The findings of a study led by researchers from Hadassah’s Clinical Immunology and Allergy Unit promise treatment for the unbearable itching phenomenon that accompanies tens of thousands of cancer patients worldwide. “Itching manages patients’ day while causing suffering and is accompanied by severe impairment of quality of life,” emphasizes Prof. Yuval Tal, Director of the Clinical Immunology Unit. “The drug given to patients is recognized as a safe treatment and has shown impressive efficacy by eliminating itching after just a few doses.”

 

Prof. Yuval Tal

In addition to coping with the difficulties of the disease, pain, and treatments, cancer patients may experience complex and unbearable coping with a well-known phenomenon of massive itching in all parts of the body, which burdens their activities of daily life, impairs their quality of life and accompanies them for many months.

In a study conducted at Hadassah Medical Center, researchers led by Prof. Yuval Tal succeeded in finding an effective treatment to eradicate itching. The study aroused great international interest after it was presented at the annual conference of the European Society of Clinical Immunology and Allergy in Hamburg and published in the Journal of Allergy and Clinical Immunology: Global. “Oncological itching is a phenomenon suffered by tens of thousands of cancer patients worldwide,” explains Prof. Tal. “This is an intolerable situation for patients, which sometimes precedes the diagnosis of the malignant disease and in other cases is due to side effects of the treatment itself. “The cancer cells secrete various proteins, cytokines, which cause significant and treatment resistant itching, while the main ones inducing itching are cytokines IL-4, IL-13, and IL-31.

Patients describe diffuse and incessant itching that significantly impairs their daily functioning and routine, even though no visual findings, rashes, or changes in skin color appear on the body’s surface. The continuous act of itching leads to self-injury even during sleep.” This resistant itch, emphasizes Prof. Tal, “is itching that does not respond to conventional treatments such as steroids, phototherapy, antihistamines, etc. Itching impairs quality of life so badly that the terrible key phrase of these patients is many times: “I’d rather die of cancer and stop itching. The phenomenon is more prevalent in patients suffering from hematologic malignancies. Still, it exists in cancer patients of all types. Since there are no signs on the skin’s surface, some are suspected of suffering from psychogenic itching and are sent for various tests to understand the cause. The treatments sometimes include high dose steroids that not only do not sufficiently relieve the itching but cause a wide range of side effects that affect many systems in the patient’s body, including the skin.

“The itching,” emphasizes Prof. Tal, “may accompany patients regardless of treatment, meaning that it is not a side effect of one drug or another, although even when it is caused by drug therapy, the results of this preliminary study indicate that the treatment is still highly effective.” In the clinical study led by Prof. Tal and Dr. Aviv Talmon, a senior physician in Hadassah’s Clinical Immunology Unit, in close collaboration with Prof. Michal Lotem of the Oncology Division and Dr. Shlomo Elias of the Hematology Division, the efficacy of a biological treatment approved for the treatment of other medical conditions was examined based on the hypothesis of the molecular mechanism that causes this condition. In practice, the effectiveness of this treatment has been demonstrated in three patients with different malignancies and anti-cancer therapies, as described in an article in JACI-global, which also reveals the hypothesized mechanism. “The study examined three different patients with different malignancies, all three of whom had itching at a level of 9-10 out of 10 on the itching scale, which is, by definition, the worst itching that can be described,” explains Prof. Tal.

Dr. Aviv Talmon

The three patients received the drug Dupixent (dupilumab), which is known to block the effect of the immune system’s “allergic arm” proteins, IL-4 and IL-13, and decreases the production of cytokine-IL-31, commonly known as the “itch cytokine.” These proteins directly affect the nerve cells that transmit the itching message to the brain. Therefore, the administration of dupilumab prevents nerve transmission and, thus, the itching sensation.

The drug is intended and approved for treating severe asthma patients and patients with atopic dermatitis from the age of 6 in Israel and six months in the United States and was submitted to the basket this year for additional indications. This is the first and only publication in which the effectiveness of dupilumab treatment has been tested for a target population of cancer patients suffering from itching resulting from malignancy or treatments for this disease. In all three patients, a clinically significant response was achieved after receiving the first injection, and all three showed a very impressive response after a third injection to the point where the itching disappeared completely. Two of the patients have since received the treatment regularly, and the drug’s effect continues with the same effectiveness,” concludes Prof. Tal. The third patient, a 32-year-old young man, did not receive approval to continue the medication, and the itching returned with the same intensity after discontinuing treatment. The unit’s doctors are working to obtain the drug for the patient under compassionate use.

“In this preliminary work, we demonstrated that dupilumab treatment is safe and effective in patients with severe and resistant itching associated with malignancies or treatment. A prospective clinical study aimed at treating secondary itching for malignant disease and its treatments has been conducted over the past year, led by Dr. Aviv Talmon and Dr. Eyal Ben-Dori and assisted by the staff of Hadassah’s Clinical Immunology Unit. In this study, we are trying to show a large cohort of patients the efficacy and safety of dupilumab and uncover the proposed molecular mechanism. Dupilumab is given to all study participants, and we call on patients from all over the country suffering from resistant oncological itching to participate in the study. We will do everything possible to help any patient who contacts us.”