Comparing Safety and Efficacy of Chemotherapy Regimens for Hodgkin Lymphoma
Survival outcomes for advanced-stage classical Hodgkin lymphoma were poor before the advent of modern chemotherapy. The high-intensity regimen, eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), has been standard but is associated with serious toxicities. BrECADD, which incorporates the antibody-drug conjugate brentuximab vedotin, was developed to potentially offer comparable effectiveness with fewer toxic side effects. A study comparing the two chemotherapy regimens aimed to balance treatment efficacy with reduced toxicity, particularly focusing on long-term health impacts like organ dysfunction and infertility in young adults with Hodgkin lymphoma.
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The phase 3 randomized, multicenter, parallel, intergroup clinical trial was conducted between July 2016 and August 2020, and enrolled 1,500 patients (age 60 and younger) across multiple countries. Patients received cycles of either eBEACOPP or BrECADD (both initiated at full-dose level 4) administered in 21-day intervals. Positron emission tomography (PET) guided treatment adaptation to tailor therapy based on early response assessment.
Researchers sought to compare treatment-related morbidity and progression-free survival between the two regimens. BrECADD demonstrated significantly lower treatment-related morbidity rates, with 42% of patients experiencing at least one treatment-morbidity event compared to 59% of patients receiving eBEACOPP. Both groups achieved similar rates of complete remission post-chemotherapy, with a substantial proportion of patients benefiting from PET-guided treatment adjustments.
Regarding efficacy, BrECADD showed noninferiority and, in a subsequent analysis, superiority in progression-free survival compared to eBEACOPP (4-year progression-free survival for BrECADD was 94.3% versus 90.9% for eBEACOPP). Safety assessments included resolution of toxicities within a year posttreatment, showing generally manageable long-term impacts on patients' health. Additionally, BrECADD was associated with better preservation of gonadal function and fewer second primary malignancies compared to eBEACOPP.
Overall, the study supports BrECADD as a promising alternative to eBEACOPP for treating advanced-stage Hodgkin lymphoma, offering comparable efficacy with significantly reduced treatment-related toxicity. These findings are likely to influence future treatment guidelines and improve outcomes for young adults facing this challenging cancer diagnosis. (Borchmann, P., et al. (2024). Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): A randomised, multicentre, parallel, open-label, phase 3 trial. The Lancet. Advance online publication. Retrieved July 2024 from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01315-1/fulltext)
Released: August 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer
Cendakimab Improves Skin Symptoms in Severe Atopic Dermatitis
Atopic dermatitis, a chronic inflammatory skin condition, causes substantial patient burden including severe itching, sleep disturbances, and impacts on daily activities. When topical treatments are inadequate for moderate to severe atopic dermatitis, systemic therapies like biologics become necessary. Biologics approved for atopic dermatitis target interleukin (IL)-4 or IL-13 pathways due to their involvement in atopic dermatitis pathogenesis.
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Cendakimab, a monoclonal antibody targeting IL-13, was evaluated in a phase 2 randomized, double-blind, placebo-controlled clinical trial for its efficacy and safety in adults with moderate to severe atopic dermatitis. The study, which ran from May 2021 to November 2022, randomized 221 patients to receive varying doses of cendakimab (720 mg, once weekly; 720 mg, every 2 weeks; or 360 mg, every 2 weeks) or placebo for 16 weeks. Primary endpoints included improvement in Eczema Area and Severity Index (EASI) scores, with secondary endpoints focusing on skin clearance and pruritus reduction.
Overall, a larger proportion of cendakimab patients achieved a 75% or greater reduction in EASI (720 mg, once weekly: 50.0%; 720 mg, every 2 weeks: 48.2%; 360 mg, every 2 weeks: 52.7%) compared to placebo (26.3%). There was also a noticeable improvement in skin clearance in patients receiving 720-mg weekly cendakimab, with 33.3% of patients achieving a score of 0 (clear) or 1 (almost clear) than with placebo (9.4%). Safety assessments indicated manageable adverse events, with conjunctivitis being the most notable, consistent with other IL-13 inhibitors.
This study supports cendakimab as a potential therapeutic option for treating moderate to severe atopic dermatitis, particularly in reducing inflammation and improving skin symptoms. Further research could explore its long-term efficacy and broader applicability in diverse patient populations. (Blauvelt, A., et al. (2024). Cendakimab in patients with moderate to severe atopic dermatitis: A randomized clinical trial. JAMA Dermatology. Published online. Retrieved July 2024 from https://jamanetwork.com/journals/jamadermatology/fullarticle/2821285)
Released: August 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer
Efanesoctocog Alfa Manages Bleeding in Children with Severe Hemophilia A
Hemophilia A is characterized by deficiency in factor VIII, leading to recurrent bleeding episodes, particularly into joints, despite current therapies. Standard treatments require frequent injections due to their limited duration of action, which poses challenges for adherence, especially in children. XTEND-Kids, a phase 3 open-label, international, single-group study, evaluated efanesoctocog alfa, a new factor VIII replacement therapy, in previously treated children with severe hemophilia A. Efanesoctocog alfa is designed to extend factor VIII half-life, which allows for weekly dosing, potentially improving treatment adherence.
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The study enrolled 74 patients (younger than age 12) who received prophylactic intravenous efanesoctocog alfa (50 IU/kg) once per week for 52 weeks. For bleeding episodes, one dose of efanesoctocog alfa (50 IU/kg) was given, with additional 30 or 50 IU/kg doses every 2 or 3 days, as needed. The primary endpoint was the development of inhibitors to factor VIII, which did not occur in any patient. Adverse events were mostly nonserious, and no treatment discontinuations due to adverse effects were reported.
Efanesoctocog provided effective bleeding prevention, with a median annualized bleeding rate of 0.00 and a mean rate of 0.89. Bleeding episodes were likewise managed efficiently, with most resolved using a single injection. Joint health showed overall improvement, indicating potential long-term benefits in joint preservation. In addition, sustained factor VIII levels above therapeutic thresholds were observed for up to 7 days, supporting the weekly prophylactic dosing.
Demonstrating promising safety and efficacy profiles in children with severe hemophilia A, efanesoctocog alpha offers a convenient weekly prophylactic option that may enhance treatment outcomes and patient quality of life compared to current therapies. Future studies will further explore its long-term safety and efficacy, including for previously untreated patients and different age groups. (Malec, L., et al. (2024). Efanesoctocog alfa prophylaxis for children with severe hemophilia A. N Engl J Med, 391, 235—246. Retrieved July 2024 from https://www.nejm.org/doi/abs/10.1056/NEJMoa2312611)
Released: August 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer
Lowering LDL Cholesterol with Lerodalcibep in Patients with or at Risk for Cardiovascular Disease
Recent updates to lipid guidelines suggest more aggressive treatment for lowering LDL cholesterol to prevent cardiovascular (CV) events, advocating for additional medications and stricter targets if statins alone are insufficient. However, lerodalcibep, a third-generation PCSK9 inhibitor, appears effective in achieving these lower targets.
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Lerodalcibep works by blocking proprotein convertase subtilisin/kexin type 9 (PCSK9) from binding to LDL cholesterol, thereby enhancing cholesterol clearance without significant safety concerns. The drug combines adnectin, an anti-PCSK9 binding protein, with human serum albumin, allowing for a smaller injection volume compared to existing monoclonal antibodies.
The phase 3 LIBerate-HR study aimed to evaluate the effectiveness of lerodalcibep in lowering LDL cholesterol in patients at risk for CV disease. The study included 922 patients, with or at high risk for CV disease, randomized to receive monthly subcutaneous injections of lerodalcibep (300 mg) or placebo for 52 weeks. Results showed that lerodalcibep achieved a profound reduction in LDL cholesterol, with 94% of treated patients achieving at least a 50% reduction compared to placebo (19%). The drug also lowered non-HDL cholesterol (−47.3%), apolipoprotein B (−43%), lipoprotein(a) (−33.4%), and triglycerides (−16.5%) while increasing HDL cholesterol by 6.5%. Safety profiles were similar to placebo, with manageable injection-site reactions and no immunogenicity issues reported.
Lerodalcibep may be a versatile option for patients needing PCSK9 inhibitors, with the advantage of monthly injections over bi-weekly injections required by current monoclonal antibodies. However, concerns remain regarding long-term safety and immunogenicity, given past issues with other PCSK9 inhibitors like bococizumab.
Results of this study show lerodalcibep to be an effective and well-tolerated PCSK9 inhibitor, potentially enhancing treatment options for patients with or at high risk for CV disease, pending further regulatory and safety evaluations. (Maxwell, Y. L. (2024). LIBerate-HR: Lerodalcibep lowers LDL more sharply than placebo over 1 year. TCTMD. Retrieved July 2024 from https://www.tctmd.com/news/now-published-liberate-hr-lerodalcibep-lowers-ldl-more-sharply-placebo-over-1-year; Klug, E. Q., et al. (2024). Efficacy and safety of lerodalcibep in patients with or at high risk of cardiovascular disease: A randomized clinical trial. JAMA Cardiol. Advance online publication. Retrieved July 2024 from https://jamanetwork.com/journals/jamacardiology/article-abstract/2820248)
Released: August 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer