Multiple Myeloma (MM): Evolving Therapies Targeting Plasma Cells

Multiple Myeloma (MM) is a rare, chronic cancer of the plasma cells—antibody-producing white blood cells found in the bone marrow. In MM, abnormal plasma cells multiply uncontrollably, displacing healthy marrow and releasing harmful proteins (M-proteins), which can lead to bone damage, kidney dysfunction, anemia, and infections.

Though still considered incurable, MM is increasingly treated as a manageable chronic disease due to the development of novel therapies that target the disease from multiple angles. Early diagnosis and risk-adapted treatment strategies are essential for optimizing outcomes and improving quality of life.

Targeted Therapies in MM: Proteasome Inhibitors, IMiDs, and Anti-CD38 Antibodies

Modern treatment regimens for MM are often based on combinations of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies, followed by autologous stem cell transplant in eligible patients.

Proteasome Inhibitors (PIs)

• ●  Bortezomib (Velcade®)
• ●  Carfilzomib (Kyprolis®)

These drugs block the proteasome machinery that cancerous plasma cells rely on to dispose of abnormal proteins, leading to cell death. Bortezomib remains a cornerstone of induction therapy, while carfilzomib offers improved efficacy in relapsed settings.

IMiDs (Immunomodulatory Drugs)

• ●  Lenalidomide (Revlimid®)
• ●  Pomalidomide (Pomalyst®)

These agents modulate the immune system and inhibit myeloma cell growth. Lenalidomide is often used as maintenance therapy post-transplant and in frontline settings; pomalidomide is typically used in relapsed/refractory cases.

Anti-CD38 Monoclonal Antibodies

• ●  Daratumumab (Darzalex®)
• ●  Isatuximab (Sarclisa®)

These antibodies bind to CD38 on myeloma cells, triggering immune-mediated killing. Daratumumab, available in IV and subcutaneous forms, has become a mainstay of both frontline and relapsed regimens due to its excellent efficacy and tolerability.

Cellular Therapies and Future Innovations

CAR T-Cell Therapy

• ●  Idecabtagene vicleucel (Abecma®)
• ●  Ciltacabtagene autoleucel (Carvykti®)

CAR T-cell therapies targeting BCMA (B-cell maturation antigen) have shown remarkable response rates in heavily pretreated MM patients, many of whom had exhausted all other options. These therapies re-engineer a patient’s own T-cells to recognize and kill myeloma cells.

Bispecific Antibodies

Emerging bispecific T-cell engagers (BiTEs), such as teclistamab, elranatamab and talquetamab, bring T-cells into close contact with BCMA-expressing myeloma cells, offering an off-the-shelf alternative to CAR T.

Diagnostic Considerations

Diagnosis of MM is based on:

• ●  Monoclonal (M) protein in serum or urine
• ●  Clonal plasma cells ≥10% in bone marrow
• ●  CRAB criteria (elevated Calcium, Renal dysfunction, Anemia, Bone lesions)

Advanced imaging (PET-CT, MRI) and genomic profiling help stratify risk and guide therapy. Smoldering (asymptomatic) MM and MGUS (monoclonal gammopathy of undetermined significance) require close observation rather than immediate treatment.

Future Directions in MM Treatment

With the integration of triplet and quadruplet regimens, maintenance therapy, and novel cellular and immune-based therapies, survival in MM has improved dramatically over the past decade. Areas of ongoing research include:

• ●  Earlier use of CAR T and bispecific and trispecific antibodies
• ●  MRD-guided treatment duration
• ●  Targeting high-risk cytogenetic subtypes (e.g., del(17p), t(4;14))
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Today, the treatment landscape for MM is increasingly personalized and durable, offering long- term disease control and enhanced quality of life—even for patients with relapsed or refractory disease.