CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial.

Chimeric antigen receptor (CAR) T cells targeting CD19 or CD22 have shown remarkable activity in B cell acute lymphoblastic leukemia (B-ALL). The major cause of treatment failure is antigen downregulation or loss. Dual antigen targeting could potentially prevent this, but the clinical safety and efficacy of CAR T cells targeting both CD19 and CD22 remain unclear.

Daratumumab plus lenalidomide and dexamethasone lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX.

In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death lenalidomide/dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.

Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma.

Daratumumab plus pomalidomide and dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with ≥2 prior lines of therapy who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary end point.

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.

Background: Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma.

Methods: In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival.

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma.

Daratumumab, a human CD38 immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day orally on days 1-21 of each cycle) and dexamethasone (40 mg/week).

Impact of cytochrome P450 3A4 inducer and inhibitor on the pharmacokinetics of trabectedin in patients with advanced malignancies: open-label, multicenter studies.

Purpose: To evaluate the pharmacokinetics, safety and survival of trabectedin, metabolized primarily by cytochrome P450 (CYP)3A4 enzyme, when coadministered with rifampin (CYP3A4 inducer) or ketoconazole (CYP3A4 inhibitor) in adult patients with advanced solid tumors.

Methods: Two phase 1/2a, 2-way crossover studies were conducted. For rifampin study, 12 patients were randomized (1:1) to sequence of a cycle of trabectedin (1.

Refining docetaxel-containing therapy for gastric cancer.

Gastric cancer-the second most common cause of cancer-related deaths worldwide-is a global health problem. Most cases present at advanced stages and are incurable due to locally advanced or metastatic disease. Although advanced gastric cancer is relatively chemosensitive, a gold standard chemotherapy regimen has yet to emerge, and response rates are of short duration.

Emerging roles for mammalian target of rapamycin inhibitors in the treatment of solid tumors and hematological malignancies.

Purpose Of Review: The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and survival in mammalian cells. mTOR pathways are frequently dysregulated in various malignancies, providing targets for new anticancer drugs and therapeutic strategies. Here, we summarize the clinical experience of trials using the first generation of mTOR inhibitors, the rapalogs, and highlight the development of the next generation of catalytic inhibitors of the pathway.

Microarray analysis of prostate cancer progression to reduced androgen dependence: studies in unique models contrasts early and late molecular events.

Three unique variants of the CWR22 human prostate cancer xenograft model (CWR22LD1, LD2, and LD3) with a decrease in dependence on androgens were selected under noncastrate conditions, i.e., by outgrowth after transplantation into male NCR (AT) nu mice without testosterone supplementation.

10-propargyl-10-deazaaminopterin: an antifolate with activity in patients with previously treated non-small cell lung cancer.

Purpose: 10-propargyl-10-deazaaminopterin (PDX) has superior antitumor efficacy in mouse xenograft models, likely attributable to increased uptake by the RFC-1 folate transporter and greater intracellular polyglutamylation. In a previous Phase I trial, stomatitis was the dose-limiting (and only clinically significant) toxicity of PDX. The recommended Phase II dose was 150 mg/m(2) i.

Despite some expression of folate receptor alpha in human mesothelioma cells, internalization of methotrexate is predominantly carrier mediated.

Objective: As a response to a published report documenting some expression of folate receptor alpha in human mesothelioma, studies were carried out examining the role of this receptor versus that of the reduced folate carrier in the internalization of folate analogs in this neoplasm.

Methods: Influx measurements of tritiated methotrexate were carried out in 4 mesothelioma cell lines, and 2 additional cell lines were used as comparators. Relative gene-expression analysis for the carrier and receptor gene was done by using real-time reverse transcriptase-polymerase chain reaction in the above-mentioned cell lines and mesothelioma tumor tissues obtained from patients.