Triple MAPK inhibition salvaged a relapsed post-BCMA CAR-T cell therapy multiple myeloma patient with a BRAF V600E subclonal mutation.

Background: Multiple Myeloma (MM) is a progressive plasma cell neoplasm characterized by heterogeneous clonal expansion. Despite promising response rates achieved with anti-BCMA CAR-T cell therapy, patients may still relapse and there are currently no clear therapeutic options in post-CAR-T settings. In this report, we present a case of a post-BCMA CAR-T relapsed/refractory (RR) MM patient with skin extramedullary disease (EMD) in which a novel MAPK inhibition combinatorial strategy was implemented based on next-generation sequencing and in vitro experiments.

A Focus on Newly Diagnosed Multiple Myeloma.

Multiple myeloma (MM) is an incurable plasma cell disorder that affects nearly 35,000 people annually. Over 149,000 individuals are estimated to live in the United States with MM. Research has generated a greater understanding of the pathology of this disease, now combined with mature clinical trial data that support the use of combination therapy in treatment.

Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma.

Daratumumab, a human immunoglobulin G1 kappa monoclonal antibody that targets CD38, is currently approved as monotherapy and in varying combinations with approved anti-myeloma regimens in both newly diagnosed multiple myeloma and relapsed refractory multiple myeloma. Originally developed for intravenous administration, the subcutaneous formulation of daratumumab (daratumumab and hyaluronidase-fihj) was recently approved by the US Federal Drug Administration and European Commission in 2020. In clinical trials, compared with the intravenous formulation, subcutaneous daratumumab (Dara-SC) has significantly shorter administration time (median first dose 7 h 3-5 min, respectively), lower rates of infusion-related reactions (median first dose 50% less than 10%, respectively), and lower volume of infusion (median 500-1000 ml 15 ml, respectively).

A phase II study of pomalidomide, daily oral cyclophosphamide, and dexamethasone in relapsed/refractory multiple myeloma.

Relapsed/refractory multiple myeloma patients treated with pomalidomide and dexamethasone have an overall response rate (ORR) of ∼30% and median progression-free survival (PFS) of 4-5 months. Previous studies explored addition of weekly cyclophosphamide, but we hypothesized that daily dosing allows for better synergy. We report the open-label, single-center phase II study of pomalidomide, daily cyclophosphamide and weekly dexamethasone (PCD).

A phase 2 study of panobinostat with lenalidomide and weekly dexamethasone in myeloma.

Phase 3 studies combining histone deacetylase inhibitors with bortezomib were hampered by gastrointestinal (GI) intolerance, which was not observed when combined with immunomodulatory drugs. This study is a single-center phase 2 study of panobinostat with lenalidomide and dexamethasone (FRD). Twenty-seven relapsed multiple myeloma patients were enrolled.

Heart and Lung Complications: Assessment and Prevention of Venous Thromboembolism and Cardiovascular Disease in Patients With Multiple Myeloma .

Background: Venous thromboembolism (VTE) and cardiovascular (CV) disease can occur in patients with multiple myeloma. Although VTE and CV disease are separate medical conditions, they can be serious and even life-threatening.
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Young Adults with Multiple Myeloma.

Objective: To identify the salient issues of young adults (YAs) diagnosed with multiple myeloma (MM), a hematologic disease of older adults, that is rare in patients 19-40 years of age.

Data Sources: Peer-reviewed journal articles, case reports, single-institution series, and national guidelines.

Conclusion: Compared to older adults with MM, YAs live longer and are at higher risk for survivorship-related issues, which include treatment adherence, infertility, reproductive concerns, risk of second primary cancers, treatment-related cardiotoxicity, and higher risk of non-cancer-related mortality.

Sex- and strain-related differences in first-pass alcohol metabolism in mice.

Adult males and females of three strains of mice, C57BL/10J, C57BL/6J and DBA/2J, were intubated or injected intraperitoneally with 0.02 ml/g body weight of a 25% alcohol solution. Thirty minutes later, their blood alcohol levels (BAL) were measured.