EHA 2018 | The phase III OPTIMISMM study of pomalidomide, bortezomib and dexamethasone

The 23^rd Congress of the European Hematology Association (EHA) took place in Stockholm from 14–17 June 2018. On Saturday 16 June, an oral session took place during which, Paul G. Richardson from the Dana-Farber Cancer Institute (DFCI), Boston, USA, presented final data from the phase III OPTIMISMM trial. This study assessed the efficacy of pomalidomide (P), bortezomib (V) and low-dose dexamethasone (d) in comparison to the efficacy of Vd alone, in lenalidomide-exposed patients that had received 1–3 prior therapies.

Pomalidomide is an oral immunomodulatory drug (IMiD) which prevented proliferation of lenalidomide-resistant cells in pre-clinical assays. It is currently approved as a treatment for relapsed and refractory multiple myeloma (RRMM) patients that have received more than two prior regimens which include both lenalidomide and bortezomib, and who progressed on the last therapy. Since lenalidomide is an established upfront therapy, patients that become refractory to lenalidomide require other options, therefore the OPTIMISMM study sought to establish the efficacy of PVd in this patient population, with the primary endpoints of progression-free survival (PFS) and safety.

Key Data:

• Data cutoff = October 2017
• Patients (pts) (N = 559) were randomized 1:1 to receive either PVd (n = 281) or Vd (n= 278) in 21-day cycles
• Pomalidomide (P) = 4 mg/day on days 1–14; Bortezomib (V) = 1.3 mg/m² on days 1, 4, 8, and 11 of cycles 1–8 and on days 1 and 8 of cycle 9 onwards; Dexamethasone (d) = 20 mg/day (10 mg/day if aged > 75 years) on the same day as bortezomib treatment and the day after

Data is given as PVd treatment arm vs Vd treatment arm:

• Pt characteristics were well-balanced between the two treatment arms
• Refractory to last regimen = 70% vs 66%
• Prior lenalidomide = 100% in both arms; lenalidomide refractory = 71% vs 69%
• Prior bortezomib = 72% vs 73%; bortezomib refractory = 9% vs 12%
• Median number of prior lines of therapy = 2 (1 prior line in PVd = 40% and Vd = 41%)
• Median follow-up = 15.9 months
• Discontinuation: due to progressive disease (PD) = 65.8% vs 80.9%; due to adverse events (AEs) = 10.7 vs 17.6%
• Deaths (all causes) = 6.4% vs 3.2%
• Responses for: ITT group and pts with only 1 prior therapy:
  • Median PFS (months): = 11.20 vs 7.10; HR = 0.61 (95% CI, 0.49–0.77), P < 0.0001, and 20.73 vs 11.63; HR = 0.54 (95% CI, 0.36–0.82)
  • Overall response rate (ORR): 82.2% vs 50% and 90.1% vs 54.8%
  • ≥ Very good response rate (VGPR) = 52.7 vs 18.3% and 61.3% vs 22.6%
  • Median TTR (ITT) = 0.9 vs 1.4 months
  • Median duration of response (ITT) = 13.7 vs 10.9 months
• PFS was improved with PVd across all sub-groups
• Time to next treatment (TTNT) (months): 22.24 vs 8.51; HR = 0.42 (95% CI, 0.33–0.54), P < 0.001
• PFS2 (months): 22.44 vs 16.95; HR = 0.76 (95% CI, 0.59–0.99), P < 0.041
• Median treatment duration (months) = 8.8 vs 4.9
• Most common grade 3–4 AEs: Neutropenia = 42% vs 9%, infections = 31% vs 18%, and thrombocytopenia = 27% vs 29%, secondary primary malignancies (SPMs) = 3.2% vs 1.5%

Conclusion

Treatment with PVd reduced the risk of progression or death by 39%, compared to treatment with Vd alone, with this benefit consistent among patient subgroups, with the greatest benefit seen in patients that had received only one prior line of therapy. This study looked exclusively at lenalidomide-exposed patients, 75% of them refractory to lenalidomide, and therefore addresses the needs of a growing patient population for whom lenalidomide is no longer an option.