SPECIALS

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)

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)

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)

Supportive care in multiple myeloma

SUMMARY

Patients with multiple myeloma (MM) not only require treatments directed at their disease activity, but also need a wide range of supportive measures. In this review article supportive measures with respect to anaemia, infections, thromboembolic risk, bone disease, peripheral neuropathy and pain are discussed.

Targeted therapies in multiple myeloma: new antibodies and CAR-T cells

SUMMARY

New therapeutic antibodies and T cells redirected to specific antigen targets with engineered chimeric antigen receptors (CARs) are emerging as powerful therapies in haematologic malignancies and multiple myeloma (MM). Various designs, manufacturing processes, and study populations, among other variables, have been tested and reported in clinical trials in MM. Here, we review and compare ongoing trials and the results of the reported clinical trials. We also discuss the outlook for CAR-T cell therapies, including managing toxicities and expanding the availability of personalized cell therapy as a promising approach to all haematologic malignancies.

Management of relapsed and refractory multiple myeloma patients

SUMMARY

For the majority of multiple myeloma (MM) patients, their disease will behave as a chronic disorder with episodes of remission followed by disease progression. Whereas the treatment approach in frontline is rather uniform, treatment at relapse has become more heterogeneous, as therapeutic choices at this stage are driven by many factors including disease characteristics and patient status, but also the previous treatment(s), their therapeutic effect and toxicities, and drug availability. With each treatment course patients also tend to become more vulnerable to hematological and non-hematological toxicities. Therefore, particularly at later relapses where there is no standard of care, the benefits and potential risks of therapeutic decisions should be carefully balanced in each individual patient, to minimize excess toxicities. In this review article, an overview is provided of the currently available treatment options for patients with relapsed or refractory MM.

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.