Relationship of response and survival in patients with relapsed and refractory multiple myeloma treated with pomalidomide plus low-dose dexamethasone in the MM-003 trial randomized phase III trial (NIMBUS)

Abstract

Relapsed/refractory multiple myeloma (RRMM) patients have poor overall survival (OS). Pomalidomide plus low-dose dexamethasone (POM + LoDEX) significantly extends OS in RRMM vs. high-dose dexamethasone. Survival of patients with stable disease (SD) was compared to patients with progressive disease (PD) or ≥ partial response (≥PR) at cycles (C) 3, 5, and 7. Among 302 patients randomized to POM + LoDEX, at C3 19.2% achieved ≥ PR, 38.4% SD, and 14.6% PD. Patients with SD at C3 (17.4%) and C5 (13.6%) showed improved responses at C7. Median OS from randomization by response at C3 was 22.4 months for ≥ PR (n = 58, HR 0.66; 95% CI 0.40-1.08, p = 0.0976 vs. SD), 16.2 months for SD (n = 116), and 6.3 months for PD (n = 44, HR 3.43; 95% CI 2.23-5.27, p < 0.0001 vs. SD). Similar patterns were observed for C5 and C7. Results show that POM + LoDEX should be a standard treatment after lenalidomide and bortezomib, including in SD patients.

Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma

“…As an encouraging result, the median OS in responders was not achieved after a median follow‐up of 28.0 months. As recently highlighted in data from the MM‐003 trial, we confirmed the absence of significant differences between response or stabilization and OS following pomalidomide initiation. Thus, a pomalidomide‐dexamethasone regimen should be a standard treatment after lenalidomide and bortezomib, including in patients with stable disease.…”

“…As recently highlighted in data from the MM-003 trial,17 we confirmed the absence of significant differences between response or stabilization and OS following pomalidomide initiation. In patients who respond to pomalidomide at 3 months, the duration of response exceeded 14 months in 50% of the patients.…”

“…pomalidomide-dexamethasone regimen. Except for peripheral neuropathy, our safety data are in line with those reported in clinical trials,6,[16][17][18]20,21 and have the major strength of adding additional information over a longer period (median follow-up longer than 18 months) with a "realworld" use. A total of 34 (54%) patients experienced at least 1 grade ≥3 AE, mainly hematologic or infectious.…”

Real‐world use of pomalidomide and dexamethasone in double refractory multiple myeloma suggests benefit in renal impairment and adverse genetics: a multi‐centre UK experience

“…Importantly, patients who achieved SD still appeared to derive a survival benefit with an OS of 13·1 vs. 3·6 months in those with PD. Post hoc analysis of the MM‐003 trial data has also shown this relationship between depth of response and survival (San Miguel et al , ; Moreau et al , ). In our cohort, patients with sustained disease response of at least 4 months had an estimated survival of nearly 2 years, suggesting that achieving disease stability increases the opportunity to receive further treatment at progression.…”

Pomalidomide in multiple myeloma

“…Indeed, patients with SD at the start of cycles 3, 5 and 7 showed no significant difference in OS than responding patients at the same time points [19]. The STRATUS study assessed safety and efficacy of pomalidomide (4 mg daily 21/28) + low-dose dexamethasone in the largest cohort to date of RRMM patients (N = 682) failing treatment with bortezomib and lenalidomide.…”