A recent review summarized the current knowledge and treatment paradigm for multiple myeloma, including recent advances and challenges in nanomedicine.
The management of multiple myeloma (MM) has changed over the past decades as new treatment options have emerged and the pathogenesis of the disease has been better understood. A exam Posted in MedComm provides an overview of the current MM treatment landscape, including recent advances in nanomedicine-based treatment options.
MM is the second most common hematologic cancer and is characterized by malignant plasma cells that multiply and clonally accumulate in the bone marrow. The causes of MM are unclear, although suspected risk factors include both genetic and environmental characteristics. The pathogenesis of MM 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 present with a precancerous stage called monoclonal gammopathy of undetermined significance, which is asymptomatic; then asymptomatic indolent MM; and finally active MM, usually over a period of about 5 years.
The treatment landscape has expanded over the past decades and changed the management of MM. Therapies including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs), chimeric antigen receptor (CAR) T cell therapies and other new agents have had a positive impact on 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 treatment regimens include lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd), and RVd plus daratumumab in patients with high-risk disease. Autologous stem cell transplantation is a key treatment option for eligible patients after initial therapy, 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 based on several factors, including patient characteristics, prior treatments, and disease characteristics,” the authors wrote. They also highlighted nanomedicine-based approaches that could potentially address issues of systemic toxicity and adverse events, which currently limit MM regimens.
Nanomedicine uses nanoscale biomaterials, classified as organic nanomaterials and inorganic nanomaterials, as drug carriers and/or diagnostic tools. The properties and response conditions of these materials can be modified to facilitate different treatment goals, and the use of nanoparticle platforms for drug delivery can increase drug solubility and stability, control the release of drugs, increase the concentration of drugs at the tumor site and reduce unwanted side effects.
Nanomedicine can improve the therapeutic index of chemotherapy drugs by modifying their physicochemical properties, pharmacokinetics and in vivo distribution. Several polymeric liposomes and nanoparticles are FDA-approved for malignant neoplasms, and liposomal doxorubicin and liposomal vincristine are approved for MM and acute lymphoblastic leukemia. In animals and humans, liposomal doxorubicin attenuated cardiac toxicity and improved drug delivery to the tumor site.
However, challenges remain in applying nanomedicine to MM. It has shown promise in preclinical studies, but clinicians and patients have been less satisfied with its limited impact on OS. Large-scale production is also difficult due to a complex preparation process, and long-term data is needed to ensure safety and efficacy.
“MM is highly heterogeneous, and due to the heterogeneous expression levels of surface molecules on MM cells, there are still limitations to achieving precise targeting,” the authors wrote. “Therefore, digging into the very unique surface marker of MM, creating dual-target nanoparticles, and optimizing preparation are critical steps to improve efficiency.” Drug resistance and relapses also remain difficult to manage in patients with MM.
Despite the challenges that MM presents, significant progress has been made in recent years, and further research into new agents and drug delivery systems may improve outcomes and minimize toxicity for patients with MM.
Yang P, QuY, Wang M, et al. Pathogenesis and treatment of multiple myeloma.MedComm (2020). Published online June 2, 2022. doi:10.1002/mco2.146