Management of Adverse Events Associated with Pomalidomide-Based Combinations in Patients with Relapsed/Refractory Multiple Myeloma.

Multi-agent regimens incorporating immunomodulatory (IMiD) agents such as thalidomide, lenalidomide, and pomalidomide have become the preferred standard of care for the treatment of patients with multiple myeloma (MM), resulting in improved survival outcomes. Currently, there are three IMiD agents approved for the treatment of MM: thalidomide, lenalidomide, and pomalidomide. Lenalidomide is commonly used to treat patients with newly diagnosed MM and as maintenance therapy following stem cell transplant or after disease relapse.

Impact of Black Race on Peripheral Neuropathy in Patients With Newly Diagnosed Multiple Myeloma Receiving Bortezomib Induction.

Purpose: The incidence of multiple myeloma (MM) is two to three times higher in Black patients compared with other races, making it the most common hematologic malignancy in this patient population. Current treatment guidelines recommend the combination of a proteasome inhibitor, an immunomodulatory agent, and a corticosteroid as preferred induction therapy. Bortezomib use comes with the risk of peripheral neuropathy (PN) and potential need for dose reduction, therapy interruption, and additional supportive medications.

Novel approaches to the treatment of multiple myeloma.

The treatment landscape for multiple myeloma (MM) has evolved significantly over the last decade with the approval of novel therapies and combinations in the newly diagnosed and relapsed/refractory settings. There has also been a shift toward a risk-adapted approach to induction and maintenance regimens, with the goal of achieving better response rates for those with high-risk disease. The incorporation of anti-CD38 monoclonal antibodies into induction regimens has led to longer progression-free survival and higher rates of measurable residual disease negativity.

Impaired SARS-CoV-2 Variant Neutralization and CD8+ T-cell Responses Following 3 Doses of mRNA Vaccines in Myeloma: Correlation with Breakthrough Infections.

Unlabelled: Patients with multiple myeloma (MM) mount suboptimal neutralizing antibodies (nAb) following 2 doses of SARS-CoV-2 mRNA vaccines. Currently, circulating SARS-CoV-2 variants of concern (VOC) carry the risk of breakthrough infections. We evaluated immune recognition of current VOC including BA.

Impact of concurrent gabapentin or pregabalin with high-dose melphalan in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplant.

Background: Melphalan is an alkylating agent used in both autologous (ASCT) and allogeneic stem cell transplantation. It is a substrate of L-type amino acid transporter-1 (LAT-1) and LAT-2, which are involved in its tissue penetration and elimination. Gabapentin and pregabalin, common concomitant medications in patients with multiple myeloma undergoing ASCT, are also substrates of LAT transporters, raising concern for potential competitive inhibition of melphalan transport.

Delayed allergic skin reactions to vaccines.

Recent advances in vaccination against the severe acute respiratory syndrome coronavirus 2 pandemic have brought allergists and dermatologists to the forefront because both immediate and delayed hypersensitivity reactions have been reported. This literature review focused on delayed reactions to vaccines, including possible causative agents and practical information on how to diagnose, evaluate with patch testing, and manage subsequent dose administration. Currently published reviews and case reports in PubMed, along with data on vaccines from the Centers for Disease Control and Prevention web site.

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations.

Objective: To review the available data for the efficacy and safety of daratumumab in the treatment of multiple myeloma (MM), both in the newly diagnosed and relapsed/refractory settings, as well as provide additional guidance to clinicians on operational, safety, and supportive care considerations.

Data Sources: A literature search of PubMed (1966 to October 2021) was conducted using the keywords , , and . Data were also obtained from prescribing information and unpublished abstracts from meetings.

Antibody treatment in multiple myeloma.

Antibody therapy, which has become a critical option in the treatment of multiple myeloma (MM), includes monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies. Anti-CD38 and anti-SLAMF7 monoclonal antibodies were the first to enter the MM portfolio as treatment options for relapsed/ refractory MM. More recently, daratumumab has become important in the treatment of newly diagnosed MM, and a subcutaneous formulation has been approved.

Current developments in the combination therapy of relapsed/refractory multiple myeloma.

Introduction: Therapy for patients with multiple myeloma has improved dramatically over the past decade following the introduction of novel agents and combinations across the disease spectrum. When relapse or refractory disease develops, non-cross-resistant drugs, most often used in multidrug regimens, have provided significant improvements in patient outcomes. Despite these advances, myeloma remains incurable and additional therapeutic approaches, based on emerging molecular and cellular biology, are moving rapidly through development phases.

Management of Mantle Cell Lymphoma in the Era of Novel Oral Agents.

To discuss (1) recent and emerging data for pharmacological management of untreated and relapsed/refractory (R/R) mantle cell lymphoma (MCL) with agents approved in the United States, (2) important considerations for toxicity monitoring and management, and (3) preliminary data and ongoing studies for agents in MCL-specific clinical trials. PubMed/MEDLINE, EMBASE, Google Scholar, product labeling, National Comprehensive Cancer Network, American Cancer Society, and ClinicalTrials.gov were searched for studies published between January 1, 2017, and January 31, 2020, and key historical trials.

Current and Investigational Agents Targeting the Phosphoinositide 3-Kinase Pathway.

Prevalent molecular alterations of the phosphoinositide 3-kinase (PI3K) pathway are found on solid tumors and are expressed in leukocytes, making it a desirable target in both solid and hematologic malignancies. In recent years, two agents targeting this pathway have been approved by the United States Food and Drug Administration, idelalisib and copanlisib, with many others under investigation. Due to the off-target effects seen with these agents, those under development have varying isoform specificity that mitigates toxicity.

Maintenance azacitidine after myeloablative allogeneic hematopoietic cell transplantation for myeloid malignancies.

Allogeneic hematopoietic cell transplantation (HCT) is a curative option for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), but carries a high risk of relapse. This retrospective review evaluates the effectiveness of maintenance azacitidine in high-risk AML and MDS patients to reduce the probability of relapse. Twenty-five patients who received maintenance azacitidine were matched to historical controls in a two-to-one ratio based on diagnosis, donor type, conditioning regimen intensity, and age.

Eosinophil Quantitated Urine Kinetic: A novel assay for assessment of eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic disease that requires long-term medical management and monitoring. The eosinophil count determined during esophageal biopsy remains the gold standard for diagnosis and monitoring of EoE. Although markers of eosinophil degranulation correlate with symptoms, eosinophil counts do not correlate.

Dinutuximab: An Anti-GD2 Monoclonal Antibody for High-Risk Neuroblastoma.

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, and formulary considerations for dinutuximab.

Data Sources: MEDLINE was searched (1964 to January 2016) using the terms ch14.18, dinutuximab, immunotherapy, and neuroblastoma.

Boron-based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal center.

We have used boron-based molecules to create novel, competitive, reversible inhibitors of phosphodiesterase 4 (PDE4). The co-crystal structure reveals a binding configuration which is unique compared to classical catechol PDE4 inhibitors, with boron binding to the activated water in the bimetal center. These phenoxybenzoxaboroles can be optimized to generate submicromolar potency enzyme inhibitors, which inhibit TNF-α, IL-2, IFN-γ, IL-5 and IL-10 activities in vitro and show safety and efficacy for topical treatment of human psoriasis.

Translational research involving oxidative stress and diseases of aging.

There is ample mounting evidence that reactive oxidant species are exacerbated in inflammatory processes, many pathological conditions, and underlying processes of chronic age-related diseases. Therefore there is increased expectation that therapeutics can be developed that act in some fashion to suppress reactive oxidant species and ameliorate the condition. This has turned out to be more difficult than at first expected.

Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis.

A series of phenoxy benzoxaboroles were synthesized and screened for their inhibitory activity against PDE4 and cytokine release. 5-(4-Cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2728) showed potent activity both in vitro and in vivo. This compound is now in clinical development for the topical treatment of psoriasis and being pursued for the topical treatment of atopic dermatitis.