Thalidomide offers short-term efficacy in HHT

MILAN—Results of a phase 2 trial suggest thalidomide can elicit solid—though not necessarily durable—responses among patients with hereditary hemorrhagic telangiectasia (HHT) suffering from severe, recurrent epistaxis.

All 29 evaluable patients responded to thalidomide, with 4 achieving a complete response.

Unfortunately, 11 patients relapsed at a median of 43 weeks. But re-treatment was possible for a few patients and did prompt additional responses.

“Our results strongly support the hypothesis that low-dose thalidomide is safe and very effective for the treatment of severe epistaxis in HHT patients who did not benefit from other available modalities of treatment,” said Rosangela Invernizzi, MD, of the University of Pavia in Italy.

“However, the effect of thalidomide is not permanent, and maintenance therapy may be required.”

Dr Invernizzi presented these discoveries at the 19th Congress of the European Hematology Association (EHA) as abstract S692.

She and her colleagues enrolled 31 HHT patients on this phase 2 study. The patients had a median age of 64 years (range, 44-84). Nine had grade 2 epistaxis, and 22 had grade 3.

Previous treatments included argon plasma coagulation (n=19), electrocautery (n=12), embolization (n=7), laser coagulation (n=2), septodermoplasty (n=2), and arterial ligation (n=1). Eighteen patients had received less than 10 units of red blood cells, and 13 had received 10 or more units.

For this study, patients received thalidomide at 50 mg a day for 4 weeks. Complete responders received 8 additional weeks of treatment at the same dosage. Partial responders received 16 additional weeks of treatment at the same dosage.

For non-responders, the dose was increased by 50 mg per day every 4 weeks until they attained a complete or partial response (with a maximum dose of 200 mg). If patients did not respond, they received 24 additional weeks of treatment. Thalidomide courses could be repeated 3 times at the most.

Response and relapse

The median follow-up was 67 weeks (range, 3-130 weeks). All of the 29 evaluable patients achieved a response, with 4 complete responses (14%) and 25 partial responses (86%).

Twenty-four patients responded within 4 weeks of treatment initiation, and 5 responded within 8 weeks. The minimum dose of thalidomide was 50 mg, and the maximum was 100 mg.

“A significant decrease of all epistaxis parameters—frequency [P=0.001], intensity [P<0.0001], and duration [P=0.0001]—was recorded,” Dr Invernizzi noted.

“As a consequence, thalidomide treatment significantly increased hemoglobin levels [P=0.02] and abolished or greatly decreased transfusion need [P=0.0003] and improved the quality of life.”

However, 11 patients relapsed at a median of 43 weeks. Patients who relapsed within 52 weeks of ending thalidomide could be treated again for 8 weeks at the same maximum dose employed during induction.

Four patients received re-treatment and achieved partial responses. One of these patients relapsed again at 13 weeks. But, for the other 3 patients, clinical improvement persisted at more than 17 weeks, more than 26 weeks, and more than 27 weeks.

Safety and tolerability

Dr Invernizzi said there were no noticeable side effects associated with re-treatment of relapsed patients.

The most common adverse events among all patients were gastrointestinal symptoms, such as constipation, vomiting, and dry mouth (n=15); drowsiness (n=9); and constitutional symptoms, such as asthenia, malaise, and peripheral edema (n=7).

There were 2 patients with psychiatric symptoms (confusion, depression) and 2 patients with thyroid dysfunction.

There was 1 cardiovascular event, (bradycardia, heart failure), 1 patient with low hematologic counts, 1 patient with neurologic symptoms (peripheral neuropathy, dizziness, tremor), 1 dermatologic event (toxic cutaneous rashes, skin dryness), and 1 infection.

MILAN—Results of a phase 2 trial suggest thalidomide can elicit solid—though not necessarily durable—responses among patients with hereditary hemorrhagic telangiectasia (HHT) suffering from severe, recurrent epistaxis.

All 29 evaluable patients responded to thalidomide, with 4 achieving a complete response.

Unfortunately, 11 patients relapsed at a median of 43 weeks. But re-treatment was possible for a few patients and did prompt additional responses.

“Our results strongly support the hypothesis that low-dose thalidomide is safe and very effective for the treatment of severe epistaxis in HHT patients who did not benefit from other available modalities of treatment,” said Rosangela Invernizzi, MD, of the University of Pavia in Italy.

“However, the effect of thalidomide is not permanent, and maintenance therapy may be required.”

Dr Invernizzi presented these discoveries at the 19th Congress of the European Hematology Association (EHA) as abstract S692.

She and her colleagues enrolled 31 HHT patients on this phase 2 study. The patients had a median age of 64 years (range, 44-84). Nine had grade 2 epistaxis, and 22 had grade 3.

Previous treatments included argon plasma coagulation (n=19), electrocautery (n=12), embolization (n=7), laser coagulation (n=2), septodermoplasty (n=2), and arterial ligation (n=1). Eighteen patients had received less than 10 units of red blood cells, and 13 had received 10 or more units.

For this study, patients received thalidomide at 50 mg a day for 4 weeks. Complete responders received 8 additional weeks of treatment at the same dosage. Partial responders received 16 additional weeks of treatment at the same dosage.

For non-responders, the dose was increased by 50 mg per day every 4 weeks until they attained a complete or partial response (with a maximum dose of 200 mg). If patients did not respond, they received 24 additional weeks of treatment. Thalidomide courses could be repeated 3 times at the most.

Response and relapse

The median follow-up was 67 weeks (range, 3-130 weeks). All of the 29 evaluable patients achieved a response, with 4 complete responses (14%) and 25 partial responses (86%).

Twenty-four patients responded within 4 weeks of treatment initiation, and 5 responded within 8 weeks. The minimum dose of thalidomide was 50 mg, and the maximum was 100 mg.

“A significant decrease of all epistaxis parameters—frequency [P=0.001], intensity [P<0.0001], and duration [P=0.0001]—was recorded,” Dr Invernizzi noted.

“As a consequence, thalidomide treatment significantly increased hemoglobin levels [P=0.02] and abolished or greatly decreased transfusion need [P=0.0003] and improved the quality of life.”

However, 11 patients relapsed at a median of 43 weeks. Patients who relapsed within 52 weeks of ending thalidomide could be treated again for 8 weeks at the same maximum dose employed during induction.

Four patients received re-treatment and achieved partial responses. One of these patients relapsed again at 13 weeks. But, for the other 3 patients, clinical improvement persisted at more than 17 weeks, more than 26 weeks, and more than 27 weeks.

Safety and tolerability

Dr Invernizzi said there were no noticeable side effects associated with re-treatment of relapsed patients.

The most common adverse events among all patients were gastrointestinal symptoms, such as constipation, vomiting, and dry mouth (n=15); drowsiness (n=9); and constitutional symptoms, such as asthenia, malaise, and peripheral edema (n=7).

There were 2 patients with psychiatric symptoms (confusion, depression) and 2 patients with thyroid dysfunction.

There was 1 cardiovascular event, (bradycardia, heart failure), 1 patient with low hematologic counts, 1 patient with neurologic symptoms (peripheral neuropathy, dizziness, tremor), 1 dermatologic event (toxic cutaneous rashes, skin dryness), and 1 infection.

MILAN—Results of a phase 2 trial suggest thalidomide can elicit solid—though not necessarily durable—responses among patients with hereditary hemorrhagic telangiectasia (HHT) suffering from severe, recurrent epistaxis.

All 29 evaluable patients responded to thalidomide, with 4 achieving a complete response.

Unfortunately, 11 patients relapsed at a median of 43 weeks. But re-treatment was possible for a few patients and did prompt additional responses.

“Our results strongly support the hypothesis that low-dose thalidomide is safe and very effective for the treatment of severe epistaxis in HHT patients who did not benefit from other available modalities of treatment,” said Rosangela Invernizzi, MD, of the University of Pavia in Italy.

“However, the effect of thalidomide is not permanent, and maintenance therapy may be required.”

Dr Invernizzi presented these discoveries at the 19th Congress of the European Hematology Association (EHA) as abstract S692.

She and her colleagues enrolled 31 HHT patients on this phase 2 study. The patients had a median age of 64 years (range, 44-84). Nine had grade 2 epistaxis, and 22 had grade 3.

Previous treatments included argon plasma coagulation (n=19), electrocautery (n=12), embolization (n=7), laser coagulation (n=2), septodermoplasty (n=2), and arterial ligation (n=1). Eighteen patients had received less than 10 units of red blood cells, and 13 had received 10 or more units.

For this study, patients received thalidomide at 50 mg a day for 4 weeks. Complete responders received 8 additional weeks of treatment at the same dosage. Partial responders received 16 additional weeks of treatment at the same dosage.

For non-responders, the dose was increased by 50 mg per day every 4 weeks until they attained a complete or partial response (with a maximum dose of 200 mg). If patients did not respond, they received 24 additional weeks of treatment. Thalidomide courses could be repeated 3 times at the most.

Response and relapse

The median follow-up was 67 weeks (range, 3-130 weeks). All of the 29 evaluable patients achieved a response, with 4 complete responses (14%) and 25 partial responses (86%).

Twenty-four patients responded within 4 weeks of treatment initiation, and 5 responded within 8 weeks. The minimum dose of thalidomide was 50 mg, and the maximum was 100 mg.

“A significant decrease of all epistaxis parameters—frequency [P=0.001], intensity [P<0.0001], and duration [P=0.0001]—was recorded,” Dr Invernizzi noted.

“As a consequence, thalidomide treatment significantly increased hemoglobin levels [P=0.02] and abolished or greatly decreased transfusion need [P=0.0003] and improved the quality of life.”

However, 11 patients relapsed at a median of 43 weeks. Patients who relapsed within 52 weeks of ending thalidomide could be treated again for 8 weeks at the same maximum dose employed during induction.

Four patients received re-treatment and achieved partial responses. One of these patients relapsed again at 13 weeks. But, for the other 3 patients, clinical improvement persisted at more than 17 weeks, more than 26 weeks, and more than 27 weeks.

Safety and tolerability

Dr Invernizzi said there were no noticeable side effects associated with re-treatment of relapsed patients.

The most common adverse events among all patients were gastrointestinal symptoms, such as constipation, vomiting, and dry mouth (n=15); drowsiness (n=9); and constitutional symptoms, such as asthenia, malaise, and peripheral edema (n=7).

There were 2 patients with psychiatric symptoms (confusion, depression) and 2 patients with thyroid dysfunction.

There was 1 cardiovascular event, (bradycardia, heart failure), 1 patient with low hematologic counts, 1 patient with neurologic symptoms (peripheral neuropathy, dizziness, tremor), 1 dermatologic event (toxic cutaneous rashes, skin dryness), and 1 infection.