Aflibercept is a recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF), a key regulator of angiogenesis. It binds to all isoforms of VEGF-A as well as VEGF-B and placental growth factor, and, thus, prevents them from binding to and activating their cognate receptors. In the USA and EU, intravenously administered aflibercept in combination with an infusion of leucovorin, fluorouracil and irinotecan (FOLFIRI) is approved for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after treatment with an oxaliplatin-containing regimen. The efficacy of aflibercept in this indication was assessed in a multinational, pivotal phase 3 trial (VELOUR), in which the approved regimen of aflibercept 4 mg/kg every 2 weeks plus FOLFIRI significantly prolonged median overall survival by 1.44 months compared with FOLFIRI alone (primary endpoint). The addition of aflibercept also significantly prolonged progression-free survival and significantly increased the objective response rate compared with FOLFIRI alone. Addition of aflibercept to FOLFIRI was associated with anti-VEGF-related adverse events and an increased incidence of FOLFIRI-related adverse events, but the tolerability of the combination was generally acceptable in this pre-treated population. The most common grade 3 or 4 adverse events with aflibercept plus FOLFIRI included neutropenia, diarrhoea and hypertension. In conclusion, aflibercept plus FOLFIRI is a useful treatment option for patients with metastatic colorectal cancer previously treated with an oxaliplatin-containing regimen, with or without bevacizumab.

Aflibercept: A Review in Metastatic Colorectal Cancer

/pdf/impact-of-daratumumab-based-induction-on-stem-cell-3qsszr4a.pdf

Impact of daratumumab-based induction on stem cell collection parameters in Swedish myeloma patients

Glioblastoma is the most aggressive and malignant primary brain tumor in adults and has a poor patient survival of only 20 months after diagnosis. This poor patient survival is at least partly caused by glioblastoma stem cells (GSCs), which are slowly-dividing and therefore therapy-resistant. GSCs are localized in protective hypoxic peri-arteriolar niches where these aforementioned stemness properties are maintained. We previously showed that hypoxic peri-arteriolar GSC niches in human glioblastoma are functionally similar to hypoxic peri-arteriolar hematopoietic stem cell (HSC) niches in human bone marrow. GSCs and HSCs express the receptor C-X-C receptor type 4 (CXCR4), which binds to the chemoattractant stromal-derived factor-1α (SDF-1α), which is highly expressed in GSC niches in glioblastoma and HSC niches in bone marrow. This receptor–ligand interaction retains the GSCs/HSCs in their niches and thereby maintains their slowly-dividing state. In acute myeloid leukemia (AML), leukemic cells use the SDF-1α–CXCR4 interaction to migrate to HSC niches and become slowly-dividing and therapy-resistant leukemic stem cells (LSCs). In this communication, we aim to elucidate how disruption of the SDF-1α–CXCR4 interaction using the FDA-approved CXCR4 inhibitor plerixafor (AMD3100) may be used to force slowly-dividing cancer stem cells out of their niches in glioblastoma and AML. Ultimately, this strategy aims to induce GSC and LSC differentiation and their sensitization to therapy.

CXCR4 Antagonists as Stem Cell Mobilizers and Therapy Sensitizers for Acute Myeloid Leukemia and Glioblastoma

Stem Cell Mobilization for Multiple Myeloma Patients Receiving Daratumumab-Based Induction Therapy: A Real- World Experience

Since the introduction of lenalidomide into induction therapy for multiple myeloma (MM), there have been conflicting reports about its impact on autologous peripheral blood stem cell (PBSC) mobilization. We evaluated the impact of previous lenalidomide exposure in a large cohort of patients with MM undergoing mobilization and collection at a tertiary stem cell transplantation center. We hypothesized that collection of PBSCs is feasible even with a prolonged duration of previous lenalidomide therapy. We examined patients with MM who attempted stem cell mobilization and collection, seen at our center between January 2012 and July 2015. The patients were categorized into 3 groups for analysis: (1) patients with previous receipt of >6 cycles lenalidomide, (2) patients with previous receipt of ≤6 cycles of lenalidomide, and (3) patients without previous lenalidomide exposure. We compared collection yields and days of apheresis among the 3 groups using linear regression analysis. We identified 297 patients with MM who underwent mobilization of PBSCs. Of these, 35 had received >6 cycles of lenalidomide (median, 8 cycles; range, 7 to 25 cycles), 156 had received ≤6 cycles of lenalidomide (median, 4 cycles; range, 1 to 6 cycles), and 106 had received no lenalidomide. Prior lenalidomide exposure did not have a statistically significant impact on the absolute number of CD34+ cells collected or on the duration of collection based on a multivariate linear regression analysis for association between receipt of >6 cycles of lenalidomide. In this retrospective analysis of MM patients undergoing autologous PBSC transplantation, we show that the duration of previous lenalidomide exposure does not impact the total number of PBSCs collected or the number of days of apheresis. These data suggest that longer courses of induction therapy with lenalidomide-containing regimens to achieve a maximum response can be safe without impairing the ability to collect PBSCs, and that limiting lenalidomide use before mobilization does not appear warranted in all cases.

Prolonged Lenalidomide Therapy Does Not Impact Autologous Peripheral Blood Stem Cell Mobilization and Collection in Multiple Myeloma Patients: A Single-Center Retrospective Analysis.

Clinical and cost outcomes of pre-emptive plerixafor administration in patients with multiple myeloma undergoing stem cell mobilization

765 Background: To assess the economic impact of the availability of ziv-aflibercept for patients with mCRC following disease progression after oxaliplatin, a user-adaptable budget impact model was...

Budgetary impact of adding ziv-aflibercept to a United States health plan formulary as a post-oxaliplatin biologic option for patients with metastatic colorectal cancer (mCRC).


 Introduction:
 Clinical trials have shown improved outcomes with direct-acting oral anticoagulant (DOAC)- vs. warfarin-based regimens in patients with atrial fibrillation (AF) with acute coronary syndrome and/or undergoing percutaneous coronary intervention (PCI). This study investigated the impact of anticoagulant type on hospital readmission rates following a myocardial infarction (MI) managed with PCI in patients with nonvalvular AF (NVAF) in the real world.
 
 
 Methods:
 This was a retrospective, observational study using data from two US claims databases, Optum
 ®
 Research and PharMetrics
 ®
 Plus. Patients with NVAF who were hospitalized for MI, underwent PCI between January 1, 2014 and December 31, 2020, and initiated treatment with warfarin or a DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) exclusively during the index hospitalization or ≤365 days after discharge were included. Once identified, patients were followed for up to 12 months post-discharge. Hospital readmission rates at 30, 90, 180, and 365 days were compared for DOACs vs warfarin using multivariate Cox proportional hazards modeling.
 
 
 Results:
 The Optum cohort included 2647 patients (1997 DOAC, 650 warfarin) and the PharMetrics cohort included 2056 (1468 DOAC, 588 warfarin). In both cohorts, unadjusted all-cause, stroke/systemic embolism (SE)-related, and bleed-related hospital readmission rates were lower for DOACs vs warfarin at all timepoints. Regression analysis showed a significantly lower risk of hospital readmission with DOACs vs warfarin (
 Table
 ).
 
 
 Conclusions:
 Real-world data from two large claims databases demonstrated that post-hospitalization DOAC treatment was associated with lower hospital readmission rates than warfarin treatment in patients with NVAF who were hospitalized for MI and underwent PCI. These results thus demonstrate the value of DOAC treatment for these patients.
 
 
 


Abstract 9496: Association Between Oral Anticoagulant Type and Hospital Readmission Rates Following Myocardial Infarction With Percutaneous Coronary Intervention in Patients With Nonvalvular Atrial Fibrillation

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Clinical and cost outcomes of pre-emptive plerixafor administration in patients with multiple myeloma undergoing stem cell mobilization

Budgetary impact of adding ziv-aflibercept to a United States health plan formulary as a post-oxaliplatin biologic option for patients with metastatic colorectal cancer (mCRC).

Abstract 9496: Association Between Oral Anticoagulant Type and Hospital Readmission Rates Following Myocardial Infarction With Percutaneous Coronary Intervention in Patients With Nonvalvular Atrial Fibrillation