According to a recent article, the trial studying the success of CLR 131 to treat Waldenstrom’s macroglobulinemia has shown promising results, allowing it to continue.

Waldenstrom Macroglobulinemia (WM)

Waldenstrom macroglobulinemia (WM) is a type of lymphoma, i.e. a cancer that starts in the immune system blood cells known as lymphocytes. WM starts in a type of white blood cell called a B lymphocyte, which helps the body fight off infections and disease. In WM, the cancerous cells create large amounts (a macroglobulin) of an abnormal version of a protein antibody called immunoglobulin M (IgM). As the cancer cells increase, they build up and crowd out normal red blood cells, making blood thicker than normal (called hyperviscosity). WM is rare. It accounts for approximately 1-2% of all blood cancers. Worldwide, there are approximately five cases of WM per one million persons each year. It most commonly affects white populations and is almost twice as common in males than females. The chance of developing WM goes up with age, as most cases are diagnosed in people in their mid-60s.

Symptoms:

Many people have no symptoms at all, and WM is ultimately detected through a routine blood test. But as abnormal B cells fill up bone marrow or collect in the lymph nodes, spleen, or other body parts, symptoms become more common. These most commonly include:

• Tiredness, weakness, and breathlessness due to low red blood cell counts (anemia)
• Infections due to low white blood cell counts
• Bruising or bleeding caused by low platelet counts
• Nosebleeds, blurring or loss of vision, dizziness/headaches, poor concentration, or shortness of breath due to hyperviscosity causing blood to flow slowly and/or at higher pressure
• Enlarged lymph nodes of the spleen
• Abdominal swelling and diarrhea
• Raised pink or flesh-colored lesions on the skin
• Unexplained weight loss

Treatment:

Often the first approach to treatment for a slowly-progressing cancer such as WM is “watching and waiting”— your doctor will monitor you closely and begin treatment when progression makes it necessary. After this threshold has been passed, treatments include:

• Chemotherapy
• Targeted drugs
  • Imbruvica
  • Bruton’s Tyrosine Kinase (BTK)-Inhibitor, SNS-062, from Sunesis Pharmaceuticals, Inc., which has just been dosed in the start of a Phase 1b/2 expansion trial
• Biological therapies (immunotherapy)
• Plasma exchange (called plasmapheresis)
• Stem cell transplant
• Radiation

The Trial

The trial is a phase 2 CLOVER-1 clinical trial. It is studying if CLR 131 (iopofosine) will work as a treatment option for patients diagnosed with relapsed or refractory Waldenstrom’s macroglobulinemia. The pharmaceutical company Cellectar Biosciences is responsible for the creation of the drug.

The positive results from the trial so far means it will go ahead and enlist 50 patients diagnosed with Waldenstrom’s macroglobulinemia. The patients will be given up to four doses of CLR 131 in two treatment cycles.

Major response rate is the trial’s main goal. This has been defined as the immunoglobin (IgM) levels in patients reducing a minimum of a 50%. These are the antibodies that are produced excessively in patients with WM. Furthermore, the trial has goals of duration of response and progression-free survival.

The FDA has approved the trial based on a 20% major response rate hurdle being the main endpoint of the study. After a presentation at ASCO 2021, where 5 patients had an 83.3% major response rate, and one other patient even had a complete response, it inspired researchers to continue their research into this treatment option.