Nearly all patients with multiple myeloma eventually relapse or become refractory to treatment. Lenalidomide is increasingly administered in the frontline until disease progression or intolerance to therapy, resulting in the need for highly effective, lenalidomide-sparing options. In this study, carfilzomib plus daratumumab and dexamethasone were evaluated against lenalidomide-sparing, pomalidomide-containing triplets using matching-adjusted indirect comparison in the absence of head-to-head data. The analyses utilized long-term follow-up data from the CANDOR study (NCT03158688). Treatment with carfilzomib, daratumumab, and dexamethasone resulted in significantly longer progression-free survival (hazard ratio 0.60 [95% confidence interval: 0.37, 0.88])vs. pomalidomide plus bortezomib and dexamethasone, and numerically longer progression-free survival (hazard ratio 0.77 [95% confidence interval: 0.50, 1.08]) vs. daratumumab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma and previous lenalidomide exposure, the majority of whom were lenalidomide refractory. Carfilzomib plus daratumumab and dexamethasone offers a highly effective, lenalidomide-sparing treatment option for this population.

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http://dx.doi.org/10.1080/10428194.2023.2300051DOI Listing

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Article Synopsis
  • Multiple myeloma (MM) is the second most prevalent blood cancer worldwide, traditionally viewed as aggressive and deadly.
  • Recent advancements in treatment, such as proteasome inhibitors, monoclonal antibodies, immunomodulators, and corticosteroids, have improved patient outcomes significantly.
  • Due to innovative combination therapies and ongoing research, there is growing optimism for future treatments, aiming to make MM more manageable and potentially curable.
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Therapy adherence can significantly influence the outcome of cancer patients. The prospective, non-interventional CARO study (NCT02970747) investigated adherence, effectiveness, and safety of carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) in the German real-world setting. In total, 359 patients were included at 69 sites.

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Aims: Limited head-to-head data exist for daratumumab plus pomalidomide and dexamethasone (DPd) and non-pomalidomide-containing triplet regimens to treat relapsed/refractory multiple myeloma (RRMM). This study conducted population-adjusted indirect comparisons of overall survival (OS) for DPd vs. daratumumab, carfilzomib, and dexamethasone (DKd) and daratumumab, bortezomib, and dexamethasone (DVd).

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In newly diagnosed multiple myeloma (NDMM), measurable residual disease (MRD) status is prognostically important, but its role in treatment-decisions remains unclear. In a phase II trial (NCT04113018), we assessed daratumumab, carfilzomib, lenalidomide and dexamethasone (Dara-KRd) induction followed by a next generation sequencing (NGS) based MRD-adapted strategy. The primary endpoint was rate of complete response and stringent complete response (≥CR) after induction.

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Objective: To assess the cost-effectiveness of adding daratumumab to carfilzomib and dexamethasone (KdD) in patients with relapsed or refractory multiple myeloma (RRMM).

Materials And Methods: A Markov model was established to estimate health and economic outcomes of carfilzomib and dexamethasone (Kd) with or without daratumumab for RRMM patients over a lifetime horizon. The patients and intervention of the two arms were modeled according to the CANDOR trial.

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