Pericarditis and Cardiac Tamponade in Patients Treated with First and Second Generation Bruton Tyrosine Kinase Inhibitors: An Underappreciated Risk.

Introduction: The introduction of Bruton's tyrosine kinase (BTK) inhibitors significantly improved the management of chronic lymphocytic leukemia (CLL). However, BTK carry the risk of cardiotoxicity, which is not only limited to atrial fibrillation. Case Reports. We report three cases of patients on BTK inhibitors who developed acute pericarditis and cardiac tamponade. We report the first patient who developed this complication on treatment with zanubrutinib. This patient's treatment was changed to zanubrutinib due to atrial fibrillation. Shortly after cardioversion, he developed cardiac tamponade and shock. He underwent pericardiocentesis, received treatment for acute pericarditis with steroids and colchicine, and made a full recovery. We also report two further cases, both involving patients treated with ibrutinib. These patients also developed acute pericarditis and cardiac tamponade and required pericardiocentesis. All three patients discontinued BTK therapy following the events. Conclusions: These three cases highlight the rare but potentially life-threatening risk of cardiac tamponade which can occur even with newer generations of BTK inhibitors. Haemato-oncologists should remain vigilant in patients who report dyspnea or who show sinus tachycardia on routine electrocardiography. Even in the absence of classical clinical signs of tamponade, patients require urgent evaluation with echocardiography and potentially emergency pericardiocentesis.

Venetoclax-based low intensity therapy in molecular failure of NPM1-mutated AML.

ABSTRACT: Molecular failure in NPM1-mutated acute myeloid leukemia (AML) inevitably progresses to frank relapse if untreated. Recently published small case series show that venetoclax combined with low-dose cytarabine or azacitidine can reduce or eliminate measurable residual disease (MRD). Here, we report on an international multicenter cohort of 79 patients treated for molecular failure with venetoclax combinations and report an overall molecular response (≥1-log reduction in MRD) in 66 patients (84%) and MRD negativity in 56 (71%). Eighteen of 79 patients (23%) required hospitalization, and no deaths were reported during treatment. Forty-one patients were bridged to allogeneic transplant with no further therapy, and 25 of 41 were MRD negative assessed by reverse transcription quantitative polymerase chain reaction before transplant. Overall survival (OS) for the whole cohort at 2 years was 67%, event-free survival (EFS) was 45%, and in responding patients, there was no difference in survival in those who received a transplant using time-dependent analysis. Presence of FLT3-ITD mutation was associated with a lower response rate (64 vs 91%; P < .01), worse OS (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.06-5.86; P = .036), and EFS (HR, 1.87; 95% CI, 1.06-3.28; P = .03). Eighteen of 35 patients who did not undergo transplant became MRD negative and stopped treatment after a median of 10 months, with 2-year molecular relapse free survival of 62% from the end of treatment. Venetoclax-based low intensive chemotherapy is a potentially effective treatment for molecular relapse in NPM1-mutated AML, either as a bridge to transplant or as definitive therapy.

Treating relapsed follicular lymphoma.

INTRODUCTION: Advanced follicular lymphoma (FL) remains an incurable disease, at least with conventional therapy. Despite the long remission and disease-free periods that can be currently achieved with treatment, the disease will ultimately relapse in most of the patients. Areas covered: This article reviews the current spectrum of therapies for patients with relapsed FL in the rituximab area. It will revisit current therapies, approaches to therapeutic decision making and novel agents under investigation. Expert commentary: At present, rituximab or second generation anti-CD20 antibodies either as single agent or in combination with chemotherapy, anti-CD20 maintenance therapy and stem cell transplant remain effective treatment options for relapsed patients. A plethora of new targeted agents and novel approaches such as immunotherapy are currently under investigation,thus the landscape is rapidly evolving. In this context, therapeutic decisions for individual patients in a disease which is increasingly becoming a chronic condition require a tailored approach integrating multiple clinical parameters with particular considerations of patients' preferences and quality of life.