Predictors of response to upfront bortezomib, lenalidomide and dexamethasone (VRd) in multiple myeloma.

Abstract

e20507 Background: Achievement of response to less than very good partial response (VGPR) after initial induction is an adverse prognostic factor for progression free survival (PFS) in multiple myeloma (MM). Triplet regimen has been demonstrated to be more effective as compared to doublets, with VRd being the preferred induction regimen in newly diagnosed multiple myeloma (NDMM) based on SWOG077 (43.5% VGPR or better). However, recent studies using quadruple combination, daratumumab-VRd, has shown deep response with 63% reached stringent complete remission (sCR) and CR. Balancing efficacy and toxicity in selecting induction regimen in treatment of MM is a challenge due to advanced age and comorbidity. Biomarkers that guided selection based on prediction for efficacy would be clinically useful. In this study we hypothesized that there is a subgroup of patients with MM that would not benefit from upfront VRd could be identified by biologic factors. Methods: For this retrospective study, we selected a cohort of patients with NDMM who were treated with upfront VRd to be evaluated for response after 3-6 cycles of treatment. We identified variables of risk classification that included cytogenetics, ISS stage, immunoglobulin subtype, light chain restriction, pre-treatment albumin level, bone marrow disease burden, end-organ involvement (hypercalcemia, anemia, renal insufficiency and lytic bone lesions), and presence of extra medullary disease. We analyzed the correlation between variables and response to therapy using Chi Square (Fisher’s Exact) test. Results: Among 175 patients treated in our institution starting April 2011 through May 2018, 120 patients received bortezomib-based regimen with 80% (96 subjects) received VRd and 20% (24 subjects) received Vd, with median age of 60.5 (39-74). After 3-6 cycles of VRd, 50% of patients achieved VGPR or better (48/96), 43% achieved partial response (PR) (43/96), 5% did not respond (5/96). Our data showed that immunoglobulin subtype has statistical significant impact on response to VRd; with increased incidence of VGPR or better in IgA myeloma (79%) as compared to IgG myeloma (37%) (P-Value < 0.0006). In IgG myeloma, we showed increased proportion of patients with PR (56%). Additionally, all 5 patients who did not respond to VRd had IgG myeloma. Other variables did not show statistically significant impact to response to upfront VRd. Conclusions: We conclude that IgG subtype MM predicts suboptimal response with VRd. Thus other regimens or four-drug regimen should be considered for upfront therapy in IgG subtype of MM.