Blinatumomab Plus Chemotherapy Enhances Outcomes for Children with Newly Diagnosed B-Cell ALL
Over the past five decades, the cure rates for acute lymphoblastic leukemia (ALL) have greatly improved, although further progress has slowed. Blinatumomab has appeared hopeful in treating children with relapsed B-cell ALL by redirecting T cells to attack these cancer cells. However, its effect on children with newly diagnosed disease remained unclear.
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AALL1731, an international, randomized, controlled, phase 3 trial conducted by the Children's Oncology Group, assessed whether adding two cycles of blinatumomab to standard chemotherapy would produce better results for children with standard-risk B-cell ALL. The study ran from June 2019 to June 2024 and enrolled 1,440 children ages 1 to 10 with standard-risk B-cell ALL and with an average or high risk for relapse. The patients were randomized into two groups: one received chemotherapy alone, while the other received chemotherapy along with two cycles of blinatumomab. The primary endpoint was disease-free survival (DFS), defined as the time from randomization to the first event of relapse, death, or a second malignancy.
The results showed that adding blinatumomab improved DFS, with a 3-year DFS of 96% in the blinatumomab group versus 87.9% in the chemotherapy-only group. Additionally, blinatumomab was found to strengthen DFS across all subgroups, including those with varying minimal residual disease levels, race, and cytogenetic risk groups. Overall survival was also improved, particularly in patients with an average risk of relapse. Despite these positive results, patients in the blinatumomab group were more likely to experience severe infections, such as sepsis and catheter-related infections, although these events were relatively rare.
The findings from this trial suggest that blinatumomab could produce better treatment outcomes for children with newly diagnosed standard-risk B-cell ALL, particularly those with higher relapse risks. Although further studies are needed to address the optimal number of blinatumomab cycles and the long-term effects of the treatment, the results from this trial could help refine the strategies used to treat childhood leukemia in the future. (Gupta, S., et al. [2024]. Blinatumomab in standard-risk B-cell acute lymphoblastic leukemia in children. NEJM. Advance online publication. Retrieved December 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2411680?query=TOC&cid=DM2376567_Non_Subscriber&bid=-1601332578)
Released: January 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer
Brexpiprazole and Sertraline Combination a Promising Treatment for PTSD
Posttraumatic stress disorder (PTSD) is a mental health condition marked by intrusive memories, avoidance of trauma-related stimuli, and negative mood shifts. It impacts quality of life and is linked to increased suicide risk. First-line treatment for PTSD is selective serotonin reuptake inhibitors (SSRIs), such as sertraline and paroxetine, though many patients don't respond to these medications.
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One promising alternative is brexpiprazole, an antipsychotic with a broad range of pharmacologic effects on neurotransmitter systems. A phase 3, multicenter, double-blind, randomized clinical study compared brexpiprazole plus sertraline with sertraline plus placebo in patients diagnosed with PTSD to assess its efficacy, safety, and tolerability. The study ran from October 2019 to August 2023 and enrolled 416 patients. Participants were randomized to either brexpiprazole (2 to 3 mg/day) with sertraline (150 mg/day) or sertraline (150 mg/day) with placebo and monitored over 11 weeks.
The primary outcome of the study was the change in PTSD symptoms, as measured by the Clinician-Administered PTSD Scale (CAPS-5). Secondary outcomes included changes in global severity, psychosocial functioning, and anxiety and depression symptoms.
The results of the trial indicated that the addition of brexpiprazole to sertraline led to greater improvements in PTSD symptoms compared to sertraline and placebo. This was evident from the CAPS-5 scores, where the combination treatment showed a mean improvement of 19.2 points by week 10, compared to 13.6 points for the placebo group. The brexpiprazole group also showed improvements in anxiety and depression, psychosocial functioning, and PTSD symptom clusters.
The incidence of adverse events was similar between the two treatment arms, though the brexpiprazole group had slightly higher rates of weight gain, fatigue, and somnolence, primarily of mild to moderate severity. No serious adverse events were associated with the treatments.
This study supports the brexpiprazole and sertraline combination as an effective treatment for PTSD, particularly in patients who don't respond to SSRIs. Future research should explore the treatment's applicability to a broader range of PTSD patients and examine its long-term effects. (Davis, L. L., et al. [2024]. Brexpiprazole and sertraline combination treatment in posttraumatic stress disorder: A phase 3 randomized clinical trial. JAMA Psychiatry. Advance online publication. Retrieved December 2024 from https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2827796)
Released: January 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer
Imlunestrant Improves Progression-Free Survival for Patients with Breast Cancer
Estrogen receptor (ER)-positive, HER2-negative is the most common subtype of breast cancer and is typically treated with endocrine therapy. Despite improvements in outcomes through selective ER modulators and degraders, resistance can develop due to mutations in the ESR1 gene.
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Imlunestrant is an oral selective ER degrader, designed to target ESR1 mutations. The EMBER-3 trial tested imlunestrant both as monotherapy and in combination with abemaciclib in patients with ER-positive, HER2-negative advanced breast cancer. The phase 3, open-label trial ran from October 2021 through November 2023 and included 874 patients across 22 countries. Of the patients, 38.7% had ESR1 mutations, which were associated with a more challenging prognosis. Participants were randomized into three groups: imlunestrant alone, standard therapy (exemestane or fulvestrant), and imlunestrant plus abemaciclib. Progression-free survival (PFS) was the primary endpoint, with secondary endpoints including overall survival and adverse events.
At the primary analysis, the median PFS for patients with ESR1 mutations was 5.5 months in the imlunestrant group versus 3.8 months in the standard therapy group, showing a statistically significant benefit for imlunestrant. However, the combination of imlunestrant and abemaciclib resulted in the most improved PFS results with a median of 9.4 months, emphasizing the broader benefit of combining these therapies.
Adverse events with imlunestrant were similar to standard therapy, including fatigue, diarrhea, and nausea; but the imlunestrant–abemaciclib group produced a higher incidence of serious adverse events, particularly related to neutropenia and anemia.
This study showed that although imlunestrant is effective for patients with ESR1 mutations, the combination of imlunestrant and abemaciclib provided a more pronounced benefit across a broader range of patients, including those without ESR1 mutations. This combination offers an encouraging approach to overcoming resistance and improving patient outcomes in ER-positive, HER2-negative breast cancer. (Jhaveri, K. L., et al. [2024]. Imlunestrant with or without abemaciclib in advanced breast cancer. NEJM. Advance online publication. Retrieved December 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2410858)
Released: December 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer
Updated Dosing Guidance for MenB Vaccination
The Advisory Committee on Immunization Practices (ACIP) recommends vaccination against serogroup B meningococcal (MenB) disease for adolescents and young adults as well as those age 10 and older who are at higher risk for severe disease. ACIP guidelines now include two licensed MenB vaccines: MenB-FHbp (Trumenba) and MenB-4C (Bexsero). This report provides updated dosing guidance for MenB-4C while maintaining other previous vaccination recommendations.
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The ACIP's Meningococcal Vaccines Work Group reviewed clinical trial data from several studies, evaluating MenB-4C's effectiveness and safety. The data indicated varying rates of immune response after different dosing schedules, with higher response rates after a three-dose series. The safety profile showed that common adverse reactions, such as pain at the injection site, headache, and fatigue, were similar across different dosing schedules. In addition, MenB vaccines from different manufacturers are not interchangeable, so it's important that all doses in a series are from the same brand.
Based on this review, ACIP provides the following guidelines:
- MenB-4C should be delivered as two doses at 0 and 6 months for adolescents and young adults ages 16 to 23.
- For higher-risk individuals (age 10 and older with asplenia, complement deficiencies, complement inhibitor use, microbiologists exposed to Neisseria meningitidis, or those at heightened risk during an outbreak), a three-dose series at 0, 1 to 2, and 6 months is suggested.
- For individuals who start the MenB vaccine series within 6 months of a high-risk event (for example, college entry), the three-dose schedule is preferred to ensure rapid protection.
- Additional doses aren't recommended for those who have already received MenB-4C under previous dosing schedules, but booster doses should align with the original manufacturer.
(Schillie, S., et al. [2024]. New dosing interval and schedule for the Bexsero MenB-4C vaccine: Updated recommendations of the Advisory Committee on Immunization Practices–United States, October 2024. MMWR, 73[49], 1124–1128. Retrieved December 2024 from https://www.cdc.gov/mmwr/volumes/73/wr/mm7349a3.htm?s_cid=mm7349a3_w)
Released: January 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer