SPECIALS

The role of immunotherapy in the treatment of classic Hodgkin lymphoma

SUMMARY

Classic Hodgkin lymphoma (cHL) is one of the most frequent lymphomas in the Western world. Its incidence has a bimodal distribution with the most important peak arising in the age group of children and adolescents and a second less prominent peak in the elderly. Until recently, therapeutic options consisted solely of chemotherapy and/or radiotherapy. Despite the achievement of relatively high cure rates with these regimens, long-term toxicity remains a great concern. Moreover, patients that relapse or are refractory to these treatments generally have a poor prognosis despite the fact that autologous or allogeneic stem cell transplantation are options in fit patients. In the last decade, increased understanding of the pathobiology of Hodgkin lymphoma has led to the identification of several molecular targets for new therapeutic agents. Several of these molecules (i.e. brentuximab vedotin, nivolumab and pembrolizumab) have already proven their benefit in clinical trials and were subsequently approved by the US Food and Drug administration (FDA) and the European Medicine Agency (EMA) as safe and efficacious therapies for relapsed or refractory (R/R) cHL. Further results of randomised controlled trials (RCTs) are awaited to determine if these therapies also have a place in first-line. In the meantime, several other novel agents – ranging from checkpoint inhibitors to antibody-based drugs and cellular therapies – are being tested in clinical and preclinical studies. In this review we present an overview of the most important types of immunotherapies that are currently being used in the treatment of cHL or who demonstrated promising therapeutic potential.

(BELG J HEMATOL 2019;10(8):320–5)

Anti-CD38 monoclonal antibodies in the treatment of multiple myeloma

SUMMARY

As the surface antigen CD38 is highly expressed on malignant plasma cells, it provides an interesting therapeutic target for the treatment of multiple myeloma (MM). At present, three anti-CD38 monoclonal antibodies (mAb) have been studied in MM: daratumumab, isatuximab and MOR202. All three anti-CD38 mAb show complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibodydependent cellular phagocytosis (ADCP) activities. Moreover, immunomodulatory effects of daratumumab and isatuximab have been demonstrated. At present, daratumumab has been the most extensively studied anti-CD38 mAb in clinical trials. Following the excellent results of phase III clinical trials in relapsed/refractory MM (RRMM), daratumumab has recently also been studied in phase III clinical trials in newly diagnosed patients. The effects of isatuximab and MOR202 have been studied in phase III and phase I clinical trials, respectively, in patients with RRMM.

(BELG J HEMATOL 2019;10(8):326–31)

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)

Practical management of newly-diagnosed multiple myeloma: 2018 update for transplant eligible patients

SUMMARY

With the introduction of immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs), major improvements have been achieved in the treatment and outcome of multiple myeloma (MM). Different treatment combinations are now in use and newer therapies are being developed. Nevertheless, autologous stem cell transplantation (ASCT) remains the corner stone of therapy for fit, newly-diagnosed MM patients. Based on an extensive review of the recent literature, we propose recommendations on myeloma care, to be used by haematologists as a reference for daily practice.

Diagnosis and monitoring of multiple myeloma patients

SUMMARY

The diagnosis of multiple myeloma (MM) can be challenging, especially in patients with light-chain or non-secretory disease. The disease should be excluded in patients presenting with unexplained anaemia or renal failure and suspected in patients with signs of back pain combined with other systemic symptoms, such as fatigue and weight loss, or back pain combined with abnormal blood tests. The diagnosis is based on clinical, biological and radiological abnormalities that are resumed in the current article. At diagnosis, additional cytogenetic testing is important to determine the prognosis and guide physicians in their treatment choices. The disease is generally monitored by quantifying the monoclonal proteins in blood or urine. The follow-up of patients can be further tailored to the patients’ general status, obtained response and disease characteristics.

What is new in MGUS and smoldering multiple myeloma

SUMMARY

Multiple Myeloma (MM) and other plasma cell malignancies initially present as an asymptomatic precursor state, known as monoclonal gammopathy of undetermined significance (MGUS). When confronted to a monoclonal protein in blood or urine tests, physicians should first exclude the presence of a treatment-requiring MM. They should be aware that there are two benign precursor states, that do not require anti-myeloma treatment. Both MGUS and Smoldering Multiple Myeloma (SMM) need an initial visit by a haematologist, with further follow-up tailored to the individual patient and disease characteristics. In the current article we describe both entities, discuss their monitoring and resume the latest publications in their field.

First-line treatment of non-transplant eligible multiple myeloma patients

SUMMARY

Multiple Myeloma (MM) is mainly a disease of the elderly. In 2018 bortezomib-melphalan-prednisone (VMP) and lenalidomide-dexamethasone (Rd) are the established standard of care first-line regimens. Before starting therapy, an accurate evaluation of the frailty of patients is needed which allows physicians to individualize the approach for the individual patient.