Understanding the Role of Pomalidomide in Relapsed or Refractory Multiple Myeloma

Relapsed or Refractory Multiple Myeloma

Multiple myeloma is a type of blood cancer that affects plasma cells, which are a type of white blood cell that produces antibodies to help fight infections. In multiple myeloma, abnormal plasma cells grow uncontrollably in the bone marrow and produce an abnormal protein called monoclonal protein or M protein. 

Relapsed or refractory multiple myeloma (RRMM) refers to a stage in the disease where the cancer has either returned after a period of improvement with treatment (relapsed) or has become resistant to treatment and no longer responds to therapy (refractory) 

This can lead to a variety of symptoms, including bone pain, anemia, fatigue, kidney damage, and increased risk of infections. Multiple myeloma is a rare disease, but it is the second most common type of blood cancer. It is usually diagnosed through blood tests, bone marrow biopsy, and imaging tests. Treatment options for multiple myeloma include chemotherapy, immunotherapy, stem cell transplantation, and targeted therapy.

Role of Pomalidomide in Relapsed or Refractory Multiple Myeloma

Pomalidomide is a third-generation immunomodulatory drug used in the treatment of relapsed or refractory multiple myeloma (RRMM). Pomalidomide is indicated for patients with multiple myeloma who have received at least two prior therapies including both lenalidomide and a proteasome inhibitor such as bortezomib, carfilzomib, or ixazomib, and have demonstrated disease progression on or within 60 days of completion of the last therapy. 

Pomalidomide is also used in triplet regimens for previously treated myeloma. Pomalidomide has shown impressive results in patients who are refractory to other treatments. It has direct myeloma cell tumoricidal effects by activating proteasomal degradation of Ikaros and Aiolos (transcription factors that play critical roles in the regulation of gene expression) interaction with bone marrow stromal cells, and inhibition of angiogenesis. 

How Pomalidomide works?

• Pomalidomide, a third-generation immunomodulatory drug, exerts its mechanism of action through multiple pathways. It inhibits tumor cell proliferation and induces apoptosis while enhancing T cell and natural killer cell-mediated immunity. 
• By inhibiting pro-inflammatory cytokines like TNF-alpha and IL-6, it modulates immune responses. Its primary target is the protein cereblon, inhibiting ubiquitin ligase activity. Pomalidomide also acts as a transcriptional inhibitor of COX2, directly inhibiting angiogenesis and myeloma cell growth. It upregulates interferon-gamma, IL-2, and IL-10, while downregulating IL-6, contributing to its anti-angiogenic and anti-myeloma effects. 
• Additionally, pomalidomide regulates p21WAF expression and interferon regulatory factor 4, inducing tumor cell apoptosis. 

Clinical trials demonstrate significant improvements in progression-free and overall survival in patients receiving pomalidomide and dexamethasone compared to dexamethasone alone. 

The median number of cycles administered was 7, ranging from 1 to 41 cycles. The overall response rate was evaluable for all patients, revealing that 18% achieved complete or very good partial remission, while 38% attained partial remission. However, 44% of patients exhibited minor or no response to pomalidomide therapy.

Possible side effects of Pomalidomide include low blood cell counts, unusual tiredness or physical weakness, nausea, back pain, neuropathy, upper respiratory infection or pneumonia, constipation, diarrhea, fever, dizziness and confusion, and shortness of breath. 

Pomalidomide Capsules are available in 1 mg, 2 mg, 3 mg, and 4 mg. It is taken orally and is used in combination with low-dose dexamethasone.