Annette Lam

Analysis of Real-World Data on Overall Survival in Multiple Myeloma Patients With ≥3 Prior Lines of Therapy Including a Proteasome Inhibitor (PI) and an Immunomodulatory Drug (IMiD), or Double Refractory to a PI and an IMiD

BACKGROUND This retrospective study evaluated the treatment patterns in and overall survival (OS) of multiple myeloma (MM) patients who were refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) or who had received three or more prior lines of therapy (LOTs) including a PI and an IMiD. METHODS Electronic health records in the IMS LifeLink and OPTUM databases were screened for indexing periods of 2000-2014 and 2007-2014, respectively. Patients who were refractory to both a PI and an IMiD (criterion 1) or who received three or more prior LOTs (including a PI and an IMiD) and showed disease progression within 60 days of their most recent regimen (criterion 2) comprised the eligible population. Median OS from time of last LOT was assessed for the full cohort, cohorts meeting criteria 1 and 2, and clinically important subgroups. RESULTS Of 3,929 and 3,837 patients with MM diagnoses evaluated in the IMS LifeLink and OPTUM databases, 500 and 162 met the eligibility criteria, respectively. Similar median OS was observed for eligible patients in the IMS LifeLink and OPTUM databases (7.9 vs. 7.9 months; p = .5358). In subgroup analyses of the IMS LifeLink data set, median OS was longer in patients <65 years of age than it was for those ≥65 years at eligibility (9.5 vs 6.7 months; p < .01) and in patients with good or unreported versus poor performance status at last claim (7.8 or 8.8 vs. 2.9 months; p < .0001). CONCLUSION The findings of this survival analysis suggest that outcomes for these patients remain poor despite the availability of newer agents. IMPLICATIONS FOR PRACTICE This real-world retrospective study of electronic health records examines the survival outcomes of patients with multiple myeloma who are heavily pretreated or highly refractory to currently approved treatments, including recently approved proteasome inhibitors and immunomodulatory drugs. This survival analysis showed that outcomes for these patients remain poor despite the availability of newer agents, with median overall survival of approximately 8 months. These findings highlight a critical need to develop novel therapies for these patients and also serve as a reference point against which emerging agents for heavily pretreated or highly refractory disease may be evaluated.

Daratumumab monotherapy compared with historical control data in heavily pretreated and highly refractory patients with multiple myeloma: An adjusted treatment comparison.

Daratumumab is a human CD38‐directed monoclonal antibody approved in the United States as monotherapy for patients with multiple myeloma (MM) who have received ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD, and in combination with lenalidomide/dexamethasone or bortezomib/dexamethasone for patients with MM who have received ≥1 prior LOT. This study compared the efficacy of daratumumab monotherapy versus historical controls through adjusted treatment comparison. Patient‐level data were pooled from two daratumumab monotherapy studies (16 mg/kg; GEN501 and SIRIUS) and two independent US databases (IMS LifeLink and OPTUM), which reflect treatments used in real‐world patients with MM who received ≥3 prior LOTs or were double refractory to a PI and an IMiD. Using a multivariate proportional hazards regression model, the relative treatment effect of daratumumab versus historical controls was estimated, adjusting for imbalances in characteristics between cohorts. Baseline characteristics that differed between patients treated with daratumumab (N = 148) and historical control (N = 658) were prior treatment with pomalidomide (55% vs 15%) or carfilzomib (41% vs 28%) and triple/quadruple refractory status (64% vs 14%). The adjusted overall survival–hazard ratio (OS‐HR) for daratumumab versus historical control was 0.33 (95% confidence interval, 0.24‐0.46) compared with 0.46 (0.35‐0.59) for unadjusted HR. Impact of adjustment was mainly driven by refractory status and prior pomalidomide/carfilzomib exposure. This adjusted treatment comparison suggests that daratumumab demonstrates improved OS compared with historical control data in heavily pretreated and highly refractory MM patients.

A Comparison of the Efficacy of Immunomodulatory-containing Regimens in Relapsed/Refractory Multiple Myeloma: A Network Meta-analysis

&NA; A systematic review and network meta‐analysis were conducted to compare the clinical efficacy of immunomodulatory drug‐containing regimens in patients with relapsed or refractory multiple myeloma. Daratumumab plus lenalidomide and dexamethasone had a significant advantage in improving progression‐free survival of patients compared with other immunomodulatory drug‐containing regimens. Background: Previous network meta‐analyses combined studies of immunomodulatory drug (IMiD)–containing and IMiD‐free regimens, despite a lack of head‐to‐head randomized controlled trials to robustly link them. However, patients with relapsed or refractory multiple myeloma (RRMM) treated with IMiD‐containing regimens differ from those treated with IMiD‐free regimens, especially relating to treatment history, which is an important treatment‐effect modifier requiring clinical consideration when evaluating the most appropriate subsequent treatment options. A need exists to separately assess the efficacy of treatment regimens for patients who are suitable candidates for IMiD‐containing and IMiD‐free regimens. The presented analyses will enable clinicians to assess the best regimens to use in patients suitable for IMiD‐containing regimens. Materials and Methods: We used a Bayesian network meta‐analysis to compare IMiD‐containing regimens in patients with RRMM. Additionally, subgroup analyses were conducted stratified by previous therapy line, previous bortezomib therapy, and previous lenalidomide therapy. Results: The results indicated that triplet combinations are more effective than doublet combinations. Of the triplet combinations, daratumumab, lenalidomide, dexamethasone (DRd) was significantly better in improving progression‐free survival in patients with RRMM than were other IMiD‐containing regimens (lenalidomide, dexamethasone [Rd]: hazard ratio [HR], 0.37; carfilzomib, Rd: HR, 0.54; elotuzumab, Rd: HR, 0.54; ixazomib, Rd: HR, 0.50). Similar trends were observed for overall survival and overall response. DRd showed the greatest probability of being the best treatment for all clinical efficacy outcomes. The subgroup analyses results were consistent with the base‐case results. Conclusion: In patients with RRMM who are suitable for an IMiD‐containing regimen, DRd showed clear advantages in survival and response outcomes compared with other IMiD‐containing regimens.

Propensity score matching analysis to evaluate the comparative effectiveness of daratumumab versus real-world standard of care therapies for patients with heavily pretreated and refractory multiple myeloma

Abstract Daratumumab is a CD38-directed monoclonal antibody approved for treating multiple myeloma (MM). Propensity score matching (PSM) based on individual patient data (IPD) was conducted to compare overall survival (OS) and progression-free survival (PFS) for daratumumab versus real-world standard of care (SOC). IPD for patients with relapsed and refractory (RR) MM treated with daratumumab monotherapy were from the GEN501 and SIRIUS studies; IPD for patients treated with SOC were from an International Myeloma Working Group (IMWG) chart review of patients with RRMM. Prior to PSM, patients treated with daratumumab had significantly longer OS (median 20.1 vs. 10.1 months, hazard ratio [HR] = 0.51 [0.39–0.67]) and PFS (median 4.0 vs. 2.8 months, HR = 0.73 [0.58–0.92]) than patients treated with SOC therapies. After PSM, daratumumab maintained a significantly prolonged OS (19.9 vs. 9.2 months, HR = 0.44 [0.31–0.63]) and PFS (3.9 vs. 1.6 months, HR = 0.56 [0.42–0.74]) compared with SOC.

Economic Burden of Relapsed or Refractory Multiple Myeloma: Results from an International Trial.

The direct cost of relapsed or refractory multiple myeloma (RRMM) is documented; indirect costs are being explored. Healthcare payers seek cost‐offsets from therapies that improve clinical outcomes but challenge budgets; employers seek lower absenteeism and better productivity. Study goals were to: (i) identify direct and indirect economic factors of RRMM, and (ii) explore longitudinal relationships between clinical, economic, and health‐related quality of life (HRQoL) assessments.