T. Feys MBA, MSc

Highlights in myelodysplastic syndromes

Summary

In this article, a selection of interesting abstracts related to myelodysplastic syndromes (MDS) will be discussed. In lower-risk MDS, most attention goes to therapies that address anaemia. In this respect updated results of a phase III trial evaluating luspatercept were presented, while also the hydroxylase inhibitor roxadustat showed promising results. In addition to this, interesting data were presented on the restoration of erythropoietin sensitivity by lenalidomide. In higher-risk MDS, an abstract will be discussed looking at the optimal schedule for the administration of hypomethylating agents (HMA) next to a study evaluating the safety and efficacy of an oral HMA formulation. In addition to this, several new therapeutic options are being explored in higher-risk MDS. This includes combinations of novel agents (e.g. venetoclax, rigosertib, telaglenastat) with azacitidine and the use of targeted agents, specifically directed against mutations in MDS (e.g. olutasidenib, APR-246 and enasidenib).

(BELG J HEMATOL 2020;11(1):27–34)

Miscellaneous news from ASH 2019

Summary

In addition to the plethora of abstracts in the larger haematological subdomains discussed in this special issue of the BJH, ASH 2019 also featured many interesting presentations that do not fall within one of these categories. In this article we would like to address some of this ‘miscellaneous news’ from ASH 2019. In the field of venous thromboembolism (VTE), bodyweight-adjusted rivaroxaban could provide a new alternative treatment option for paediatric patients. Also with respect to VTE, the Ottawa score failed to demonstrate its predictive value for VTE recurrence in cancer patients. In addition, interesting new data were presented on the prevention of graft-versus-host-disease (GVHD) after an allogeneic transplantation. At this year’s meeting, there was also a session dedicated to disorders in the number or function of platelets in which much attention went to novel drug targets and novel drug combinations for the treatment of immune thrombocytopenia. Finally, some interesting presentations on sickle cell disease, myelofibrosis-associated anaemia and cold agglutinin disease (CAD) will be discussed in this overview.

(BELG J HEMATOL 2020;11(1):35–40)

Chimeric antigen receptor T-cells: a new therapeutic option for relapsed/refractory B-cell malignancies and beyond

Chimeric antigen receptor (CAR) T-cell therapy is a new cancer immunotherapy targeting specific cell surface antigens. This type of adoptive cell immunotherapy has been a breakthrough in the treatment of aggressive B-cell lymphoma and B-cell precursor acute lymphoblastic leukaemia (ALL) and is currently also being studied in other cancer types, including multiple myeloma and chronic lymphocytic leukaemia. This review will discuss the recent clinical developments and future perspectives of CAR T-cell therapy, with a focus on the clinical trials that led to the FDA and EMA approval of tisagenlecleucel (Kymriah®, Novartis) and axicabtagene ciloleucel (Yescarta®, Gilead) for the treatment of childhood/adult relapsed/refractory (r/r) B-cell precursor ALL and aggressive B-cell non-Hodgkin lymphoma.

(BELG J HEMATOL 2019;10(8):301–10)

Antibody-drug conjugates in the treatment of haematological malignancies

SUMMARY

Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with biologically active cytotoxic molecules or drugs. As such, they can deliver cytotoxic agents specifically at the tumour site in a way that minimises systemic exposure and its associated toxicity. As of 2001, four ADCs have been approved by the European Medicines Agency for multiple human malignancies: gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab emtansine, and inotuzumab ozogamicin. In addition to this, several new promising agents are under development. Although ADCs represent a new, effective class of therapeutics, the selection of the appropriate cytotoxin and linker remains challenging and systemic toxicity and rapid clearance should be monitored carefully. This review gives an overview on the safety and efficacy of ADCs in the treatment of haematological malignancies.

(BELG J HEMATOL 2019;10(8):311–9)

Bispecific T-cell engagers (BiTEs) in haematological malignancies

SUMMARY

Bispecific T-cell engagers (BiTEs) are a class of immunotherapeutics that can redirect T cells to haematological malignancies. A key advantage of BiTEs over adoptive T-cell therapies, consists of the fact that a BiTE is an “off the shelf” meaning that the same product can be given to all patients. In contrast, adoptive T-cell therapies must be made from cells taken from each patient and as a result this strategy is more time consuming and potentially more expensive. The most successful BiTE to date is blinatumomab. This agent is made up of CD3 and CD19 single-chain variable regions linked by a glycine–serine linker. It binds selectively to CD3 expressing T cells and CD19 expressing B cells, leading to the formation of immune synapses between T cells and B cells. In doing so, blinatumomab redirects unstimulated cytotoxic T cells to specifically target and lyse CD19-positive B cells. Blinatumomab is currently approved for patients with relapsed/refractory and minimal residual disease positive B-cell precursor acute lymphoblastic leukaemia (B-ALL). This review will discuss the pivotal trials with this agent and will touch upon some of the additional BiTEs that are under clinical evaluation in haematological malignancies. Finally, some remaining challenges with respect to optimising the efficacy and safety of BiTEs will be addressed.

(BELG J HEMATOL 2019;10(8):332–8)

New haematology reimbursements in Belgium

OVERVIEW OF BELGIAN REIMBURSEMENT NEWS

(BELG J HEMATOL 2019;10(6):258–60)

Highlights in aggressive lymphoma

SUMMARY

EHA 2019 featured several eagerly awaited presentations on Hodgkin lymphoma (HL). This included 3-year follow-up data of the ECHELON-1 trial in patients with high-risk features and longer follow-up data of CheckMate 2015 evaluating nivolumab plus doxorubicin, vinblastine, and dacarbazine in newly diagnosed advanced HL. In a third interesting HL abstract it was shown that foregoing radiotherapy in PET-negative patients with early-stage HL increases the risk of disease progression. In non-Hodgkin lymphoma (NHL), data were presented indicating that there is no benefit of rituximab maintenance beyond two years in patients with relapsed or refractory indolent NHL. In addition to this, interesting data were presented on the use of an obinutuzumab + DHAP combination in patients with untreated mantle cell lymphoma, with polatuzumab vedotin + obinutuzumab + lenalidomide in relapsed/refractory follicular lymphoma (FL) and with the anti-CD47 antibody Hu5F9-G4 in patients with refractory lymphoma.

(BELG J HEMATOL 2019;10(5):208–13)