A recent review summarized the current knowledge and treatment paradigm of multiple myeloma, including recent advances and challenges in nanomedicine.
Multiple myeloma (MM) management has changed in recent decades as new therapy options emerged and the pathogenesis of the disease has become better understood. A review published in MedComm gives an overview of the current treatment landscape of MM, including recent advances in nanomedicine-based therapy options.
MM is the second most common hematological cancer, and it is characterized by malignant plasma cells that clonally expand and accumulate in bone marrow. The causes of MM are not clear, although suspected risk factors include both genetic and environmental characteristics. MM pathogenesis is also complicated, with multiple steps involved and high heterogeneity.
For MM to occur and progress, several initiating events must take place: chromosomal translocations, aneuploidy, genetic mutations, and epigenetic aberrations. Most patients first experience a premalignant stage called monoclonal gammopathy of undetermined significance, which is asymptomatic; then asymptomatic smoldering MM; and finally active MM, typically over the course of approximately 5 years.
The treatment landscape has expanded in recent decades and changed MM management. Therapies including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies(mAbs), chimeric antigen receptor (CAR) T-cell therapies, and other novel agents have positively impacted progression-free survival and overall survival (OS) for patients with MM.
The current treatment paradigm often includes induction therapy followed by consolidation and maintenance therapy. Standard of care regimens include lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd), and RVd plus daratumumab in patients who present with high-risk disease. Autologous stem cell transplantation is a key therapy option for eligible patients after initial treatment, as well as lenalidomide maintenance therapy, but many patients with MM relapse. The authors highlight the latest generation of PIs and IMiDs as favorable options for patients who relapse.
“The optimal choice of agents can be decided depending on several factors including patient features, previous treatments, and disease characteristics,” the authors wrote. They also highlighted nanomedicine-based approaches that could potentially address the issues of systemic toxicity and adverse events, which currently limit MM regimens.
Nanomedicine uses nanoscale biomaterials, categorized into organic nanomaterials and inorganic nanomaterials, as drug carriers and/or diagnostic tools. The properties and responsive conditions of these materials can be changed to facilitate different treatment goals, and using nanoparticle platforms for drug delivery can increase drug solubility and stability, control drug release, increase tumor site drug concentration, and reduce unwanted side effects.
Nanomedicine can improve the therapeutic index of chemotherapy drugs by altering their physicochemical properties, pharmacokinetics, and distribution in vivo. Several liposomes and polymeric nanoparticles are FDA approved for malignant neoplasms, and liposomal doxorubicin and liposomal vincristine are approved for MM and acute lymphoblastic leukemia. In both animals and humans, liposomal doxorubicin mitigated cardiac toxicity and improved drug delivery to the tumor site.
However, challenges remain in the application of nanomedicine in MM. It has shown promise in preclinical studies, but clinicians and patients have been less satisfied with its limited impact on OS. Large-scale output is also difficult due to a complex preparation process, and long-term data are needed to ensure safety and efficacy.
“MM is highly heterogeneous, and stemming from the heterogeneous expression levels of surface molecules on MM cells, there still exist limitations to achieving precise targeting,” the authors wrote. “Therefore, digging the highly unique surface marker of MM, creating dual-targeted nanoparticles, and optimizing the preparation are essential steps to improve the efficacy.” Drug resistance and relapse also remain challenging to navigate in patients with MM.
Despite the difficulties MM presents, there has been significant progress in recent years, and further research on novel agents and drug delivery systems could improve outcomes and minimize toxicity for patients with MM.
Yang P, Qu Y, Wang M, et al. Pathogenesis and treatment of multiple myeloma. MedComm (2020). Published online June 2, 2022. doi:10.1002/mco2.146