REVIEW HEMATOLOGY

Stem cell-derived natural killer cell immunotherapy

SUMMARY

Natural killer cells are increasingly recognised as an attractive source of allogeneic immune effector cells in cancer immunotherapy. Over the past decade, several adoptive transfer trials using allogeneic NK cells from different sources have shown safety with little evidence of toxicities such as graft-versus-host disease, cytokine release syndrome or neurotoxicity that are often seen in T cell therapy. While clinical effects have been observed, improvements are warranted to increase relapse free survival and potentially cure cancer patients. Genetic engineering shows great potential for improving NK cell therapy through chimeric antigen receptors or knocking out immune checkpoints and MHC-I. Especially stem cell-derived natural killer cells are an ideal template as they can be cultured without T and B cell contamination and are relatively easy to genetically engineer compared to mature NK cells. Next to improving anti-tumour specificity, persistence can be improved by including cytokine domains in the chimeric antigen receptor, which is a great benefit over NK cell lines that need to be lethally irradiated to prevent uncontrolled proliferation. Importantly, the safety profile of adoptive NK cell transfer allows for minimal matching, which opens the door for large-scale production and cryopreservation to create an off-the-shelf therapy.

(BELG J HEMATOL 2020;12(2):59-65)

Tyrosine kinase inhibitor discontinuation in patients with chronic myelogenous leukaemia: A retrospective study and review of the literature

ABSTRACT

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with chronic myeloid leukaemia (CML). TKIs can be successfully discontinued in some CML patients who have achieved a stable deep molecular response.

OBJECTIVE: The purpose of this article is twofold. On the one hand, this review provides an overview of current use and discontinuation of TKIs in patients with CML. On the other hand, we retrospectively investigated the use and possible discontinuation of TKIs in a specific patient population with CML at the University Hospital of Leuven.

METHODS: A literature search was carried out in May 2019 to identify all relevant articles. Articles were searched on PubMed, Embase, Web of Science and Cochrane Library. Additionally, the articles found in the reference list were used.

RESULTS: This review included ten articles (two on imatinib, four on dasatinib, four on nilotinib), with 970 patients. Treatment free remission (TFR) ratio varied from 41–68% after one year. One study published the results of TFR after three years. In UZ Leuven, the TFR ratio was 60% after 106 weeks.

CONCLUSION: Tyrosine kinase inhibitor (TKI) therapy can be safely terminated in selected patient groups. About half of the patients retain the molecular remission after discontinuation of TKI therapy.

(BELG J HEMATOL 2020;12(2):52-8)

Monoclonal gammopathy of renal significance

SUMMARY

Monoclonal gammopathy of renal significance (MGRS) represents a heterogeneous group of diseases in which a monoclonal immunoglobulin, secreted by a plasma or B-cell clone with no evidence of malignancy, causes renal damage. As MGRS patients have a high risk of developing permanent kidney damage, adequate diagnosis and treatment are required to preserve kidney function. In this review, we address the definition, mechanisms and classification of MGRS, and discuss how patients with suspected MGRS should be evaluated and managed.

(BELG J HEMATOL 2020;11(8):376-80)

POEMS Syndrome

SUMMARY

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a rare disorder due to an underlying plasma cell clone (PC). The syndrome can affect several organs. The diagnosis is based on the presence of mandatory criteria (polyneuropathy, monoclonal plasma cell disorder) and at least one major and one minor criteria. The therapeutic regimen is determined according to the extent of the patient’s sclerotic lesions and the presence of bone marrow involvement.

(BELG J HEMATOL 2020;11(8):381-6)

BCMA targeting in multiple myeloma

SUMMARY

Over the past decade, significant progress was made in the treatment of patients with multiple myeloma (MM). Nevertheless, research efforts continue in an attempt to develop treatment options with novel mechanisms of action that have higher efficacy, can evade resistance to prior lines of treatment and are well tolerated. As the B-cell maturation antigen (BCMA) is preferentially expressed by mature B-lymphocytes and is overexpressed in MM patients, it provides an interesting therapeutic target in MM. Thus far, three treatment modalities have been developed for BCMA targeting; bispecific antibody constructs, antibody-drug conjugates and chimeric antigen receptor (CAR) T-cell therapy, each with its own advantages and challenges. This review provides an overview of the (preliminary) clinical data that were generated with these different treatment modalities.

(BELG J HEMATOL 2020;11(8):387-97)

State of the Art I: Venous thromboembolism

The first state of the art session of the 28^th annual BSTH meeting focussed on venous thromboembolism and was moderated by Alain Gadisseur and Kristel Vandenbosch. Prof. P-YLeRoux (physician in the department of Nuclear Medicine at the Brest University Hospital, France, and senior scientist in the Thrombosis Study group of Western Brittany) opened this session with a talk on the diagnosis of acute pulmonary embolism. Following up on this presentation, prof. dr. S. Konstantinides (Professor for Clinical Trials and Medical director of the multidisciplinary centre for thrombosis and haemostasis (CTH) at the University of Mainz, Germany and professor of Cardiology at the Democritus University of Thrace, Greece), turned the attention to the clinical management of pulmonary embolism.

State of the Art II: Immunothrombosis

The second state of the art session of the 2020 annual BSTH meeting focused on Immunothrombosis. First of all, Prof Adam Cunningham (University of Birmingham, UK) addressed the association between Salmonella infection and thrombosis, after which Assistant Prof. Kimberly Martinod (Catholic University Leuven, Belgium) discussed the role of neutrophil extracellular traps at the interface of thrombosis and inflammation. In a third and final lecture of the session, Dr. Frantzeska Frantzeskaki (Attikon University Hospital, NK University of Athens, Greece) turned the attention to immunothrombosis in patients with acute respiratory distress syndrome.