A recent review summarized the current knowledge and treatment paradigm of multiple myeloma, including recent advances and challenges in nanomedicine.
The management of multiple myeloma (MM) has changed over the past few decades as new treatment options have emerged and the pathogenesis of the disease has been better understood. A review published in MedComm provides an overview of the current treatment landscape for MM, including recent advances in nanomedicine therapy options.
MM is the second most common hematologic cancer and is characterized by malignant plasma cells that clonally expand and accumulate in the bone marrow. The causes of MM are not clear, although suspected risk factors include both genetic and environmental traits. 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 initially present with a premalignant stage, termed monoclonal gammopathy of undetermined significance, which is asymptomatic; then asymptomatic smoldering MM; and finally active MM, typically lasting about 5 years.
The treatment landscape has expanded in recent decades and MM management has changed. Therapies such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs), chimeric antigen receptor (CAR) T-cell therapies, and other novel agents have had a positive impact on progression-free survival and overall survival (OS) of the Patients impacted with MM.
The current treatment paradigm often involves induction therapy, followed by consolidation and maintenance therapy. Standard therapies include lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd), as well as RVd plus daratumumab in patients with high-risk diseases. Autologous stem cell transplantation is an important therapeutic option for eligible patients after initial treatment, as is lenalidomide maintenance therapy, but many patients with MM relapse. The authors highlight the latest generation of PIs and IMiDs as favorable options for relapsing patients.
“The optimal choice of agents can be decided depending on several factors, including patient characteristics, previous treatments and disease characteristics,” the authors write. They also highlighted nanomedicine-based approaches that could potentially address the issues of systemic toxicity and side effects that currently limit MM therapies.
Nanomedicine uses nanoscale biomaterials, categorized into organic nanomaterials and inorganic nanomaterials, as drug carriers and/or diagnostic tools. The properties and reaction conditions of these materials can be altered to achieve different treatment goals, and the use of nanoparticle platforms for drug delivery can increase drug solubility and stability, control drug release, increase drug concentration at the tumor site, and reduce unwanted side effects.
Nanomedicine can improve the therapeutic index of chemotherapeutic agents 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 moderated 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 physicians and patients have been less satisfied with its limited impact on OS. Large-scale production is also difficult due to a complex manufacturing process, and long-term data are needed to ensure safety and efficacy.
“MM is very heterogeneous, and due to the heterogeneous expression levels of surface molecules on MM cells, there are still limitations to achieve precise targeting,” the authors write. “Hence, unearthing MM’s highly unique surface marker, creating dual-target nanoparticles, and optimizing the preparation are essential steps to improve efficacy.” Drug resistance and relapse also remain a challenge in patients with MM.
Despite the difficulties MM presents, there have been significant advances in recent years, and further research into 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