Effect of systemic bevacizumab in severe hereditary hemorrhagic telangiectasia associated with bleeding

Abstract

former cohort suggests that prolonged ibrutinib exposure increases the propensity for AF over time, or that these patients were at a higher risk of developing AF due to advancing age and exposure to other AF related morbidities such as hypertension, prolonged disease exposure, and effects of prior therapeutics. Cardiac amyloidosis is highly associated with arrhythmias and may have contributed to AF in one patient. The findings nonetheless continue to support an increased risk of AF for WM patients on ibrutinib therapy. The causal mechanism for ibrutinib related AF remains under investigation, though inhibition of cardiac PI3K-Akt signaling has been hypothesized [6].Despite the increased risk of ibrutinib associated AF, the overall efficacy and safety data of this agent in WM continues to supports its use. Many adverse events common to other WM therapies are absent with ibrutinib, including uninvolved immunoglobulin depletion, peripheral neuropathy, myelosuppression, disease transformation, and increased risk of secondary cancers, including treatment related myelodysplasia and acute myeloid leukemia [1]. Moreover, a prior history of AF does not appear to prohibit treatment with ibrutinib, as 11 of 12 patients (92%) with an AF event continued on ibrutinib following cardiology intervention. A baseline electrocardiogram appears warranted as to screen for arrhythmias prior to ibrutinib initiation. In summary, a higher incidence of AF is associated with the use of ibrutinib in WM patients than previously reported, with a shorter time to AF event observed in patients with versus without a prior history of AF. Nearly all patients who developed AF were able to continue ibrutinib following cardiological intervention and/or ibrutinib dose reduction.

Does severe bleeding in HHT patients respond to intravenous bevacizumab? Review of the literature and case series

“…In total, 141 of 162 patients (87%) benefited from systemic IV bevacizumab treatment with reduced bleeding. Bleeding (epistaxis and/or GI bleeding) was the treatment indication in 106 patients (23,(26)(27)(28)(29)(30) , of whom 92 (87 %) had a positive effect of treatment with reduced bleeding, reduced transfusion needs, and/or increased levels of hemoglobin. Fifty-six patients from three studies (17,29,31) were primarily treated with systemic IV bevacizumab due to symptomatic hepatic involvement.…”

“…The repeated search in September 2018 resulted in one extra case report (25) and one extra case series (26) . Characteristics of the eight case series (17,23,(26)(27)(28)(29)(30)(31) and the 33 case reports (25, included in the present study are summarized in Table 3 and Table 4, respectively, including study type, number of patients, gender,…”

Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber Disease

“…Furthermore, as in our case, authors described an extremely quick and long-term response, as well as the occurrence of early relapse following drug discontinuation [19][20][21]. Epperla et al [21] published a case series comprising 5 ROW patients (4 with epistaxis and only 1 with gastrointestinal hemorrhage) who have reduced their PRBC consumption by 51-100% and their total number of emergency department visits and hospitalizations by 78%. Of note, hypertension and proteinuria were observed in 2 and 1 of those patients, respectively, during the follow-up period [21].…”

“…In fact, patients who were refractory to several other medical and endoscopic approaches, and whose transfusion requirements ranged from 1 unit of PRBC every week to about 300 units in a year, all were reported to have developed a significant decrease in bleeding episodes and transfusion needs [19][20][21][22][23]. Furthermore, as in our case, authors described an extremely quick and long-term response, as well as the occurrence of early relapse following drug discontinuation [19][20][21]. Epperla et al [21] published a case series comprising 5 ROW patients (4 with epistaxis and only 1 with gastrointestinal hemorrhage) who have reduced their PRBC consumption by 51-100% and their total number of emergency department visits and hospitalizations by 78%.…”

“…Epperla et al [21] published a case series comprising 5 ROW patients (4 with epistaxis and only 1 with gastrointestinal hemorrhage) who have reduced their PRBC consumption by 51-100% and their total number of emergency department visits and hospitalizations by 78%. Of note, hypertension and proteinuria were observed in 2 and 1 of those patients, respectively, during the follow-up period [21]. The optimal dose and regimen for this agent are not fully established yet.…”