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Therapeutic Advances in Hematology
This article reviews the novel CXCR4 inhibitor motixafortide and its use in hematopoietic stem-cell mobilization. We present a history of stem-cell mobilization and update of recent innovations in novel mobilization strategies. Hematopoietic stem-cell mobilization is a crucial step in autologous stem-cell transplantation. Motixafortide is a novel CXCR4 inhibitor that has been shown in preclinical and clinical trials to mobilize hematopoietic stem cells (HSCs) for transplantation. The drug has extended in vivo activity (>48 h) and high affinity (Ki, 0.32 nM). In a phase 1, two-part study, motixafortide administered to healthy subjects was safe, well tolerated, and led to a rapid and robust increase in the number of circulating HSCs. Motixafortide has been evaluated in a randomized phase 3 trial for autologous transplantation in multiple myeloma. The study showed that the combination of motixafortide and granulocyte colony-stimulating factor (G-CSF) was superior to G-CSF alone in terms of the number of CD34+ cells collected and the time to engraftment. The drug has also been evaluated in combination with plerixafor, another CXCR4 inhibitor, in a phase 1/2 study for autologous transplantation in multiple myeloma. The study showed that the combination of motixafortide and plerixafor was safe and effective in mobilizing HSCs. Motixafortide has […]
Hematology May 30th 2023
OBR Oncology
ASCO 2023 abstracts: a glimpse into groundbreaking advancements in the oncology field. At the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Gilead Sciences and Kite Oncology are set to present 30 abstracts. Their data underscores their leadership in hard-to-treat cancers, notably metastatic breast cancer. In addition, they highlight a growing presence in lung cancer and other tumor types. Trodelvy® (sacituzumab govitecan-hziy) emerges as a promising treatment for HR+/HER2- metastatic breast cancer (mBC) with the final overall survival (OS) results from the Phase 3 TROPiCS-02 study. Its efficacy extends to metastatic urothelial cancer (UC) and advanced endometrial cancer, reinforcing its pan-tumor potential. Moreover, Yescarta® (axicabtagene ciloleucel) offers a ray of hope for adult patients with relapsed/refractory large B-cell lymphoma (LBCL). Notably, this CAR T-cell therapy demonstrates a statistical improvement over standard care in overall survival, marking a significant medical breakthrough. Gilead’s oncology pipeline, particularly for lung cancer, is expanding. The ongoing late-stage development program evaluates Trodelvy in non-small cell lung cancer (NSCLC). Also, the updated interim analysis of ARC-7, evaluating domvanalimab in first-line NSCLC, will be presented. Presentations at ASCO 2023 will also share trial updates from ongoing studies in lung cancer, triple-negative breast cancer, UC, and other solid […]
JAMA Network
Diving into intensive systolic BP treatment unveils intriguing cognitive benefits according to a secondary analysis of the SPRINT trial. The SPRINT trial has shed fresh light on the impact of intensive systolic blood pressure (SBP) treatment on cognitive health. Out of 7,918 participants, a significant majority with higher baseline risk of dementia or mild cognitive impairment (MCI) revealed marked cognitive improvements with intensive SBP treatment. This marks a leap forward in understanding SBP treatment’s role in cognitive function preservation. In the comprehensive secondary analysis, patients were meticulously followed up over a median of four years. To streamline the study, two SBP treatment targets were identified: intensive, set at less than 120 mm Hg, and standard, at less than 140 mm Hg. The data collected showcased 765 and 828 primary outcome events in intensive and standard treatment groups, respectively. Consequently, it confirmed intensive SBP treatment’s potential in reducing the risk of MCI or dementia. Digging deeper into the data, certain trends emerged. Older age, Medicare enrollment, and higher baseline serum creatinine levels correlated with a higher risk of the primary outcome. Conversely, enhanced baseline cognitive functioning and active employment status signified lower risk. Interestingly, higher baseline risk connected directly with greater […]
Cardiology May 23rd 2023
Epilepsy Currents
Dive into the intriguing findings from the PEACH trial on prophylactic levetiracetam for seizure prevention in intracerebral haemorrhage patients. The PEACH trial aimed to test prophylactic levetiracetam for seizure prevention in acute intracerebral haemorrhage (ICH) patients. Early seizures within seven days of stroke onset occur in almost 30% of patients. However, current guidelines lack strategies to manage this issue. Despite being prematurely stopped, the trial showed promise. In this double-blind, randomised, placebo-controlled trial, 50 patients received either levetiracetam or a placebo. Clinical or electrographic seizures were seen in 16% of levetiracetam patients and 43% of placebo patients within 72 hours. Interestingly, these seizures were only electrographic. Adverse events included headaches and pain, but no treatment-related deaths were reported. The findings suggest levetiracetam may prevent acute seizures in ICH patients, but larger studies are needed. Acute seizures can lead to increased morbidity and mortality. The trial found fewer seizures within 72 hours of study inclusion in the levetiracetam group. This is promising, but more research is required. This study opens avenues for further investigation. It raises questions about early detection of interictal epileptiform activity and the need for prophylactic levetiracetam. It also underscores the need to understand which factors influence seizure […]
Internal Medicine May 23rd 2023
The Journal of Clinical Investigation (JCI)
This study presents findings from a Phase I clinical trial examining the use of Stereotactic Body Radiotherapy (SBRT) combined with pembrolizumab (P) in treating advanced solid tumors, with a focus on the safety and effectiveness of partial tumor irradiation. The trial involved 97 patients, 47% of whom received at least one partial radiation treatment. The overall one-year local failure (LF) rate was 7.6%, and the results suggest an association between tumor response to SBRT+P and improved overall survival (OS), particularly for irradiated tumors. The trial also explored the role of biomarkers, finding that a high Radiomics Score (RS), based largely on CD8+ T cell levels, was linked to better LF, progression-free survival (PFS), and OS. Conversely, increased levels of circulating cytokine IL-8 were associated with worse PFS and OS. The study concluded that SBRT+P is safe for patients with large, advanced solid tumors and recommended further research to compare the effectiveness of complete versus partial tumor irradiation in the context of immunotherapy.
Oncology, Medical May 22nd 2023
The New England Journal of Medicine
In the phase III GAIA–CLL13 study, researchers investigated time-limited treatment options for fit patients with chronic lymphocytic leukemia (CLL) and a low burden of coexisting conditions. The study compared the efficacy of chemoimmunotherapy with venetoclax-obinutuzumab, both with and without ibrutinib. The results showed that the venetoclax-based regimens were superior to chemoimmunotherapy in terms of achieving undetectable minimal residual disease and longer progression-free survival (PFS). The percentages of patients with undetectable minimal residual disease were remarkably high, with 86.5% in the venetoclax-obinutuzumab group and 92.2% in the venetoclax-obinutuzumab-ibrutinib group, among the highest reported in first-line treatment for CLL. The study confirmed the significant prognostic value of undetectable minimal residual disease at the end of time-limited treatment, as it translated into superior PFS. The study emphasized the need for treatment options for fit CLL patients with normal renal function, as data from prospective, randomized clinical studies evaluating the safety and efficacy of venetoclax-obinutuzumab in this specific patient population were lacking. The study demonstrated that the venetoclax-obinutuzumab-ibrutinib combination had a higher incidence of tumor lysis syndrome compared to venetoclax-ibrutinib, likely due to the simultaneous administration of obinutuzumab with ibrutinib, leading to rapid depletion of CLL cells. The findings highlight the importance of continuing […]
Hematology May 22nd 2023