Electrocardiographic Changes Associated With Ibrutinib Exposure.

Although ibrutinib-associated atrial and ventricular arrhythmias have been well described, there is little information about ibrutinib's effects on other electrocardiographic parameters, particularly the QT interval. Using our database of 137 patients treated with ibrutinib, we retrospectively identified 21 patients in whom an electrocardiogram (ECG) was obtained both prior to and after ibrutinib exposure. All traditional ECG parameters as well as QT dispersion were manually measured by an electrophysiologist. Compared to baseline ECGs, post ibrutinib ECGs demonstrated QT interval shortening from 386 ms to 356 ms (P = .007), corrected QT interval shortening using Bazett's formula from 446 ms to 437 ms (P = .04), and corrected QT interval shortening using Fridericia's formula from 425 ms to 407 ms (P = .003). QT dispersion also increased post ibrutinib exposure compared to baseline (39.8 ms vs 57.3 ms, P = .002). There was no significant change in other ECG parameters. In conclusion, both the absolute and corrected QT intervals significantly shortened after ibrutinib exposure, while there was a significant increase in QT dispersion. These findings may point to a common underlying electrophysiologic mechanism of ibrutinib-associated arrhythmias.

Chronic Lymphocytic Leukemia in the Elderly, Which Investigations Are Necessary: A Map for the Practicing Oncologist.

BACKGROUND: Chronic lymphocytic leukemia (CLL), the most prevalent leukemia in the Western world, is predominantly a disease of older individuals who also have other comorbidities as well as declining organ and bone marrow reserve. Although chemoimmunotherapy is the frontline therapy for fit CLL patients who can tolerate the therapy, many elderly patients cannot tolerate such intense therapy. METHODS: The authors first reviewed the most recent findings concerning CLL cytogenetics, molecular biology, and prognostic models. They then surveyed recent and ongoing trials of novel CLL agents and strategies, with a focus on those most relevant to elderly patients. RESULTS: Novel therapies, revised staging procedures, and careful assessment of individual patients' frailty and functional status will allow clinicians to provide optimal care management for older CLL patients. CONCLUSION: Therapy for the elderly CLL population must be tailored to each patient's fitness level and comorbid conditions, with special consideration for the potential quality-of-life impacts of various treatment recommendations.

Recurrent Systemic Anaplastic Lymphoma Kinase-Negative Anaplastic Large Cell Lymphoma Presenting as a Breast Implant-Associated Lesion.

A woman aged 48 years presented with fevers, chills, weight loss, and night sweats. She had significant lymphadenopathy of the left neck as well as the left axilla. Her history was significant for bilateral breast augmentation with textured silicone implants more than 25 years ago. Excisional biopsy of a cervical lymph node revealed large, atypical cells positive for CD4 and CD30 and negative for Epstein-Barr virus-encoded ribonucleic acid, CD2, CD3, CD5, CD7, CD8, CD15, CD20, pan-keratin, S100, anaplastic lymphoma kinase (ALK), and paired box 5. These findings were consistent with Ann Arbor stage IIIB ALK-anaplastic large cell lymphoma (ALCL). The patient was started on 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone. She initially had no signs or symptoms of breast involvement; however, after developing seroma during the clinical course, the patient underwent capsulectomy and removal of the intact, textured silicone implants. Pathological evaluation demonstrated ALK-ALCL in the left breast capsule with cells displaying a significant degree of pleomorphism with binucleated forms and numerous mitoses. Fluorescence in situ hybridization confirmed the tumor was negative for t(2;5). She presented 8 weeks later showing evidence of recurrent systemic disease.

Ciprofloxacin Versus Levofloxacin Prophylaxis in Hematopoietic Stem Cell Transplantation: A Randomized Trial.

OBJECTIVES: We aimed to assess whether there is a difference between ciprofloxacin and levofloxacin as prophylaxis in hematopoietic stem cell transplant (SCT) recipients. METHODS: This is a prospective, randomized trial in patients receiving SCT at Henry Ford Health in the United States of America. We randomly assigned patients (1:1) to receive ciprofloxacin or levofloxacin. The primary outcome was incidence of bloodstream bacterial infections (BSI) up to day 60 after SCT. RESULTS: Between June 4, 2018, and May 23, 2022, we randomly assigned 308 consecutive patients to receive ciprofloxacin (154 patients) or levofloxacin (154 patients). BSI was similar in both the ciprofloxacin and levofloxacin groups (18 [11.7%] vs 18 [11.7%]). Pneumonia was more frequent in the ciprofloxacin group compared to the levofloxacin group (18 [18%] vs 7 [23%]; relative risk 2.57, 95% CI 1.11-5.98; p = 0.028). There were no differences in neutrophil engraftment, fever, Clostridium difficile infection, relapse incidence, overall survival, non-relapse mortality, length of stay post-SCT, or intensive care unit admission. CONCLUSIONS: Although both prophylaxis regimens demonstrated the same efficacy in SCT recipients, levofloxacin prophylaxis led to less pneumonia in the first 60 days post-SCT. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, NCT03850379.

Neuropsychiatric disorders in adults undergoing chimeric antigen receptor T cells therapy for aggressive lymphomas and acute lymphoblastic leukemia.

Objective: To evaluate risk factors for neuropsychiatric disorders (NPD) in recipients of CART therapy. Methods: Patients ≥ 18 years with acute lymphoblastic leukemia (ALL), and aggressive B-cell lymphomas who received CART in 2018 were evaluated. Patients with and without NPD were compared. Results: NPD was diagnosed in 31.2% of patients. Compared to patients without NPD, patients with NPD were likely to be females (P = 0.035) and have ALL (P = 0.039). NPD was significantly associated with female gender (OR = 2.03) and diagnosis of ALL (OR = 2.76). No association between NPD and outcomes. Conclusions: Female gender and ALL were risk factors for NPD.

A Case of Right Ventricular Failure Secondary to Acute Chest Syndrome Managed With Early Red Cell Exchange Transfusion.

Patients with sickle cell disease are at risk of vaso-occlusive crises including acute chest syndrome (ACS) and pulmonary hypertension. ACS is a life-threatening complication of sickle cell disease and is associated with increased morbidity and mortality. It is known that pulmonary pressures increase during episodes of acute chest syndrome and may lead to acute right ventricular failure leading to increased morbidity and mortality. Given the paucity of randomized controlled trials, the management of ACS and pulmonary hypertension in the setting of a sickle cell crisis largely relies on expert opinion. We present a case of acute chest syndrome complicated by acute right ventricular failure that was managed with prompt red cell exchange transfusion with favorable clinical outcomes.

Demographic differences among patients treated with chimeric antigen receptor T-cell therapy in the United States.

BACKGROUND: It is not clear if all Americans have benefitted equally from the availability of chimeric antigen receptor T-cell (CART) therapy. We aimed to evaluate if demographic differences existed among adult patients who received CART therapy and to assess predictors of CART treatment outcomes. METHODS: Records of patients ≥18 years who received CART therapy for non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and multiple myeloma in 2018 were evaluated in the National Inpatient Sample. Acute complications and inhospital mortality were compared between two groups of CART recipients: Whites and non-Whites. Logistic regression analysis was used to evaluate the association between sociodemographic factors and inhospital mortality. RESULTS: Of 1275 CART recipients that met inclusion criteria, there were 40.4% of females, 66.9% of Whites, Blacks (4.2%), Hispanics (13.3%), Asians or Pacific Islanders (4.2%), and Native Americans (1.3%). Up to 96.8% of CART procedures were performed in urban teaching hospitals, and 85.3% of CART recipients lived in metropolitan counties. Non-Whites, compared to Whites, were younger at the time of CART therapy (p < 0.001). The inhospital mortality rate was higher in non-Whites, though not statistically significant (5.4% vs. 4.4%, p = 0.764). There were no differences in length of hospital stay, hospital charges, or rates of acute toxicities between the two race groups. We found no association between race and treatment outcomes. Gender, neurotoxicity, and Charlson Comorbidity Index were significant predictors of inhospital mortality. CONCLUSIONS: CART therapy recipients in the United States were more likely to be Whites and more likely to be residents of metropolitan areas. These observed demographic differences were not associated with treatment outcomes or inhospital mortalities.

Association between ibrutinib treatment and hypertension.

BACKGROUND: Ibrutinib is a tyrosine kinase inhibitor most commonly associated with atrial fibrillation. However, additional cardiotoxicities have been identified, including accelerated hypertension. The incidence and risk factors of new or worsening hypertension following ibrutinib treatment are not as well known. METHODS: We conducted a retrospective study of 144 patients diagnosed with B cell malignancies treated with ibrutinib (n=93) versus conventional chemoimmunotherapy (n=51) and evaluated their effects on blood pressure at 1, 2, 3 and 6 months after treatment initiation. Descriptive statistics were used to compare baseline characteristics for each treatment group. Fisher's exact test was used to identify covariates significantly associated with the development of hypertension. Repeated measures analyses were conducted to analyse longitudinal blood pressure changes. RESULTS: Both treatments had similar prevalence of baseline hypertension at 63.4% and 66.7%, respectively. There were no differences between treatments by age, sex and baseline cardiac comorbidities. Both systolic and diastolic blood pressure significantly increased over time with ibrutinib compared with baseline, whereas conventional chemoimmunotherapy was not associated with significant changes in blood pressure. Baseline hypertensive status did not affect the degree of blood pressure change over time. A significant increase in systolic blood pressure (defined as more than 10 mm Hg) was noted for ibrutinib (36.6%) compared with conventional chemoimmunotherapy (7.9%) at 1 month after treatment initiation. Despite being hypertensive at follow-up, 61.2% of patients who were treated with ibrutinib did not receive adequate blood pressure management (increase or addition of blood pressure medications). Within the ibrutinib group, of patients who developed more than 20 mm Hg increase in systolic blood pressure, only 52.9% had hypertension management changes. CONCLUSIONS: Ibrutinib is associated with the development of hypertension and worsening of blood pressure. Cardiologists and oncologists must be aware of this cardiotoxicity to allow timely management of blood pressure elevations.

Disparities in Utilization of Autologous Stem Cell Transplantation as Consolidative Therapy for Multiple Myeloma: A Single Institution Retrospective Review.

BACKGROUND: Most guidelines recommend induction therapy followed by autologous hematopoietic cell transplantation. A Surveillance, Epidemiology, and End Results-Medicare database analysis from 2000 to 2011 noted a lower use of HCT and bortezomib among Black patients, despite adjusting for care barriers, and this practice was associated with a poorer outcome. The goal of this study was to evaluate patterns of acceptance of HCT as consolidative therapy for MM. METHODS: Cox proportional hazards model was used to investigate the association between the survival time of the patients (overall survival) and age of the diagnosis, race, socioeconomic status, disease cytogenetic, and initial induction regimens. A total of 194 patients with a confirmed diagnosis of MM who were referred for HCT between January 1, 2009, and June 30, 2019, were included in this study. Patients who received autologous stem cell transplant for relapsed MM were excluded. RESULTS: We found that income category was not significantly associated with overall survival, time to transplant or transplant-/relapse-related mortality. High-risk cytogenetic was significantly associated with shorter overall survival, higher transplant-related mortality and relapse-related mortality (P < .002). The use of aggressive induction choices was associated with poorer transplant outcomes (P = .02). Time to transplant tended to be shorter in African American compared with other ethnic groups (P = .07). CONCLUSION: There was no significant difference in the use rate of the HCT between Caucasians and AA patients with MM. Further comparative studies of MM induction therapy and access to clinical trials in African Americans and other racial minorities are warranted.

Rates and Risk of Atrial Arrhythmias in Patients Treated With Ibrutinib Compared With Cytotoxic Chemotherapy.

There is increasing evidence that rates of atrial arrhythmias (AA), specifically atrial fibrillation and flutter are elevated in patients treated with the tyrosine kinase inhibitor, ibrutinib; however, the exact risk of ibrutinib-associated AA is not definitively established. We conducted a retrospective study of 137 patients diagnosed with B-cell malignancies treated with ibrutinib compared with 106 patients treated with chemotherapy for the same cancers in order to quantify the rates and risk of AA in a "real-world" sample of cancer patients. Fisher's exact test was used to evaluate for any statistically significant differences between groups. Logistic regression was used to generate odds ratios, adjusting for potential confounders. Incidence of AA was 14% (n = 17) in ibrutinib-treated patients compared with 3% (n = 3) in patients treated with chemotherapy (p = 0.009). Ibrutinib-treated patients were significantly older (mean age 67 vs 63 years, p = 0.003); however, there were no other significant differences in baseline characteristics. Ibrutinib use, age, hypertension, and previous use of ACE inhibitors, angiotensin receptor blocker use, ß blocker use, and aspirin use were independently associated with incident arrhythmias. In multivariable analysis, patients treated with ibrutinib were associated with a 5-fold increased risk of developing AA (odds ratio = 5.18, 95% confidence interval 1.42 to 18.89). In conclusion, the rates and risk of AA are higher in patients treated with ibrutinib compared with chemotherapy, and this study provides strong evidence that ibrutinib itself is an independent risk factor for the development of incident AA.

Update on the management of Philadelphia chromosome positive chronic myelogenous leukemia: role of nilotinib.

Chronic myelogenous leukemia (CML) is a pluripotent stem cell disease characterized by the presence of the Philadelphia chromosome and the bcr-abl gene. The discovery of tyrosine kinase inhibitors (TKIs) revolutionized therapy for CML, such that durable response, increased overall survival, and increased progression-free survival of patients in chronic phase CML is now possible. Due to resistance and intolerance to imatinib, there was need for development of second- and third-generation TKIs for the treatment of CML. This review examines the role of nilotinib, an oral second-generation TKI, in the treatment of Philadelphia positive CML. The pharmacology, efficacy, and safety of nilotinib are critically evaluated. Patient-related issues, including tolerance, drug interactions, and quality of life issues are also examined.

Long-term BCR-ABL1 Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia.

With the success of tyrosine kinase inhibitor (TKI) therapy for the treatment of patients with chronic myeloid leukemia (CML), CML is now treated as a chronic disease. As such, the community of oncologists may see patients with CML more often than the primary-care physician and must focus on long-term management of adverse events and adherence. BCR-ABL1 TKIs are effective therapies in CML but are associated with distinct safety profiles. Thus, selection of long-term treatment with any TKI requires assessment of patient comorbidities and regular monitoring to identify the potential emergence of adverse effects or new risk factors. With a focus on long-term safety, this review provides a holistic picture of the primary care needs of patients with CML, emphasizing on the importance of community oncologists who in many cases act as both oncologists and primary-care physicians.

An update on current and prospective immunotherapies for chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common leukemia. Combined agent chemotherapy is the current standard front-line treatment for physically fit patients with CLL. Use of chemotherapy can be complicated by significant toxicity, especially in patients with advanced age or comorbid conditions. Moreover, patients may relapse and become refractory to further chemotherapy. Immunotherapy targets the aberrant immunological processes in CLL without the toxicity of chemotherapy. Immunotherapeutic strategies can also be combined with chemotherapy to improve response rates in this incurable disease. In this review, we evaluate current and future immune-based options in the treatment of CLL.