Zanubrutinib Versus Bendamustine and Rituximab in Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up of SEQUOIA.

JCO SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.

HLA-G can be transfered via trogocytosis from leukemic cells to T cells in chronic lymphocytic leukemia.

In chronic lymphocytic leukemia (CLL) immune escape mechanism allows leukemia cells to proliferate and expand and it might also be responsible for disease progression. Some molecules involved in the regulation of an immune system might represent prognostic value for CLL patients. Among numerous immune escape mechanisms it was shown that the expression of human leukocyte antigen G (HLA-G) might represent one of the agents damaging cellular immune response.

Mutations of ARID1B, PIK3C2B, KMT2B, and FAT1 genes influence clinical outcome in newly diagnosed myeloma.

The study aimed to elucidate the mutational profile of patients with newly diagnosed multiple myeloma to understand correlations of alterations with clinical outcomes. A cohort of 20 patients was enrolled, and mutational analysis was conducted using the TruSight Oncology 500 DNA Kit. Identified genetic alterations were related to clinicopathologic features and treatment outcomes.

Targeting splicing for hematological malignancies therapy.

Alterations in splicing patterns of leukemic cells have a functional impact and influence most cellular processes since aberrantly spliced isoforms can provide a proliferative advantage, enable to evade apoptosis, induce metabolic reprogramming, change cell signaling and antitumor immune response, or develop drug resistance. In this Review, we first characterize the general mechanism of mRNA processing regulation with a focus on the role of splicing factors, which are commonly mutated in blood neoplasms. Next, we provide a comprehensive summary on the current understanding of alternative splicing events, which confer resistance to targeted treatment strategies and immunotherapy.

Biological relevance of alternative splicing in hematologic malignancies.

Alternative splicing (AS) is a strictly regulated process that generates multiple mRNA variants from a single gene, thus contributing to proteome diversity. Transcriptome-wide sequencing studies revealed networks of functionally coordinated splicing events, which produce isoforms with distinct or even opposing functions. To date, several mechanisms of AS are deregulated in leukemic cells, mainly due to mutations in splicing and/or epigenetic regulators and altered expression of splicing factors (SFs).

Mass spectrometry-based assessment of M protein in peripheral blood during maintenance therapy in multiple myeloma.

Mass spectrometry (MS) can detect multiple myeloma-derived monoclonal proteins in the peripheral blood (PB) with high sensitivity, potentially serving as a PB assay for measurable residual disease (MRD). This study evaluated the significance of PB MS MRD negativity during posttransplant therapy in patients with newly diagnosed multiple myeloma. Serum samples from 138 patients treated in the phase 3 ATLAS trial of posttransplant maintenance with either carfilzomib, lenalidomide, and dexamethasone, or with lenalidomide alone were analyzed using EXENT MS methodology.

T-Cell Engagers-The Structure and Functional Principle and Application in Hematological Malignancies.

Recent advancements in cancer immunotherapy have made directing the cellular immune response onto cancer cells a promising strategy for the treatment of hematological malignancies. The introduction of monoclonal antibody-based (mAbs) targeted therapy has significantly improved the prognosis for hematological patients. Facing the issues of mAb-based therapies, a novel bispecific antibody (BsAb) format was developed.

Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS-CoV-2 similar to natural infection regardless ongoing treatments: A study by ERIC, the European Research Initiative on CLL.

Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies.

The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib.

Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response.

Polyclonal immunoglobulin recovery in patients with newly diagnosed myeloma receiving maintenance therapy after autologous haematopoietic stem cell transplantation with either carfilzomib, lenalidomide and dexamethasone or lenalidomide alone: Subanalysis of the randomized phase 3 ATLAS trial.

Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B-cell sequences in patients enrolled in the phase 3 ATLAS trial that randomized 180 subjects to either carfilzomib, lenalidomide, dexamethasone (KRd) or lenalidomide (R) maintenance. In the KRd arm, standard-risk patients with minimal residual disease negativity after six cycles de-escalated to R alone after cycle 8.

A Stepwise Screening Protocol for Multiple Myeloma.

Background: Monoclonal gammopathies and multiple myeloma should be screened in the primary care setting.

Methods: The screening strategy consisted of an initial interview supported with the analysis of basic laboratory test results and the increasing laboratory workload in the following steps was developed based on characteristics of patients with multiple myeloma.

Results: The developed 3-step screening protocol includes evaluation of myeloma-related bone disease, two renal function markers, and three hematologic markers.

Associations of and genes polymorphisms with central serous chorioretinopathy in a Greek population.

Background: Central serous chorioretinopathy (CSCR) is characterized by serous detachment of the central neurosensory retina and it is one of the most common retinal disorders. Various genetic polymorphisms have been associated with CSCR development.

Methods: The aim of our study was to investigate the potential association between (rs10490924) and (rs2070951 and rs5522) genes polymorphisms and CSCR development in a well defined Greek cohort for the first time in literature.

Molnupiravir is effective in patients with haematological malignancies.

Patients with hematologic malignancies are particularly vulnerable to severe infectious complications. SARS-CoV-2 infection is associated with a high risk of severe course and death in this patient population. In addition, immune deficits associated with both the blood cancer and the treatment used make vaccination against SARS-CoV-2 less effective than in immunocompetent individuals.

Carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone as maintenance therapy after autologous stem-cell transplantation in patients with multiple myeloma (ATLAS): interim analysis of a randomised, open-label, phase 3 trial.

Background: Lenalidomide is a cornerstone of maintenance therapy in patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation. We aimed to compare the efficacy and safety of maintenance therapy with carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone in this patient population.

Methods: This study is an interim analysis of ATLAS, which is an investigator-initiated, multicentre, open-label, randomised, phase 3 trial in 12 academic and clinical centres in the USA and Poland.

The role of NPM1 alternative splicing in patients with chronic lymphocytic leukemia.

Objectives: Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with heterogeneous clinical course. Recent studies revealed a link between NOTCH1 mutation and the overexpression of MYC and MYC-related genes involved in ribosome biogenesis and protein biosynthesis, such as nucleophosmin-1 (NPM1), in CLL cells. In the present study, we aim to evaluate the impact of the NOTCH1 mutation on the MYC and MYC induced NPM1 expression in CLL cells via quantification of their transcripts.

Secondary malignancies and survival of FCR-treated patients with chronic lymphocytic leukemia in Central Europe.

This is the first large-scale cross-country analysis of patients with chronic lymphocytic leukemia (CLL) aimed to evaluate the incidence, types, and key prognostic factors of secondary malignancies, and to assess the impact on overall survival based on retrospective claims data from three Central European countries. We analyzed 25,814 newly diagnosed CLL patients from Czechia, Hungary, and Poland; 10,312 (39.9%) patients were treated for CLL in study periods between 2004 and 2016.

Response to anti-SARS-CoV-2 mRNA vaccines in multiple myeloma and chronic lymphocytic leukemia patients.

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients have increased morbidity and mortality rates of COVID-19 due to immunosuppression associated with the disease and ongoing therapy. The same immune impairment accompanying CLL and MM also affects suboptimal vaccine response. The study assessed the effectiveness of the humoral and T cell-mediated immunity following mRNA COVID-19 vaccination (using either BNT162b2 or mRNA-1273) in short-term (2-5 weeks after second dose) and long-term follow-up (12 weeks after vaccination).

Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial.

Background: Zanubrutinib is a next-generation, selective Bruton tyrosine kinase inhibitor with efficacy in relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). We compared zanubrutinib with bendamustine-rituximab to determine its effectiveness as frontline therapy in patients with CLL or SLL.

Methods: We conducted an open-label, multicentre, phase 3 study at 153 academic or community hospitals in 14 countries and regions.

Programmed Cell Death-1 and Its Ligands as Targets for Therapy of Multiple Myeloma Patients.

Purpose: Among hematological malignancies, the expression profile of programmed cell death-1 (PD-1) and its ligands in multiple myeloma (MM) is still debated by numerous research groups. In current study, we characterized the expression of PD-1 and its ligands both on RNA and protein levels in MM patients. We have also attempted to analyze whether daratumumab therapy might overcome CD38-mediated immunosuppression that inhibits in particular CD8+ T-cell function.

Outcome of SARS-CoV-2-Infected Polish Patients with Chronic Lymphocytic Leukemia.

Background: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has become the cause of a worldwide pandemic, and its clinical infection course in patients with hematological malignancies may be severe.

Methods: We performed a retrospective study on 188 chronic lymphocytic leukemia patients (CLL) with COVID-19 infection.

Results: At the time of infection 51 patients (27.

Bendamustine-Based Regimens as Salvage Therapy in Refractory/Relapsed Multiple Myeloma Patients: A Retrospective Real-Life Analysis by the Polish Myeloma Group.

Multiple myeloma (MM) is an incurable disease and patients become refractory to the treatment in the course of the disease. Bendamustine-based regimens containing steroids and other agents are among the therapeutic options offered to MM patients. Here, we investigated the safety and the efficacy of bendamustine used in patients with refractory/relapsed MM (RRMM).

Avelumab in Combination Regimens for Relapsed/Refractory DLBCL: Results from the Phase Ib JAVELIN DLBCL Study.

Background: Relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis despite the availability of multiple treatment options. Preliminary evidence suggests that DLBCL may be responsive to programmed death ligand 1 (PD-L1)/programmed death 1 inhibitors.

Objective: The JAVELIN DLBCL study was conducted to assess whether a combination of agents could augment and sustain the antitumor immunity of avelumab, an anti-PD-L1 antibody, in R/R DLBCL.