Relapsed/refractory patients

Updated results from MM-003 trial of pomalidomide plus low-dose dexamethasone: depth of response analysis

The MM-003 clinical trial compared the use of pomalidomide plus either low- or high- dose dexamethasone, for the treatment of patients with relapsed and refractory (RR) Multiple Myeloma (MM), after failed treatment with bortezomib and lenalidomide. A favorable outcome was observed for pomalidomide plus low-dose dexamethasone. An updated analysis of patient outcome was assessed according to treatment history and depth of response, and was published in Haematologica in June 2015, by Jesus San Miguel from Clinica Universidad de Navarra, CIMA, Pamplona, Spain and colleagues. This secondary analysis (at data cut-off September 1st, 2013) assessed progression-free survival (PFS), overall survival (OS), overall response rate (ORR; the proportion of patients achieving a PR or better), time to progression (TTP), duration of response (DOR), safety, and quality of life. Study design and treatment regimen are detailed in a previous MMHub article.

Key Findings:

  • Patients (pts) were randomly assigned into pomalidomide plus low-dose dexamethasone (POM+LoDEX) or pomalidomide plus high-dose dexamethasone (POM+HiDEX)
  • Median follow-up = 15.4 months; median no. of prior treatments = 5 (in both arms)

Data are given as: POM+LoDEX vs POM+HiDEX:

  • Patients (pts) refractory to LEN = 95% vs 92%
  • Pts refractory to both LEN and BORT = 75% vs 74%
  • Median PFS (in ITT population) = 4.0 vs 1.9 months; HR = 0.50; (P<0.001)
  • Median OS (in ITT population) = 13.1 vs 8.1 months; HR = 0.72; (P=0.009); (OS advantage observed, despite 56% pts in HiDEX arm receiving subsequent POM)
  • ORR (PR or better) = 32% vs 11%; (P<0.001); MR or better = 40% vs 15%
  • Median DOR (for patients with a PR or better) = 7.5 vs 5.1 months; P=0.031
  • Pts that achieved disease control (stable disease or better) = 82% vs 61%
  • PFS in pts with stable disease control = 4.9 vs 2.8 months; P<0.001
  • Pts whose best response was stable disease = 3.5 vs 2.5 months; P=0.034
  • Pts who did not respond within the first 2-3 treatment cycles subsequently achieved a response (or PR): 58 vs 5, 16 vs 4, and 20 vs 5 pts responded within 9 weeks, 9-13 weeks, and after 13 weeks, respectively
  • Pts who had LEN-refractory disease:
    • PFS: HR = 0.51 (95% CI, 0.41–0.64); OS: HR = 0.70 (95% CI, 0.55–0.90))
  • Pts refractory to LEN as their last prior treatment:
    • PFS: HR = 0.41 (95% CI, 0.28–0.62); OS: HR = 0.56 (95% CI, 0.36–0.88))
  • ORR via prior therapy:
    • pts refractory to LEN (n=286), BORT (n=238), or both (n=225) = 30% vs. 31% vs 29%
    • pts refractory to LEN (n=85) or BORT (n=134) as last prior therapy = 33% vs 34%
    • pts with (n=173) and without (n=129) prior treatment with THAL = 31% vs 34%
    • pts with prior stem cell transplant = 31%
  • TTP compared with last line of therapy:
    • LoDEX = 4.7 vs 4.4 months; HR = 0.79; (P=0.008)
    • HiDEX = 2.1 vs 4.3 months; HR = 1.76; (P<0.001).
  • Multivariate analysis concluded that no variable relating to the number or type of prior treatments was a significant predictor of PFS or OS
  • Depth of response was assessed by analyzing PFS and OS according to the degree of reduction in M-protein levels on POM+LoDEX treatment:
    • Median PFS with reductions of < 25%, ≥ 25%, and ≥ 50% = 2.3, 7.4, and 8.4 months, respectively
    • Median OS with reductions of < 25%, ≥ 25%, and ≥ 50% = 7.5, 17.2, and 19.9 months, respectively
    • This association was observed regardless of age or cytogenetic risk status

These updated results with a longer follow-up period confirmed a significant PFS benefit for patients treated with pomalidomide plus low-dose dexamethasone, and this effect carried through into assessment for depth of response, regardless of patient age, prior treatment or cytogenetic risk status. Therefore, pomalidomide plus low-dose dexamethasone is a beneficial treatment pathway for patients with RRMM, for whom other therapies have been exhausted. 

 

References
  1. San Miguel JF. et al. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. Haematologica. 2015 Oct;100(10):1334-9. DOI: 10.3324/haematol.2015.125864. Epub 2015 Jul 9.
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