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

Abstract

Pomalidomide is a distinct oral IMiD(®) immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30.

Copyright© Ferrata Storti Foundation.

Figures

Figure 1.

Disposition of MM-003 trial participants as of September 1, 2013. AE: adverse event; HiDEX: high-dose dexamethasone; LoDEX: low-dose dexamethasone; PD: progressive disease; POM: pomalidomide; Tx: treatment.

Figure 2.

Forest plot of progression-free survival (A) and overall survival (B) based on prior treatment. aNumber of events/number of patients. BORT: bortezomib; HiDEX: high-dose dexamethasone; HR: hazard ratio; ITT: intent-to-treat; LEN: lenalidomide; LoDEX: low-dose dexamethasone; POM: pomalidomide; ref: refractory; SCT: stem cell transplant; THAL: thalidomide; Tx: treatment.

Figure 3.

Response (by International Myeloma Working Group criteria) to POM + LoDEX treatment by prior therapy. Percentages may not sum to 100% due to rounding. BORT: bortezomib; LEN: lenalidomide; LoDEX: low-dose dexamethasone; POM: pomalidomide; PR: partial response; SCT: stem cell transplant; THAL: thalidomide; Tx: treatment; VGPR: very good partial response.

Figure 4.

TTP on study compared with last prior therapy. HiDEX: high-dose dexamethasone; HR: hazard ratio; LoDEX: low-dose dexamethasone; POM: pomalidomide; TTP: time to progression; Tx: treatment.

Figure 5.

PFS (A) and OS (B) by depth of response measured by degree of M-protein level reduction for patients assigned to POM + LoDEX. LoDEX: low-dose dexamethasone; OS: overall survival; PFS: progression-free survival; POM: pomalidomide.