Pomalidomide Shows Durable Benefit for Hereditary Hemorrhagic Telangiectasia | HemOnc Today

A promising new avenue for treatment is emerging for hereditary hemorrhagic telangiectasia (HHT), a genetic disorder causing abnormal blood vessel formation. Recent findings suggest pomalidomide, an oral medication, can provide durable control of nosebleeds – the most common and often debilitating symptom of HHT – offering a potential long-term therapeutic option for some patients. Alongside this, researchers have validated a new quality-of-life scale designed to better assess the impact of HHT and compare the effectiveness of different treatments.

Understanding Hereditary Hemorrhagic Telangiectasia

HHT, also known as Osler-Weber-Rendu Syndrome, is the second most common inherited bleeding disorder, trailing only von Willebrand disease in prevalence. It affects approximately 1 in 5,000 people worldwide, though an estimated 80% of those affected remain undiagnosed, according to patient advocacy group Cure HHT. Cure HHT emphasizes the importance of raising awareness and improving access to care for those living with this often-underrecognized condition.

The disorder is characterized by the formation of abnormal connections between arteries and veins, bypassing the usual network of capillaries. These connections, along with fragile capillary beds (telangiectasias) often found in the nose and gastrointestinal tract, are prone to rupture, and bleeding. While telangiectasias can appear as small red or purple spots on the skin or inside the mouth, the most significant symptom for many is recurrent nosebleeds. Other complications can include gastrointestinal bleeding, iron deficiency anemia, and, in more severe cases, pulmonary or neurological issues.

Pomalidomide Shows Promise in Controlling Nosebleeds

The PATH-HHT trial, a randomized, placebo-controlled study, investigated the efficacy of pomalidomide (Pomalyst, Bristol Myers Squibb) in managing HHT symptoms. The trial involved 144 patients with moderate to severe nosebleeds, as measured by an Epistaxis Severity Score of 5 at the study’s outset. Participants were assigned to receive either pomalidomide (4 mg daily) or a placebo. Initial results published in Blood Advances demonstrated a statistically significant reduction in Epistaxis Severity Score in the pomalidomide group compared to the placebo group.

Follow-up data from the ATLAS study, which included 62 patients who continued pomalidomide treatment after the initial trial, showed sustained improvements. The mean Epistaxis Severity Score decreased from 5.55 at baseline to 2.8 after 12 months of treatment (P < .0001). A substantial majority of patients (90%) experienced an improvement of at least 0.71 points, and over half (55%) saw an improvement of 2.13 points or more – a level considered clinically meaningful.

However, pomalidomide’s effectiveness for gastrointestinal bleeding was less pronounced. Approximately two-thirds of patients with active GI bleeding discontinued treatment, either due to insufficient improvement or adverse events.

Navigating Potential Side Effects

While pomalidomide demonstrated efficacy, researchers noted potential side effects. The most common adverse event requiring dose reduction was neutropenia (low white blood cell count), occurring in about half of the patients. However, dose adjustments – typically to 2 mg or 3 mg daily – often allowed patients to continue benefiting from the medication. Other reported side effects included constipation and, less frequently, serious infections and venous thromboembolism.

Keith McCrae, MD, a hematologist at Cleveland Clinic, emphasized the importance of careful monitoring for neutropenia and the manageability of other side effects. “I think the drug is quite safe – particularly given most patients are able to respond to lower doses,” he stated.

A New Tool for Assessing Quality of Life

Recognizing the significant impact HHT can have on patients’ lives, researchers developed the HHT-specific quality-of-life (HHT-QoL) scale. This four-item scale assesses the impact of HHT on physical, social, personal, and operate-related aspects of life. Validation studies have shown the scale to be reliable and sensitive to changes in patients’ well-being. The HHT-QoL scale will be instrumental in future clinical trials, allowing researchers to compare the overall effects of different therapies and determine which treatments are most appropriate for individual patients.

The Path Forward: Ongoing Research and Personalized Treatment

Several clinical trials are currently underway or planned to evaluate various therapies for HHT. The availability of a validated quality-of-life scale will be crucial for comparing the effectiveness of these interventions. Dr. McCrae believes that the future of HHT treatment lies in personalized approaches, taking into account the specific manifestations of the disease in each patient and the practical considerations of treatment options.

“The phenotype of the disease and the practical aspects of treatment are very important factors,” Dr. McCrae explained. “For example, bevacizumab – another treatment option for HHT – may be more effective for GI bleeding, but requires intravenous infusion. A patient in a rural area might prefer oral pomalidomide.”

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As research continues and new treatments emerge, the outlook for individuals with HHT is becoming increasingly optimistic. The combination of targeted therapies like pomalidomide and tools for assessing quality of life promises to improve the lives of those affected by this challenging genetic disorder. Patients are encouraged to discuss treatment options and participate in clinical trials with their healthcare providers.