Phase II study of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide for sub-optimal response as second-line treatment for patients with multiple myeloma

Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma

“…The efficacy and safety findings of this matched-pairs analysis are supported by previously published data on bortezomib ± dexamethasone from prospective clinical trials, 4,5,[7][8][9][10][11]14,15,31 as well as by data from retrospective, [32][33][34] observational, 35,36 and compassionate use 37 studies in relapsed and/or refractory MM, and by data from previous prospective clinical trials of single-agent bortezomib in this setting. [1][2][3]38 The improved ORR and prolonged TTP and PFS observed in patients treated with bortezomibdexamethasone may be due, in part, to synergism between the two drugs, supported by pre-clinical data indicating that bortezomib enhances the anti-myeloma effects of dexamethasone, 39 or to an additive rather than synergistic effect of dexamethasone, 40 particularly in first relapse when patients may remain sensitive to glucocorticoids.…”

“…It should be noted that the 109 matched pairs of patients contributing to the data in this analysis only represent a subset of the overall study populations receiving bortezomib-dexamethasone in MMY-2045 and single-agent bortezomib in APEX and DOXIL-MMY-3001, which may explain the differences between the ORR, PFS, TTP, and OS data in this analysis and in the overall study results. [1][2][3]14 The rationale for performing a matched-pairs analysis to evaluate the benefit/risk profile of bortezomib-dexamethasone in comparison with bortezomib monotherapy was that this methodology can reduce selection bias due to differences in base-line prognostic factors and improve comparability of the patient populations between treatment groups, leading to reliable conclusions for crossstudy comparisons. Further to the primary matched-pairs analysis, the additional data analyses and sensitivity analyses conducted were supportive of the primary findings.…”

“…Data were included from the non-randomized cohort of patients treated with bortezomib-dexamethasone in the phase II MMY-2045 study (clinicaltrials.gov identifier: 00908232) 14 and from patients randomized to single-agent bortezomib in the phase III APEX study of bortezomib versus high-dose dexamethasone (clinicaltrials.gov identifier: 00048230) 1 and phase III DOXIL-MMY-3001 study of bortezomib plus liposomal doxorubicin versus bortezomib alone (clinicaltrials.gov identifier: 00103506), 3 the latter representing all the patient-level data on single-agent bortezomib from randomized studies accessible to the sponsor. Independent ethics committees/institutional review boards approved the trials, which were conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.…”

“…12 The combination of bortezomib and dexamethasone is also listed among the preferred regimens for salvage therapy in the US National Comprehensive Cancer Network Clinical Practice Guidelines for MM. 13 However, phase II data reporting on combination treatment with bortezomib-dexamethasone from first relapse in MM have only recently become available, 14,15 and prospective, randomized comparative data for bortezomib-dexamethasone versus single-agent bortezomib in relapsed and/or refractory MM are lacking.…”

“…Using patient-level data from a phase II study of bortezomib-dexamethasone, 14 and from the single-agent bortezomib arms of two phase III studies, 1,3 propensity score-matched pairs of patients were identified for a retrospective analysis of the efficacy and safety of second-line treatment with bortezomib-dexamethasone versus single-agent bortezomib. The matched-pair methodology was used to control for differences in base-line characteristics and to allow for meaningful cross-study comparisons. )…”