Tandem high-dose influenza vaccination is associated with more durable serologic immunity in patients with plasma cell dyscrasias.

Patients with plasma cell dyscrasias (PCDs) experience an increased burden of influenza, and current practice of single-dose annual influenza vaccination yields suboptimal protective immunity in these patients. Strategies to improve immunity to influenza in these patients are clearly needed. We performed a randomized, double-blind, placebo-controlled clinical trial comparing tandem Fluzone High-Dose influenza vaccination with standard-of-care influenza vaccination.

Cost-Effectiveness of First-Line Versus Second-Line Use of Daratumumab in Older, Transplant-Ineligible Patients With Multiple Myeloma.

Purpose: The MAIA trial found that addition of daratumumab to lenalidomide and dexamethasone (DRd) significantly prolonged progression-free survival in transplant-ineligible patients with newly diagnosed multiple myeloma, compared with lenalidomide and dexamethasone alone (Rd). However, daratumumab is a costly treatment and is administered indefinitely until disease progression. Therefore, it is unclear whether it is cost-effective to use daratumumab in the first-line setting compared with reserving its use until later lines of therapy.

Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3, randomised, controlled trial.

Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is a standard therapy for newly diagnosed multiple myeloma. Carfilzomib, a next-generation proteasome inhibitor, in combination with lenalidomide and dexamethasone (KRd), has shown promising efficacy in phase 2 trials and might improve outcomes compared with VRd. We aimed to assess whether the KRd regimen is superior to the VRd regimen in the treatment of newly diagnosed multiple myeloma in patients who were not being considered for immediate autologous stem-cell transplantation (ASCT).

Differential effects of PD-L1 versus PD-1 blockade on myeloid inflammation in human cancer.

BACKGROUNDPD-1 and PD-L1 have been studied interchangeably in the clinic as checkpoints to reinvigorate T cells in diverse tumor types. Data for biologic effects of checkpoint blockade in human premalignancy are limited.METHODSWe analyzed the immunologic effects of PD-L1 blockade in a clinical trial of atezolizumab in patients with asymptomatic multiple myeloma (AMM), a precursor to clinical malignancy.

Integrated safety profile of selinexor in multiple myeloma: experience from 437 patients enrolled in clinical trials.

Selinexor is an oral, small molecule inhibitor of the nuclear export protein exportin 1 with demonstrated activity in hematologic and solid malignancies. Side effects associated with selinexor include nausea, vomiting, fatigue, diarrhea, decreased appetite, weight loss, thrombocytopenia, neutropenia, and hyponatremia. We reviewed 437 patients with multiple myeloma treated with selinexor and assessed the kinetics of adverse events and impact of supportive care measures.

Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma.

Background: Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options.

Methods: We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee.

Effect of leucovorin administration on mucositis and skin reactions in patients with peripheral T-cell lymphoma or cutaneous T-cell lymphoma treated with pralatrexate.

Peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) are rare, heterogeneous non-Hodgkin lymphomas with poor prognoses. Pralatrexate has demonstrated efficacy in T-cell lymphomas; however, mucositis has been reported as the most common dose-modifying adverse event. Leucovorin has been shown to minimize mucositis incidence, without sacrificing pralatrexate efficacy.

Early alterations in stem-like/resident T cells, innate and myeloid cells in the bone marrow in preneoplastic gammopathy.

Preneoplastic lesions carry many of the antigenic targets found in cancer cells but often exhibit prolonged dormancy. Understanding how the host response to premalignancy is maintained and altered during malignant transformation is needed to prevent cancer. In order to understand the immune microenvironment in precursor monoclonal gammopathy of undetermined significance (MGUS) and myeloma, we analyzed bone marrow immune cells from 12 healthy donors and 26 MGUS/myeloma patients by mass cytometry and concurrently profiled transcriptomes of 42,606 single immune cells from these bone marrows.

Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma.

Purpose Selinexor, a first-in-class, oral, selective exportin 1 (XPO1) inhibitor, induces apoptosis in cancer cells through nuclear retention of tumor suppressor proteins and the glucocorticoid receptor, along with inhibition of translation of oncoprotein mRNAs. We studied selinexor in combination with low-dose dexamethasone in patients with multiple myeloma refractory to the most active available agents. Patients and Methods This phase II trial evaluated selinexor 80 mg and dexamethasone 20 mg, both orally and twice weekly, in patients with myeloma refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide (quad-refractory disease), with a subset also refractory to an anti-CD38 antibody (penta-refractory disease).

Whole-exome sequencing in evaluation of patients with venous thromboembolism.

Genetics play a significant role in venous thromboembolism (VTE), yet current clinical laboratory-based testing identifies a known heritable thrombophilia (factor V Leiden, prothrombin gene mutation G20210A, or a deficiency of protein C, protein S, or antithrombin) in only a minority of VTE patients. We hypothesized that a substantial number of VTE patients could have lesser-known thrombophilia mutations. To test this hypothesis, we performed whole-exome sequencing (WES) in 64 patients with VTE, focusing our analysis on a novel 55-gene extended thrombophilia panel that we compiled.

Clinical and Serologic Responses After a Two-dose Series of High-dose Influenza Vaccine in Plasma Cell Disorders: A Prospective, Single-arm Trial.

Background: Patients with multiple myeloma (MM) and other plasma cell disorders are highly susceptible to influenza infections, which are major causes of morbidity in this population, despite the routine administration of a seasonal influenza vaccination. Existing data are limited by small and retrospective studies, which suggest poor seroprotection rates of < 20% after standard influenza vaccination in patients with MM.

Patients And Methods: Patients with plasma cell dyscrasia (n = 51) were treated with a 2-dose series of high-dose inactivated trivalent influenza vaccine during the 2014 to 2015 influenza season.

Chronic lymphocytic leukemia: prognostic factors and impact on treatment.

Chronic lymphocytic leukemia (CLL) is a clonal malignancy of mature B cells that displays immense clinical heterogeneity as reflected by the observation that many patients have an indolent disease that will not require intervention for many years while others will present with an aggressive and symptomatic leukemia requiring immediate treatment. Although there is no cure for CLL, the disease is treatable and current standard chemotherapy regimens have been shown to prolong survival. There is no obvious survival advantage to early treatment versus observation but the timing as to when a patient will require treatment is highly unpredictable.