Findings from a retrospective study being presented at the 2019 ASH Annual Meeting support the use of bevacizumab to treat chronic bleeding and anemia in patients with hereditary hemorrhagic telangiectasia (HHT).
“Bevacizumab…is a potential targeted anti-angiogenic treatment in HHT, which has no FDA-approved therapy. Data for use of intravenous (IV) bevacizumab in HHT is currently limited to case reports and small single-center retrospective case series,” explained Hanny Al-Samkari, MD, Harvard Medical School, Boston, MA, and colleagues, who sought to fill this gap in literature.
Thus, they conducted a study to assess the safety and efficacy of systemic bevacizumab for the treatment of chronic bleeding and anemia in HHT using retrospective data for patients with HHT treated for at least 3 months with off-label systemic bevacizumab for chronic bleeding. These data included demographics, baseline HHT characteristics, epistaxis severity scores (ESS, a validated 10-point scale to evaluate epistaxis in HHT), and information about bevacizumab dosing, treatment-emergent adverse events (TEAEs), hemoglobin (Hb), red blood cell (RBC) transfusions, and IV iron infusions.
Using the paired t-test, Dr Al-Samkari et al compared the baseline Hb and ESS with post-bevacizumab values at 3, 6, 9, and 12 months. In addition, they used the Wilcoxon signed rank test to compare RBC transfusion and iron infusion requirements before and after bevacizumab therapy.
Overall, there were 140 patients with HHT treated with IV bevacizumab for chronic bleeding (median time frame, 23 months; median total infusions, 12). Patients were given bevacizumab 5 mg/kg every 2 weeks for the first 2 months, then received the drug monthly for 4 months. After this, patients were given maintenance dosed in accordance with the practices observed at their treatment centers.
Patients with anemia (Hb<11) at baseline (n=104) had an increase in mean Hb after starting bevacizumab, from 8.6 g/dL to 11.9 g/dL at 3 months (P<.0001) and up to 12.5 g/dL at 12 months (P<.0001).
Among patients for whom epistaxis was an indication for bevacizumab (n=119), the mean ESS went down with treatment from 6.8 at baseline to ≤3.5 during therapy (P<.0001). For the 81 patients who needed RBC transfusions before therapy, transfusion requirements dropped from a median of 8 units in the 6 months before therapy to a median of 0 units in the first 6 months post-therapy (P<.0001). Requirements for the 99 patients who needed iron infusions before initiating therapy also decreased from a median of 4 infusions to 2 (P<.0001).
“RBC transfusion and iron infusion requirements continued to improve with ongoing bevacizumab treatment and improvement occurred regardless of baseline bleeding severity,” Dr Al-Samkari and co-investigators said.
Notably, requirements for RBC transfusions and iron infusions dropped by 86% and 66%, respectively, with bevacizumab therapy from what they were pretreatment.
Findings also showed that bevacizumab was well-tolerated, with only 36% of patients having TEAEs possibly related to the drug. There were no reports of venous thromboembolism, and only five (4%) patients had to discontinue bevacizumab therapy because of TEAEs. Lack of efficacy led to discontinuation of the drug in only three (2%) patients.
“We present results of IV bevacizumab treatment of chronic bleeding and anemia in a large cohort of 140 HHT patients, demonstrating that bevacizumab was highly effective, with an improvement in mean Hb of 3.9 g/dL, dramatic reduction in ESS, and decrease in RBC transfusion and iron infusion requirements by 86% and 66%, respectively,” shared Dr Al-Samkari and colleagues.
“Effectiveness was maintained over time. Safety analysis included a total of 194 patient-years of IV bevacizumab administration to HHT patients and had low TEAE rates with only 4% discontinuing treatment due to TEAEs,” they concluded. —Hina Porcelli