- |||||||||| Journal: Integrating Vascular Phenotypic and Proteomic Analysis in an Open Microfluidic Platform. (Pubmed Central) - Sep 1, 2024
We study the effects of antiangiogenic agents?bevacizumab, ramucirumab, cabozantinib, regorafenib, wortmannin, chloroquine, and paclitaxel?on cytoskeletal integrity and angiogenic sprouting, observing an approximately 50% reduction in sprouting at higher drug concentrations...Our findings emphasize the intricate relationship between cytoskeletal alterations and angiogenic responses, underlining the significance of integrating morphological and proteomic data for a comprehensive understanding of angiogenesis. The VPT platform not only advances our understanding of drug impacts on vascular biology but also offers a versatile tool for analyzing proteome and morphological features across various models beyond blood vessels.
- |||||||||| Neulasta (pegfilgrastim) / Roche
Journal: Dispensed prescription medications and short-term risk of pulmonary embolism in Norway and Sweden. (Pubmed Central) - Sep 1, 2024
Mineral supplements, hydrochlorothiazide and potassium-sparing agents, beta-blockers, angiotensin 2 receptor blockers, statins, and methotrexate were associated with lower risk...These results provide exploratory, pharmacopeia-wide evidence of medications that may increase or decrease the risk of pulmonary embolism. Some of these findings were expected based on the drugs' indications, while others are novel and require further study as potentially modifiable precipitants of pulmonary embolism.
- |||||||||| Vectibix (panitumumab) / Amgen
Clinical, Review, Journal: Hazard Ratios and Alternative Effect Measures: An (Pubmed Central) - Sep 1, 2024
We report that clinically achievable doses of navtemadlin induce pharmacodynamic effects in tumor tissue, and suggest combinations with standard-of-care chemotherapy for durable clinical benefit. This example underscores the difficulties in interpreting HRs, particularly in the setting of qualitative violations of proportional hazards, and the value of quantifying treatment effects via multiple effect measures.
- |||||||||| Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen, DCC-3116 / Ono Pharma
Preclinical, Journal: Inhibition of ULK1/2 and KRASG12C controls tumor growth in preclinical models of lung cancer. (Pubmed Central) - Sep 1, 2024
Additionally, in genetically engineered mouse models of KRASG12C-driven NSCLC, inhibition of either KRASG12C or ULK1/2 decreases tumor burden and increases mouse survival. Consequently, these data suggest that ULK1/2-mediated autophagy is a pharmacologically actionable cytoprotective stress response to inhibition of KRASG12C in lung cancer.
- |||||||||| Ibrance (palbociclib) / Pfizer, Kisqali (ribociclib) / Novartis, Verzenio (abemaciclib) / Eli Lilly
Journal, Adverse events, Real-world evidence, Real-world: Profiling the Cardiovascular Toxicities of CDK4/6 Inhibitors: A Real-World Pharmacovigilance Study. (Pubmed Central) - Aug 31, 2024
This study demonstrates that the use of CDK4/6 inhibitors is associated with cardiovascular adverse events, such as heart failure and hypertension. Further research is needed to understand the mechanisms and risk factors contributing to the cardiovascular toxicity of CDK4/6 inhibitors.
- |||||||||| Ibrance (palbociclib) / Pfizer
Journal: EWS-WT1 fusion isoforms establish oncogenic programs and therapeutic vulnerabilities in desmoplastic small round cell tumors. (Pubmed Central) - Aug 31, 2024
Finally, we identify candidate EWS-WT1 target genes with potential therapeutic implications, including CCND1, whose inhibition by the clinically-approved drug Palbociclib leads to marked tumor burden decrease in DSRCT PDXs in vivo. Taken together, our studies identify gene regulation programs and therapeutic vulnerabilities in DSRCT and provide a mechanistic understanding of the complex oncogenic activity of EWS-WT1.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, Vectibix (panitumumab) / Amgen
Journal, HEOR, Real-world evidence, Cost-effectiveness, Cost effectiveness, Real-world, Metastases: Real-world cost-effectiveness of panel-based genomic testing to inform therapeutic decisions for metastatic colorectal cancer. (Pubmed Central) - Aug 31, 2024
The use of OncoPanel resulted in more precise targeting of cetuximab and panitumumab, but there was no change in incremental cost or quality-adjusted survival. Understanding the balance of costs achieved in practice can provide insight into the effect of future changes in testing policy, test cost, treatment eligibility, or drug prices in this setting.
- |||||||||| Prolia (denosumab) / Amgen, Evenity (romosozumab-aqqg) / Astellas, Amgen, UCB
Journal: A novel sequential treatment approach between denosumab and romosozumab in patients with severe osteoporosis. (Pubmed Central) - Aug 31, 2024
A novel overlapping sequential treatment approach between denosumab and romosozumab produced greater improvements in lumbar spine and hip BMD than previously reported with standard approaches. Larger prospective controlled studies are needed to confirm these findings and establish the optimal use of romosozumab in patients pre-treated with denosumab to maximise BMD gains and minimise fracture risk.
- |||||||||| Progress in Lower-Risk MDS () - Aug 30, 2024 - Abstract #SOHO2024SOHO_1041;
Roxadustat, an oral HIF1- alpha hydroxylase inhibitor, was approved for treating anemia in Europe and China for chronic renal insufficiency...Both romiplostim and eltrombopag are approved for treating immune thrombocytopenic purpura, but their use in LR- MDS is still off label...Conclusions Significant progress has been obtained in treating anemia in LR- MDS, but there is still room for improvement by building a strategy to optimize the sequence of therapies with agents with different mechanisms of action and by evaluating combinations of them to achieve long-lasting TI. Target therapies like ivosidenib, a mutant IDH1 inhibitor, could be a candidate for LR-MDS cases with this mutation, as suggested by pivotal studies.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Enhancing Precision Treatment for Childhood Acute Lymphoblastic Leukemia () - Aug 30, 2024 - Abstract #SOHO2024SOHO_1040;
This strategy allows the agents to act synergistically to kill leukemia cells while sparing normal tissues from excessive toxicity. Acknowledgement Supported in part by US National Cancer Institute Grant CA021765 and by American Lebanese Syrian Associated Charities (ALSAC).
- |||||||||| Scemblix (asciminib) / Novartis, Iclusig (ponatinib) / Takeda, Otsuka, Blincyto (blinatumomab) / Astellas, Amgen
Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia can be Treated with Chemotherapy-Free Regimens without Transplant () - Aug 30, 2024 - Abstract #SOHO2024SOHO_1039;
Acknowledgement Supported in part by US National Cancer Institute Grant CA021765 and by American Lebanese Syrian Associated Charities (ALSAC). Significant progress has been made in recent years in the treatment of adults with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL).1 Combining BCR::ABL1 tyrosine kinase inhibitors (TKIs) with intensive chemotherapy regimens like hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) and others has greatly improved patient outcomes.2 As a result, allogeneic hematopoietic stem cell transplantation (HSCT) has become an additional valuable option...Specifically, the 5-year PFS rates were 81% with hyper-CVAD plus ponatinib, 54% with hyper-CVAD plus dasatinib, and 64% with hyper-CVAD plus imatinib...In contrast to the D-ALBA trial, only two patients underwent HSCT.26 Whether the combination of blinatumomab and ponatinib can overcome the poor prognosis of IKZF1plus and the negative impact of an elevated white blood cell count (higher than 70
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Transplant in Adult ALL: Who and When () - Aug 30, 2024 - Abstract #SOHO2024SOHO_1038;
Similarly, a multicenter analysis of 83 patients with Ph-like ALL undergoing transplant in CR1 demonstrated that patients with Ph-like ALL had higher rates of induction failure but responded to blinatumomab becoming MRD negative prior to transplant. Notably, after transplant, outcomes for Ph-like patients were comparable to other Ph-negative subtypes.4 Studies investigating the differential risk of Ph-like subsets are ongoing, but the sum observations of currently published studies suggest benefit for transplant in CR1.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Development of Inotuzumab Ozogamicin and Blinatumomab for Frontline Treatment of Older Patients with Ph-Negative B-Cell Acute Lymphoblastic Leukemia () - Aug 30, 2024 - Abstract #SOHO2024SOHO_1025;
In the single-arm, phase II INITIAL-1 trial (median age 64 years), the GMALL group administered 3 cycles of InO with dexamethasone as remission induction therapy, followed by reduced-intensity chemotherapy, and then maintenance therapy with mercaptopurine and methotrexate...With 15 months of follow-up, the estimated 1-year OS and leukemia-free survival rates were 73% and 65%, respectively.7 Similarly, MD Anderson studied a reduced-dose InO in combination with mini-hyperCVD (dose-reduced cyclophosphamide, vincristine, and dexamethasone, alternating with methotrexate and cytarabine) regimen in older patients (median age 68 years)...Elimination of conventional chemotherapy by using highly active targeted agents is highly effective in Ph-positive ALL, and the preliminary results for InO and blinatumomab with either dose-reduced or no conventional chemotherapy support some of these approaches as valid options for the treatment of older patients in clinical practice. Given this success, the integration of additional targeted agents holds promise to further improve outcomes for older and, by extension, younger patients with B-cell ALL, thereby representing a new paradigm of older-adult-inspired therapy for ALL.
- |||||||||| Nplate (romiplostim) / Amgen, Kyowa Kirin
Place of Romiplostim in the Treatment of Bone Marrow Aplasia (LEVEL 3, HALL B3) - Aug 30, 2024 - Abstract #SOHO2024SOHO_954;
Romiplostim constitutes a therapeutic alternative in patients suffering from AA, whether or not they are eligible for bone marrow transplantation. In our series, it was possible to maintain an average platelet level around 45,000/ mm3, thus lowering the risk of hemorrhage.
- |||||||||| Tecvayli (teclistamab-cqyv) / Genmab, J&J
Teclistamab Success in CAR-T Refractory Multiple Myeloma: A Case Presentation (LEVEL 3, HALL B3) - Aug 30, 2024 - Abstract #SOHO2024SOHO_862;
She developed cytokine-release-syndrome (CRS), for which she received tocilizumab and 3 days of dexamethasone in ICU...She received subcutaneous denosumab 120 mg for bone disease... Prospective trials are needed to determine the optimal timing and use of teclistamab and other T-cell-redirecting therapies to increase the likelihood of cure for patients with myeloma.
- |||||||||| tapotoclax (AMG 176) / Amgen
A Phase I Study of the Myeloid (LEVEL 3, HALL B3) - Aug 30, 2024 - Abstract #SOHO2024SOHO_595;
P1
No DLTs were observed, and cardiac AEs self-resolved without dose reductions. Given its manageable toxicity profile and transient antileukemic and transfusion-independent effect, the use of tapotoclax in combination with HMA or other therapies may warrant further consideration.
- |||||||||| Myeloid Sarcoma and Lymphoid Sarcoma of the Brain: A Case Series (LEVEL 3, HALL B3) - Aug 30, 2024 - Abstract #SOHO2024SOHO_473;
Achieved imaging response of MS with fludarabine, idarubicin, cytarabine, and ponatinib...Treated with fludarabine, cytarabine, and venetoclax...BMB relapse after SCT was managed with miniCVD + inotuzumab + blinatumomab and she developed spinal leptomeningeal involvement at three years from presentation... CNS MS and LS are challenging, and treatment must be individualized.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Adult Onset Familial Common B-Cell Acute Lymphoblastic Leukemia With Shared ZEB2 Mutation (LEVEL 3, HALL B3) - Aug 30, 2024 - Abstract #SOHO2024SOHO_327;
The pathogenic role of this abnormality is not clear, as it was associated with other, possibly pathogenic mutations, but it might have played a role in leukemogenesis. The patients were treated successfully with novel therapeutic regimens.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Comparable Outcomes of Relapsed Acute Lymphoblastic Leukemia in Adolescents and Young Adults (AYA) Treated With Pediatric-Inspired Chemotherapy (R3 Protocol) Versus Adult-Based Salvage (FA) Protocol (LEVEL 3, HALL B3) - Aug 30, 2024 - Abstract #SOHO2024SOHO_322;
Salvage treatment with blinatumomab for adults with relapsed B-cell ALL results in a complete remission (CR) rate of 34%, a median survival of 7.7 months, and an overall survival (OS) of less than 30% at 18 months...Therefore, this study aims to compare the outcomes of AYA patients treated with a pediatric-inspired regimen (R3 protocol) to those treated with an adult-based regimen (FA [fludarabine/ cytarabine] protocol)... Pediatric-inspired protocols that have shown significant benefits in the front-line setting for ALL in the AYA population did not demonstrate a significant difference when compared to traditional adult-based salvage chemotherapy regimens in relapsed disease.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Blinatumomab in the Treatment of Relapsed Refractory B-ALL: Case Report (LEVEL 3, HALL B3) - Aug 30, 2024 - Abstract #SOHO2024SOHO_318;
Pediatric-inspired protocols that have shown significant benefits in the front-line setting for ALL in the AYA population did not demonstrate a significant difference when compared to traditional adult-based salvage chemotherapy regimens in relapsed disease. Our case illustrated that the single-agent blinatumomab is a safe and effective treatment in patients with refractory bone marrow relapse with blasts greater than 40% as a bridge therapy before Allo-HSCT.
- |||||||||| Prolia (denosumab) / Amgen
Journal, Surgery: Piezoelectric Surgery, Er:YAG Laser Surgery and Nd:YAG Laser Photobiomodulation: A Combined Approach to Treat Medication-Related Osteonecrosis of the Jaws (MRONJ). (Pubmed Central) - Aug 28, 2024
This study aimed to propose a combined surgical approach with a piezoelectric device and laser (Er:YAG for bone ablation and Nd:YAG laser for photobiomodulation) in a young patient with breast cancer and bone metastasis under denosumab treatment, affected by spontaneous stage 3 MRONJ with maxillary sinus involvement...Total mucosal healing was observed without recurrences for more than 4 years after surgery. According to the results of our preliminary study, a combined surgical approach using a piezoelectric device and laser therapy is effective in managing patients affected by MRONJ, leveraging the clinical and biological advantages of these different techniques.
- |||||||||| Tepezza (teprotumumab-trbw) / Roche, Amgen
Review, Journal: Patterns of Teprotumumab-Induced Hearing Dysfunction: A Systematic Review. (Pubmed Central) - Aug 28, 2024
Hearing loss occurs primarily in higher frequencies, and routine hearing screening with ultrahigh frequency testing may be warranted. The true incidence of ototoxicity with teprotumumab remains unknown, and more data is needed to elucidate underlying mechanisms and develop strategies to minimize risks.
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