Ukoniq (umbralisib): Drug Safety Communication - FDA Approval of Lymphoma Medicine is Withdrawn Due to Safety Concerns
BACKGROUND Ukoniq was approved to treat two specific types of lymphoma: marginal zone lymphoma and follicular lymphoma.
Health care professionals should stop prescribing Ukoniq and switch patients to alternative treatments. Inform patients currently taking Ukoniq of the increased risk of death seen in the clinical trial and advise them to stop taking the medicine. In limited circumstances in which a patient may be receiving benefit from Ukoniq, TG Therapeutics plans to make it available under expanded access.
Patients should talk to your health care professionals about alternative treatments and stop taking Ukoniq. It is best to dispose of unused Ukoniq using a drug take-back location such as in a pharmacy, but if one is not available, you can dispose of Ukoniq in your household trash by doing the following:
Health care professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:
Source: FDA Published: June 1, 2021
A Multicentre, Open-Label Phase 2 Trial
AUDIENCE: Family Medicine, Oncology
KEY FINDINGS: Patients aged at least 65 years, with advanced oesophageal squamous cell carcinoma might benefit from combined nivolumab and ipilimumab therapy in second-line treatment.
BACKGROUND: The overall survival of patients with advanced and refractory oesophageal squamous cell carcinoma, mostly aged 65 years and older, is poor. Treatment with PD-1 antibodies showed improved progression-free survival and overall survival. Assessed the safety and efficacy of combined nivolumab and ipilimumab therapy in this population.
DETAILS: This multicentre, open-label, phase 2 trial done in 32 sites in Germany included patients aged 65 years and older with oesophageal squamous cell carcinoma and disease progression or recurrence following first-line therapy. Patients were treated with nivolumab (240 mg fixed dose once every 2 weeks, intravenously) in the safety run-in phase and continued with nivolumab and ipilimumab (nivolumab 240 mg fixed dose once every 2 weeks and ipilimumab 1 mg/kg once every 6 weeks, intravenously). The primary endpoint was overall survival, which was compared with a historical cohort receiving standard chemotherapy in the intention-to-treat population. Between March 2, 2018, and Aug 20, 2020, we screened 75 patients with advanced oesophageal squamous cell carcinoma. We enrolled 66 patients (50 [76%] men and 16 [24%] women; median age 70.5 years [IQR 67.0-76.0]), 44 (67%) of whom received combined nivolumab and ipilimumab therapy and 22 (33%) received nivolumab alone. Median overall survival time at the prespecified data cutoff was 7.2 months (95% CI 5.7-12.4) and significantly higher than in a historical cohort receiving standard chemotherapy (p=0.0063). The most common treatment-related adverse events were fatigue (12 [29%] of 42), nausea (11 [26%]), and diarrhoea (ten [24%]). Grade 3-5 treatment-related adverse events occurred in 13 (20%) of 66 patients. Treatment-related death occurred in one patient with bronchiolitis obliterans while on nivolumab and ipilimumab treatment.
Copyright © Elsevier Ltd. All rights reserved.
Source: Ebert, M. P., Meindl-Beinker, N. M., Gutting, T., et al. (2022). Second-line Therapy With Nivolumab Plus Ipilimumab For Older Patients With Oesophageal Squamous Cell Cancer (RAMONA): A Multicentre, Open-Label Phase 2 Trial. The Lancet. 2022; 3(6): 417-427. Published: June 1, 2022. DOI: 10.1016/S2666-7568(22)00116-7.
AUDIENCE: Ob/Gyn, Oncology, Family Medicine
KEY FINDINGS: In EC patients with coexistent adenomyosis, the risk of death is halved compared with EC patients without adenomyosis. However, the independence of this association needs to be verified in future studies.
BACKGROUND: Despite the high prevalence of adenomyosis in hysterectomy specimens of endometrial carcinoma (EC) patients, the relationship between adenomyosis and EC prognosis appears unclear. Aim of the study was to assess the prognostic value of coexistent adenomyosis in patients with EC.
DETAILS: A systematic review and meta-analysis was performed by searching six electronic databases for studies reporting data on prognosis of EC patients with and without coexistent adenomyosis. Studies with patient selection based on prognostic factors were excluded. Pooled univariate hazard ratio (HR) analyses for overall survival (OS) and disease-free survival (DRF) were performed, using EC patients without adenomyosis as a control group. For DFS, pooled multivariate HR analysis was also evaluable. Three studies of 2505 EC patients (553 with and 1952 without adenomyosis) were included. Compared with EC patients without adenomyosis, EC patients with coexistent adenomyosis showed a pooled HR of 0.533 (CI 95%, 0.329-0.864) for OS at univariate analysis; 0.536 (CI 95%, 0.334-0.859) for DFS at univariate analysis; and 0.875 (CI 95%, 0.331-2.315) for DFS at multivariate analysis.
Copyright © John Wiley & Sons, Inc. All rights reserved
Source: Raimondo, D., Raffone, A., Travaglino, A., et al. (2022). Impact of Adenomyosis On The Prognosis Of Patients With Endometrial Cancer. Intl J Gynecol Obstet.. 2022; 157(2): 265-270. Published: May, 2022. DOI: 10.1002/ijgo.13818.
AUDIENCE: Hematology, Family Medicine
KEY FINDINGS: Interferon alfa-2b is approved in treatment-naive patients and for patients with hydroxyurea resistance or intolerance, and ruxolitinib, a Janus kinase 1/2 inhibitor is exclusively approved for second-line treatment.
BACKGROUND: The clinical triumvirate of polycythemia vera include disease-related symptoms, vascular events, and transformation to myelofibrosis or blast phase.
DETAILS: Regulatory approval for polycythemia vera directed therapy is dependent on the achievement of a complete hematological response or phlebotomy associated goals (short-term clinical trial endpoints) that might not affect the most clinically relevant outcome measures of thrombosis, progression, and overall survival due to longer time to event, and lower incidence, which make polycythemia vera a challenging disease to evaluate in prospective trials. Although hydroxyurea is the mainstay of treatment in patients with polycythemia vera, approximately 15% of patients develop resistance or intolerance, which is deemed an adverse prognostic factor with higher risk for death (hazard ratio [HR] 5.6, 95% CI 2.7-11.9; p<0.001) and transformation to myelofibrosis or blast phase (HR 6.8, 3.0-15.4; p<0.001).
Copyright © Elsevier Ltd. All rights reserved.
Source: Venugopal, S. and Mascarenhas, J. (2022). Ruxolitinib In Patients With Polycythemia Vera With Hydroxyurea Resistance Or Intolerance. The Lancet. Published: May 18, 2022. DOI: 10.1016/S2352-3026(22)00139-9.
AUDIENCE: General Surgery, Oncology
KEY FINDINGS: Jet injectors generate a high number of small-droplet aerosols, potentially introducing harmful effects to patients and healthcare personnel. Room ventilation and smoke evacuation are effective safety measures when chemotherapeutics are used in clinical practice.
BACKGROUND: Needle-free jet injectors are frequently used in dermatological practice. Injection-generated small-droplet aerosols could be harmful upon inhalation when chemotherapeutics, like bleomycin, are used. Here, we aim to explore jet injector-induced small-droplet aerosol formation of bleomycin in relation to air ventilation and to provide safety measures for clinical practice.
DETAILS: With a professional particle sensor, during the study measured airborne aerosol particles (0.2-10. µm) after electronic pneumatic injection (EPI), spring-loaded jet injection (SLI), and needle injection (NI) of bleomycin and saline (100 µl) on ex vivo human skin. Three levels of air ventilation were explored: no ventilation, room ventilation, and room ventilation with an additional smoke evacuator. EPI and SLI induced significant small-droplet aerosol formation compared with none after NI (0.2-1.0 µm; no ventilation). The largest bleomycin aerosol generation was observed for the smallest particles (0.2-1.0 µm) with 673.170 (528.802-789.453) aerosol particles/liter air (EPI; no ventilation). Room ventilation and smoke evacuation led to a reduction of >=99% and 100% of measured aerosols, respectively.
Copyright © Wiley Periodicals LLC. All rights reserved
Source: Bik, L., Wolkerstorfer, A., Bekkers, V., et al. (2022). Needle-free Jet Injection-Induced Small-Droplet Aerosol Formation During Intralesional Bleomycin Therapy. Lasers Surg. Med.. 2022; 54(4): 572-579. Published: April, 2022. DOI: 10.1002/lsm.23512.
AUDIENCE: Oncology, Pediatric, Internal Medicine
KEY FINDINGS: In addition to leukemia, RAI treatment for childhood and young-adulthood DTC was associated with increased risks of several solid cancers, particularly more than 20 years after exposure, supporting the need for long-term surveillance of these patients.
BACKGROUND: Since the 1980s, both the incidence of differentiated thyroid cancer (DTC) and use of radioactive iodine (RAI) treatment increased markedly. RAI has been associated with an increased risk of leukemia, but risks of second solid malignancies remain unclear. We aimed to quantify risks of second malignancies associated with RAI treatment for DTC in children and young adults, who are more susceptible than older adults to the late effects of radiation.
DETAILS: Using nine US SEER cancer registries (1975-2017), estimated relative risks (RRs) for solid and hematologic malignancies associated with RAI (yes v no or unknown) using Poisson regression among >= 5- and >= 2-year survivors of nonmetastatic DTC diagnosed before age 45 years, respectively. Among 27,050 >= 5-year survivors (median follow-up = 15 years), RAI treatment (45%) was associated with increased risk of solid malignancies (RR = 1.23; 95% CI, 1.11 to 1.37). Risks were increased for uterine cancer (RR = 1.55; 95% CI, 1.03 to 2.32) and nonsignificantly for cancers of the salivary gland (RR = 2.15; 95% CI, 0.91 to 5.08), stomach (RR = 1.61; 95% CI, 0.70 to 3.69), lung (RR = 1.42; 95% CI, 0.97 to 2.08), and female breast (RR = 1.18; 95% CI, 0.99 to 1.40). Risks of total solid and female breast cancer, the most common cancer type, were highest among >= 20-year DTC survivors (RRsolid = 1.47; 95% CI, 1.24 to 1.74; RRbreast = 1.46; 95% CI, 1.10 to 1.95). Among 32,171 >= 2-year survivors, RAI was associated with increased risk of hematologic malignancies (RR = 1.51; 95% CI, 1.08 to 2.01), including leukemia (RR = 1.92; 95% CI, 1.04 to 3.56). We estimated that 6% of solid and 14% of hematologic malignancies in pediatric and young adult DTC survivors may be attributable to RAI.
Copyright © American Society of Clinical Oncology
Source: Pasqual, E., Schonfeld, S., Morton, L. M., et al. (2022). Association Between Radioactive Iodine Treatment for Pediatric and Young Adulthood Differentiated Thyroid Cancer and Risk of Second Primary Malignancies. ournal of Clinical Oncology . 2022; 40(13): 1439-1449. Published: May 1, 2022. DOI: 10.1200/JCO.21.01841.