Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study.

JCO We present 5-year outcomes from the phase 3 KEYNOTE-189 study (ClinicalTrials.gov identifier: NCT02578680). Eligible patients with previously untreated metastatic nonsquamous non-small-cell lung cancer without alterations were randomly assigned 2:1 to pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles with pemetrexed and investigator's choice of carboplatin/cisplatin for four cycles, followed by maintenance pemetrexed until disease progression or unacceptable toxicity.

First-Line Pembrolizumab Plus Chemotherapy for Advanced Squamous NSCLC: Real-World Outcomes at U.S. Oncology Practices.

Introduction: Pembrolizumab plus carboplatin and (nab-)paclitaxel (pembrolizumab-chemotherapy) is currently an approved and recommended systemic therapy for patients with previously untreated advanced squamous NSCLC. This retrospective study evaluated real-world time on treatment (rwToT) and overall survival (OS) among patients with advanced squamous NSCLC treated with first-line pembrolizumab-chemotherapy at oncology practices in the United States.

Methods: Using a real-world database, we selected adult patients with newly diagnosed or recurrent advanced squamous NSCLC (unresectable stages IIIB, IIIC, or IV) and good performance status (Eastern Cooperative Oncology Group 0-1) who initiated first-line pembrolizumab-chemotherapy from November 1, 2018, to May 31, 2020.

Pembrolizumab Plus Chemotherapy in Squamous Non-Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study.

JCO We report 5-year efficacy and safety outcomes from the phase III KEYNOTE-407 study (ClinicalTrials.gov identifier: NCT02775435). Eligible patients with previously untreated, metastatic squamous non-small-cell lung cancer (NSCLC) were randomly assigned 1:1 to pembrolizumab 200 mg or placebo plus carboplatin and paclitaxel/nab-paclitaxel once every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to 35 cycles.

Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma.

Purpose: PD-L1 is upregulated in glioblastoma and supports immunosuppression. We evaluated PD-L1 blockade with durvalumab among glioblastoma cohorts and investigated potential biomarkers.

Patients And Methods: MGMT unmethylated newly diagnosed patients received radiotherapy plus durvalumab (cohort A; n = 40).

Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407.

Introduction: Pembrolizumab plus chemotherapy significantly improved survival outcomes versus placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC in the randomized, double-blind, phase 3 KEYNOTE-407 study. We present the results of Chinese patients enrolled in the KEYNOTE-407 global and China extension studies.

Methods: Patients enrolled from mainland China in the KEYNOTE-407 global (NCT02775435) and China extension studies (NCT03875092) were randomized 1:1 to 35 cycles of pembrolizumab or placebo plus four cycles of carboplatin and paclitaxel or nab-paclitaxel.

A Prospective, Phase 1 Trial of Nivolumab, Ipilimumab, and Radiotherapy in Patients with Advanced Melanoma.

Purpose: Preclinical data suggest that radiotherapy (RT) is beneficial in combination with immune checkpoint blockade. Clinical trials have explored RT with single-agent immune checkpoint blockade, but no trials have reported RT with the combination of nivolumab and ipilimumab.

Patients And Methods: We conducted a phase 1 study of patients with stage IV melanoma receiving nivolumab and ipilimumab with two different dose-fractionation schemes of RT.

Ureidobenzenesulfonamides as efficient inhibitors of carbonic anhydrase II.

Sulfonamides represent an important class of drugs because of their inhibitory effect on carbonic anhydrases (CAs). We therefore synthesized several ureidobenzenesulfonamides and evaluated their bCA II inhibition for their potential use as anti-glaucoma gents. Since these compounds must not show cytotoxic effects, their cytotoxic potential against several human tumor cell lines and non-malignant fibroblasts was investigated.

Multicenter phase II study of a combination of cyclosporine a, methotrexate and mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow Transplant Cooperative Group (CBMTCG).

Background: Improvement of current GVHD prophylactic therapies remains an important goal in the allo-HSCT. We have described a novel prophylaxis regimen in a single institution trial. The Chinese Bone Marrow Transplant Cooperative Group (CBMTCG) initiated a phase II multicenter study.

Oncofetal antigen/immature laminin receptor protein in pregnancy and cancer.

The 37-kDa immature laminin receptor protein (iLRP) is a speciesconserved, universal immunogenic protein that is expressed in all thus-far examined embryonic and early fetal cells of inbred and outbred rodents. It has also been identified in human concepti. It is altered through normal maturation processes to become a non-immunogenic 67-kDa dimeric mature laminin receptor protein (mLRP) in mid-to late gestation in the mammalian fetus.

A phase 2 randomized trial of paclitaxel and carboplatin with or without panitumumab for first-line treatment of advanced non-small-cell lung cancer.

Introduction: This two-part phase 2 study evaluated the efficacy and safety of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, combined with carboplatin/paclitaxel in patients with previously untreated advanced non-small-cell lung cancer.

Methods: In part 1, patients were sequentially enrolled to receive paclitaxel 200 mg/m(2) and carboplatin (area under the concentration-versus-time curve, 6 mg/min/ml) plus panitumumab (1.0, 2.

Requirement of TPO/c-mpl for IL-17A-induced granulopoiesis and megakaryopoiesis.

IL-17A is a critical, proinflammatory cytokine essential to host defense and is induced in response to microbial invasion. It stimulates granulopoiesis, leading to neutrophilia, neutrophil activation, and mobilization. TPO synergizes with other cytokines in stimulating and expanding hematopoietic progenitors, also leading to granulopoiesis and megakaryopoiesis, and is required for thrombocytopoiesis.

CD34+ hematopoietic stem cells support entry and replication of poliovirus: a potential new gene introduction route.

Pluripotent hematopoietic stem cells (HSC) are critical in sustaining and constantly renewing the blood and immune system. The ability to alter biological characteristics of HSC by introducing and expressing genes would have enormous therapeutic possibilities. Previous unpublished work suggested that human HSC co-express CD34 (cluster of differentiation 34; an HSC marker) and CD155 (poliovirus receptor; also called Necl-5/Tage4/PVR/CD155).

Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis): a model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans.

Background: Hepatitis B virus (HBV) infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia) is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens.

Dose escalation of once weekly oral vinorelbine concurrent with weekly split dose hypofractionated chest radiation for palliation of advanced non-small cell lung cancer: a phase I/II study.

Introduction: Daily chest radiation schedules can be cumbersome for some patients and could also delay the administration of higher, systemic doses of chemotherapy.

Methods: Thirty-six patients with advanced non-small cell lung cancer (stages IIIB and IV) were treated using a once weekly hypofractionated chest irradiation schedule (5 Gy divided in 2 fractions 6 hours apart × 12 weeks), concurrently with escalating doses of oral vinorelbine.

Results: The maximum tolerated dose of vinorelbine was 80 mg/m; 28 patients were treated at 70 mg/m(2).

IL-17 is a potent synergistic factor with GM-CSF in mice in stimulating myelopoiesis, dendritic cell expansion, proliferation, and functional enhancement.

Objective: Interleukin (IL)-17, which now defines the Th(17) immune response, is a critical cytokine expressed and required for stress granulopoiesis during microbial invasion. Dendritic cells (DC) can instigate this response by inducing IL-17 expression in CD4(+) T cells. Besides IL-17, microbial invasion also stimulates production of the DC growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF).

Targeted agents for chronic myelogenous leukemia: will that be the end of allogeneic bone marrow transplantation for that disease?

Although the drug imatinib has been accepted as the treatment of choice for chronic myelogenous leukemia (CML) in chronic phase (CP) throughout the Western world, allogeneic stem cell transplantation (allo-SCT) continues to remain a widely practiced first-line treatment in countries with limited health care budgets. The rationale is not scientific, but largely economically based. We analyzed a cohort of 46 CML patients who participated in a graft-versus-host disease (GVHD) prophylaxis clinical trial and underwent related HLA-matched allogeneic peripheral blood stem cell transplantation.

Biochemical characterization of riboflavin carrier protein (RCP) in prostate cancer.

Riboflavin carrier protein (RCP) is a growth- and development-specific protein. Here, we characterized the expression of this protein in prostate cancer by polyclonal and monoclonal antibodies against chicken RCP. RCP was localized to both androgen-dependent and independent prostate cancer cell lines.

Production, safety and antitumor efficacy of recombinant Oncofetal Antigen/immature laminin receptor protein.

We describe here for the first time an efficient high yield production method for clinical grade recombinant human Oncofetal Antigen/immature laminin receptor protein (OFA/iLRP). We also demonstrate significant antitumor activity for this protein when administered in liposomal delivery form in a murine model of syngeneic fibrosarcoma. OFA/iLRP is a therapeutically very promising universal tumor antigen that is expressed in all mammalian solid tumors tested so far.

Combination of CsA, MTX and low-dose, short-course mycophenolate mofetil for GVHD prophylaxis.

In an effort to reduce the incidence and severity of acute GVHD (aGVHD), we have developed a new prophylaxis regimen combining cyclosporine and MTX with a short 30-day course of low-dose (500 mg per day) mycophenolate mofetil. This regimen was studied prospectively 100 patients undergoing HLA-matched and 1-antigen-mismatched allogeneic peripheral blood SCT from related donors. The cumulative incidence of aGVHD was 16% (grades II-IV (9.

IL-17F/IL-17R interaction stimulates granulopoiesis in mice.

Objective: IL-17F, a member of the interleukin (IL)-17 cytokine family, most closely resembles IL-17A structurally. IL-17A is a potent stimulator of granulopoiesis; its expression is induced in response to microbial challenge. Although IL-17F is considered to be a weak IL-17A analog that is also mediating its effect via IL-17R, its exact role and in vivo functions are unknown.

Phase I study of flavopiridol in combination with Paclitaxel and Carboplatin in patients with non-small-cell lung cancer.

Purpose: The aim of this study was to evaluate the safety and tolerability of escalating doses of flavopiridol/ paclitaxel/carboplatin in patients with advanced-stage non-small-cell lung cancer (NSCLC) as well as the pharmacokinetics and activity of flavopiridol when used in combination with paclitaxel/carboplatin.

Patients And Methods: Eligible patients aged 18-75 years with previously untreated stage IIIB/IV NSCLC received paclitaxel 175 mg/m2 over 3 hours followed by carboplatin area under the curve (AUC) 5 over 1 hour and flavopiridol 30-85 mg/m2 over 24 hours every 3 weeks for 3 cycles.

Results: Eighteen patients were enrolled at 4 sites in the United States and received flavopiridol 30 mg/m2 (n = 3), 50 mg/m2 (n = 6), 70 mg/m2 (n = 3), or 85 mg/m2 (n = 6).

Randomized phase III trial comparing bexarotene (L1069-49)/cisplatin/vinorelbine with cisplatin/vinorelbine in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT I.

Purpose: This study evaluated whether the combination of the synthetic rexinoid bexarotene with first-line cisplatin/vinorelbine therapy provides additional survival benefit in patients with advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Patients with stage IIIB with pleural effusion or stage IV NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to open-label bexarotene 400 mg/m(2)/d with cisplatin/vinorelbine or to cisplatin/vinorelbine alone. Antilipid agents were initiated on or before day 1 in the bexarotene arm.