Incidence of major bleeding in patients with chronic lymphocytic leukemia receiving ibrutinib and therapeutic anticoagulation.

Increased rates of clinically significant bleeding have been reported with ibrutinib, however, limited data is available on the risk when given with concomitant therapeutic anticoagulation. We analyzed the incidence of major bleeding in 64 patient exposures that received ibrutinib with concomitant therapeutic anticoagulation. Major bleeding was observed in 5/64 (8%) patient exposures. The highest incidence was observed with rivaroxaban (3/17, 18%), followed by apixaban (2/35, 6%). No major bleeding events were seen with enoxaparin (n = 10). A total of 38% of patient exposures received a concomitant antiplatelet agent along with therapeutic anticoagulation. Among these patients, one (4%) experienced a fatal hemorrhage while taking ibrutinib, apixaban, and clopidogrel concomitantly. Our retrospective study observed a higher rate of major hemorrhage with combined DOAC with ibrutinib than historically reported with ibrutinib alone. This combination may be associated with increased risk of major bleeding and further prospective studies evaluating this risk are necessary.

An update on the efficacy of Venetoclax for chronic lymphocytic leukemia.

INTRODUCTION: The BCL2 inhibitor venetoclax has dramatically changed the treatment of chronic lymphocytic leukemia (CLL) and has introduced the concept of time-limited therapy with targeted agents. AREAS COVERED: This review discusses the mechanism of action of venetoclax, adverse effects, and the clinical data with this agent as identified by a selective search of clinical trials in the PubMed database. Venetoclax is FDA-approved with anti-CD20 monoclonal antibodies; however, research is ongoing evaluating its efficacy when given in combination with other agents, such as the Bruton's Tyrosine Kinase (BTK) inhibitors. EXPERT OPINION: Venetoclax-based therapy is an excellent treatment option for patients interested in time-limited therapy and can be offered in both the front-line and relapsed/refractory settings. Tumor lysis syndrome (TLS) risk evaluation, preventative measures, and strict monitoring should be conducted, while these patients ramp up to target dose. Venetoclax-based therapies produce deep and durable responses with patients often achieving undetectable measurable residual disease (uMRD). This has led to a discussion of MRD-driven, finite-duration treatment approaches, although longer term data is still needed. While many patients eventually lose uMRD status, re-treatment with venetoclax remains an area of interest with promising results. Mechanisms of resistance to venetoclax are being elucidated, and research is ongoing.

Incidence of adverse effects in patients receiving ponatinib with concomitant azole antifungals.

Ponatinib plus Hyper-CVAD yields a five-year overall survival of 73% in patients with Philadelphia-positive acute lymphoblastic leukemia. Ponatinib dose intensity is associated with increased incidence of adverse effects (AEs), including vascular events. Ponatinib combined with azole antifungals may further increase the risk of AEs due to increased ponatinib exposure. We reviewed 53 patients who received ponatinib with intensive (n = 39; 74%) or low-intensity chemotherapy (n = 14; 26%). Forty-eight patients (91%) received concomitant azole. Ponatinib was commonly initiated at 30 mg (n = 30; 57%) or 45 mg daily (n = 21; 40%). Twenty-six patients (49%) experienced at least one grade ≥3 AE possibly related to ponatinib; 19 (73%) were receiving a ponatinib dose equivalent ≥30mg and 58% >45mg. Eight patients (15%) experienced 10 vascular events, including 1 arterial event; 9 occurred on a ponatinib dose equivalent ≥30mg and 5 occurred while on an azole. Vascular events pose a clinical challenge with the risk potentially increasing with concomitant azoles.

Selecting the optimal BTK inhibitor therapy in CLL: rationale and practical considerations.

Bruton's tyrosine kinase (BTK) inhibitors have dramatically changed the treatment of newly diagnosed and relapsed/refractory chronic lymphocytic leukemia (CLL). Ibrutinib, acalabrutinib, and zanubrutinib are Food and Drug Administration (FDA)-approved BTK inhibitors that have all demonstrated progression-free survival (PFS) benefit compared with chemoimmunotherapy. The efficacy of these agents compared to one another is under study; however, current data suggest they provide similar efficacy. Selectivity for BTK confers different adverse effect profiles, and longer follow-up and real-world use have characterized side effects over time. The choice of BTK inhibitor is largely patient-specific, and this review aims to highlight the differences among the agents and guide the choice of BTK inhibitor in clinical practice.

Drug-Induced Hypertension: Focus on Mechanisms and Management.

PURPOSE OF REVIEW: This review is intended to briefly describe the primary mechanistic pathways by which several common drugs can increase blood pressure. We also propose potential management strategies based on the underlying mechanisms responsible for the blood pressure elevation. RECENT FINDINGS: As hypertension is a significant risk factor for cardiovascular events, healthcare providers must evaluate patients' concomitant medications that may contribute to elevations in blood pressure. The presence of these medications, if not properly addressed, can lead to consequences such as an inadvertent diagnosis of hypertension, as well as the potential need for unnecessary intensification of antihypertensive regimens in those already treated. Blood pressure elevation is an unfortunate by-product of multiple medications. The substances discussed in this review can elicit significant and persistent elevations in blood pressure, and health care providers must first evaluate whether the drug is necessary. If one exists, it is best to select a similar agent with lower risk of increasing blood pressure; if unavoidable, then clinicians should select an appropriate management strategy to compensate for the rise in blood pressure.