of death = disease progression (plasma cell myeloma = 35.2%, plasma cell leukemia = 0.4%, infections and infestations = 9.3%, general disorders = 5.6%)

Using the largest cohort to date of heavily pre-treated RRMM patients, the clinical benefit of pomalidomide plus low-dose dexamethasone was further demonstrated, as well as good overall tolerability. This corroborates the data from the previous MM-002 and MM-003 pivotal trials, and indicated little sub-group differences according to age or prior treatment regimen. This therefore provides viable treatment option for RRMM patients that have exhausted other avenues.