Pomalidomide-based vs. Proteasome Inhibitor-based Regimens for Multiple Myeloma: What Is the Optimal Sequence after First Relapse

Abstract

While significant advances have been made over the past two decades, treatment of multiple myeloma remains a challenge owing to the clinical trajectory of the disease. Following each relapse, disease remission periods tend to become progressively shorter as drug-resistant clones continually emerge. Lenalidomide is an immunomodulatory agent that is considered the backbone of frontline therapy for newly diagnosed multiple myeloma. Because of its widespread use and continuous administration until disease progression, lenalidomide refractoriness has become increasingly prevalent in clinical practice. Findings from several landmark clinical trials (such as CANDOR, IKEMA, IKARIA and APOLLO) provided ample evidence that helped establish pomalidomide and carfilzomib-based regimens as the mainstay of treatment in the early relapsed settings. Of note, clinical trials with novel agents such as T-cell engaging bispecific antibodies and antibody-drug conjugates are currently underway. Hence, navigating this crowded space of existing and emerging therapies for the purpose of selecting the optimal regimen to treat early disease relapse, might become increasingly complex over time. The primary objectives of this review article were to provide a succinct overview of the current literature and highlight the substantial heterogeneity in patient- and disease-specific characteristics that existed in the aforementioned trials which evaluated the efficacy of pomalidomide and proteasome-based regimens in relapsed/refractory multiple myeloma. Based on the available evidence, a treatment algorithm was developed which could be utilized as a practical tool to help guide treatment selection based on patient comorbidities, intolerance and refractoriness to prior therapies.