Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial.

Purpose: Our preclinical studies showed that the oncolytic reovirus formulation pelareorep (PELA) has significant immunomodulatory anti-myeloma activity. We conducted an investigator-initiated clinical trial to evaluate PELA in combination with dexamethasone (Dex) and bortezomib (BZ) and define the tumor immune microenvironment (TiME) in patients with multiple myeloma treated with this regimen.

Patients And Methods: Patients with relapsed/refractory multiple myeloma (n = 14) were enrolled in a phase Ib clinical trial (ClinicalTrials.

Safety and efficacy of tenalisib in combination with romidepsin in patients with relapsed/refractory T-cell lymphoma: results from a phase I/II open-label multicenter study.

Tenalisib, a selective phosphoinositide-3-kinase δ/γ, and salt-inducible-kinase-3 inhibitor has shown efficacy and was well-tolerated in patients with T-cell lymphoma (TCL). In vitro studies suggest a synergistic anti-tumor potential for the combination of tenalisib with the histone-deacetylase inhibitor, romidepsin. This multicenter, open-label, phase I/II study was designed to characterize the safety, efficacy and pharmacokinetics of oral tenalisib twice-daily and intravenous romidepsin administered on days 1, 8 and 15 in 28-day cycles in adults with relapsed/refractory TCL.

A Versatile One-Step Competitive Fiber Optic Surface Plasmon Resonance Bioassay Enabled by DNA Nanotechnology.

Fiber optic surface plasmon resonance (FO-SPR)-based biosensors have emerged as powerful tools for biomarker detection due to their ability for real-time analysis of biomolecular interactions, cost-effectiveness, and user-friendliness. However, as (FO-)SPR signals are determined by the mass of the target molecules, the detection of low-molecular-weight targets remains challenging and currently requires tedious labeling and preparation steps. Therefore, in this work, we established a new concept for low-molecular-weight target detection by implementing duplexed aptamers on an FO-SPR sensor.

Variability in Cytogenetic Testing for Multiple Myeloma: A Comprehensive Analysis From Across the United States.

Purpose: Multiple myeloma (MM) treatment has changed tremendously, with significant improvement in patient out-comes. One group with a suboptimal benefit is patients with high-risk cytogenetics, as tested by conventional karyotyping or fluorescence in situ hybridization (FISH). Methodology for these tests has been published, but not necessarily standardized.

A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry.

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA.

Unrelated HLA mismatched microtransplantation in a patient with refractory secondary acute myeloid leukemia.

Microtransplantation (MST), a type of HLA-mismatched allogeneic cellular therapy, is a promising, cellular therapy for acute myeloid leukemia (AML). MST transfuses granulocyte colony-stimulating factor (G-CSF)-mobilized, HLA-mismatched donor peripheral blood stem cells into patients undergoing conventional chemotherapy. MST, using haploidentical donors, has been shown to yield clinical benefit without any permanent marrow engraftment in AML.

Pegaspargase-related high-grade hepatotoxicity in a pediatric-inspired adult acute lymphoblastic leukemia regimen does not predict recurrent hepatotoxicity with subsequent doses.

Pediatric acute lymphoblastic leukemia (ALL) regimens, including higher cumulative asparaginase doses, have been investigated in adult ALL to improve outcomes. Preliminary results are promising, but hepatotoxicity rates with long-acting pegaspargase are greater in adults than children. However, adult pegaspargase-related hepatotoxicity is not as clearly defined despite being the commonest adult toxicity.

HLA-Mismatched Microtransplant in Older Patients Newly Diagnosed With Acute Myeloid Leukemia: Results From the Microtransplantation Interest Group.

Importance: The outcome of older patients with acute myeloid leukemia (AML) remains unsatisfactory. Recent studies have shown that HLA-mismatched microtransplant could improve outcomes in such patients.

Objective: To evaluate outcomes in different age groups among older patients with newly diagnosed AML who receive HLA-mismatched microtransplant.

Phase I Study of Fenretinide Delivered Intravenously in Patients with Relapsed or Refractory Hematologic Malignancies: A California Cancer Consortium Trial.

A phase I study was conducted to determine the MTD, dose-limiting toxicities (DLT), and pharmacokinetics of fenretinide delivered as an intravenous emulsion in relapsed/refractory hematologic malignancies. Fenretinide (80-1,810 mg/m/day) was administered by continuous infusion on days 1 to 5, in 21-day cycles, using an accelerated titration design. Twenty-nine patients, treated with a median of three prior regimens (range, 1-7), were enrolled and received the test drug.

Asian-variant intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVLBCL) is a rare and deadly malignancy involving the growth of lymphoma cells within vessel lumina of all organ types. IVLBCL is further divided into the hemophagocytic Asian variant and a classical Western variant. Both variants are difficult to diagnose by imaging, and although diagnostic criteria have been developed to guide workup, histopathological examination remains imperative.

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

Background: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma.

Methods: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality.

Results: We found that variants in 7p15.

Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM.

In this proof-of-concept, open-label, phase 2 study, patients with relapsed/refractory multiple myeloma (RRMM) received elotuzumab with bortezomib and dexamethasone (EBd) or bortezomib and dexamethasone (Bd) until disease progression/unacceptable toxicity. Primary endpoint was progression-free survival (PFS); secondary/exploratory endpoints included overall response rate (ORR) and overall survival (OS). Two-sided 0.

Toxicity profile of repeated doses of PEG-asparaginase incorporated into a pediatric-type regimen for adult acute lymphoblastic leukemia.

Despite having been long regarded as too toxic for adult patients, pediatric-like regimens containing L-asparaginase have resulted in improved outcomes for adults with acute lymphoblastic leukemia (ALL). To characterize the spectrum of toxicity of repeated doses of polyethylene glycolated-asparaginase (PEG-asp) in adults, we reviewed all doses (2000 IU/m(2) ) administered as part of a pediatric-inspired regimen in adult ALL at our center. Subjects aged 18-60 yr with ALL (n = 152, 69.

Adding ascorbic acid to arsenic trioxide produces limited benefit in patients with acute myeloid leukemia excluding acute promyelocytic leukemia.

Arsenic trioxide (ATO) is highly effective in acute promyelocytic leukemia (APL), but despite its multiple mechanism of action, it has no activity in acute myeloid leukemia (AML) that excludes APL (non-APL AML). Ascorbic acid (AA) and ATO induces apoptosis in AML cell lines by depleting intracellular glutathione and generation of reactive oxygen species. In this study, we evaluated the effect of ATO plus AA in patients with non-APL AML.

Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia.

Purpose: Asparaginase treatment is standard in all pediatric acute lymphoblastic leukemia (ALL) regimens, whereas in adults, it is either excluded or administered for a shorter duration. Several adult ALL protocols are adapting pediatric regimens, but the optimal implementation of asparaginase is not well studied, considering its potential higher toxicity. We studied a pegaspargase dosing strategy based on its pharmacokinetic characteristics in adults.

An effective reinduction regimen for first relapse of adult acute lymphoblastic leukemia.

Current salvage regimens achieve complete remission (CR) in about a third of adults with relapsed/refractory acute lymphoblastic leukemia (ALL), and this represents a major barrier for performing allogeneic hematopoietic stem cell transplant (HSCT), the only potentially curative treatment. We conducted in adults with first relapse of ALL, a prospective clinical trial with intensive regimen derived from the pediatric Berlin-Frankfurt-Muenster-85 protocol, with addition of a continuous infusional multi-agent chemotherapy in phase II induction followed by consolidation with alternating monthly cycles. Objectives of this study included CR rate, leukemia-free survival (LFS) and toxicity of the regimen in adults.

Phase I trial of anti-CS1 monoclonal antibody elotuzumab in combination with bortezomib in the treatment of relapsed/refractory multiple myeloma.

Purpose: To evaluate the maximum-tolerated dose (MTD), safety, and efficacy of elotuzumab in combination with bortezomib in patients with relapsed or relapsed and refractory multiple myeloma (MM).

Patients And Methods: Elotuzumab (2.5, 5.

A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma.

This multicenter, first-in-human study evaluated the safety, tolerability, and pharmacokinetic and pharmacodynamic properties of the anti-CS1 monoclonal antibody elotuzumab. A standard 3 + 3 design was used to determine maximum tolerated dose; dose-limiting toxicities were assessed during cycle 1. Thirty-five patients with relapsed/refractory multiple myeloma were treated with intravenous elotuzumab at doses ranging from 0.

A phase I biological study of azacitidine (Vidaza™) to determine the optimal dose to inhibit DNA methylation.

This study aims to determine the optimal dosing and administration route for azacitidine to reduce global DNA methylation levels in the peripheral blood of patients with hematologic malignancies. Seventeen patients were enrolled into one of five dose level treatment groups (3 at 25 mg/m², 4 at 50 mg/m², 4 at 75 mg/m², 3 at 100 mg/m², and 3 at 150 mg/m²) and received IV azacitidine at their respective dose on days 1-5 of cycle one. All patients received 75 mg/m²/day IV on days 1-5 of cycle 2.

Pharmacokinetic and pharmacodynamic study of two doses of bortezomib in patients with relapsed multiple myeloma.

Purpose: Characterize bortezomib pharmacokinetics/pharmacodynamics in relapsed myeloma patients after single and repeat intravenous administration at two doses.

Methods: Forty-two patients were randomized to receive bortezomib 1.0 or 1.

Therapy-related, mixed-lineage leukaemia translocation-positive, monoblastic myeloid sarcoma of the uterus.

Myeloid sarcomas are tumour masses of myeloid leukaemic cells at extramedullary sites. These tumours can, on occasion, occur without concurrent or antecedent leukaemia. Myeloid sarcomas have been described at unusual locations including the female genital tract.