CONGRESS NEWS

Adding elotuzumab to standard treatment for multiple myeloma delays disease progression

summary

Elotuzumab is a humanized antibody directed against signaling lymphocytic activation F7 (SLAMF7), a molecule that is selectively expressed on myeloma and natural killer (NK) cells but not on normal tissues. As a result, elotuzumab has a twofold mechanism: it enhances NK-cell activation directly via SLAMF7 and indirectly via CD16, and it induces targeted killing of SLAMF7-positive myeloma cells by antibody-dependent cellular cytotoxicity. In theory, these two effects collectively enable killing of myeloma cells without collateral damage to normal cells.^1–3 In an open-label, phase 1b/2 study, the combination of elotuzumab with len-dex resulted in high response rates and promising PFS findings. This formed the basis for the open-label, international, randomized, multicenter, phase III ELOQUENT-2 study, randomizing 646 patients with relapsed-refractory multiple myeloma (RRMM) who received 1–3 prior treatment lines to elotuzumab plus len-dex, or len-dex alone. The co-primary endpoints of the study were PFS and overall response rate (ORR), while OS, duration of response, quality of life and safety were secondary objectives.^4,5 The PFS and response data of this study were presented during the plenary session of the 2015 annual meeting of the European Hematology Association (EHA).

(BELG J HEMATOL 2015;6(3):114–5)

Carfilzomib-dexamethasone: a new ‘best in class’ in multiple myeloma

summary

While survival times have increased over the last decade, most patients with multiple myeloma eventually relapse and become refractory to therapy. The treatment of patients with relapsed and/or refractory multiple myeloma is frequently further complicated by the presence of pre-existing comorbidities that arise from an advanced disease state and toxicities stemming from prior anti-myeloma treatment. The advent of second-generation immunomodulatory drugs like pomalidomide and more recently, the second-generation proteasome inhibitor carfilzomib, have the potential to improve the outcome of these patients. During the 2015 annual meeting of the European Hematology Association (EHA), results of the phase III ENDEAVOR study, assessing the combination of carfilzomib with dexamethasone were presented.

(BELG J HEMATOL 2015;6(3):116–7)

Luspatercept increases hemoglobin and decreases the transfusion need in patients with low-, and intermediate-1 myelodysplastic syndrome

(BELG J HEMATOL 2015;6(3):118)

JAK2 inhibitor pacritinib significantly benefits patient reported outcomes in myelofibrosis

summary

The PERSIST-1 trial compares best available treatment (BAT) with the JAK2 inhibitor pacritinib in patients with myelofibrosis. During the 2015 EHA meeting in Vienna, Dr. Ruben Mesa (Mayo Clinic, Scottsdale, Arizona, US) presented the patient reported outcomes of this trial.

(BELG J HEMATOL 2015;6(3):119–20)

New treatment options for patients with inadequately controlled polycythemia vera

summary

Polycythemia vera (PV) is a rare and incurable blood cancer associated with an overproduction of blood cells in the bone marrow that affects roughly one to three people per 100,000 globally.¹ The disease is driven by the dysregulation of the JAK-STAT pathway.² It is typically characterized by elevated hematocrit, the volume percentage of red blood cells in whole blood, which can lead to a thickening of the blood and an increased risk of blood clots, as well as an elevated white blood cell and platelet count.² This can cause serious cardiovascular complications, such as stroke and heart attack, resulting in increased morbidity and mortality.³ Additionally, patients with PV may have an enlarged spleen and symptoms that are frequent and burdensome, with an overall impact on quality of life similar to that seen with myelofibrosis.⁴ PV is traditionally managed by phlebotomy, a procedure to remove blood from the body to reduce the concentration of red blood cells, which is used to help maintain a hematocrit level below 45%.³ However, phlebotomy is usually unsuitable as a permanent treatment option due to its inability to control symptoms or effectively manage the overproduction of red blood cells, therefore cytoreductive agents, such as hydroxyurea, may be added.³ Unfortunately, approximately 25% of patients with PV become resistant to or intolerant of hydroxyurea treatment according to ELN criteria, resulting in inadequate disease control and an increased risk of progression.⁵ Recent advances in the management of these patients with inadequately controlled PV formed the topic of a Novartis sponsored satellite symposium hosted during the 2015 annual meeting of the European Hematology Association (EHA).

(BELG J HEMATOL 2015;6(3):121–3)

Management of thrombosis in Paroxysmal Nocturnal Hemoglobinuria

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Thrombosis is a serious complication of paroxysmal nocturnal hemoglobinuria. At an EHA satellite symposium organized by Alexion Pharmaceuticals, dr. Anita Hill, hematologist and member of the National PNH Service in Leeds, UK, reviewed the past and current management of thrombosis associated with this rare disorder. The current article provides an impression of her presentation.

(BELG J HEMATOL 2015;6(3):124–6)

Polyphosphate, a modulator of hemostasis and thrombosis: a novel target for antithrombotic agents?

summary

The coagulation process that leads to haemostasis involves a complex set of reactions involving approximately 30 different proteins. These reactions convert fibrinogen to fibrin, which, together with platelets, forms a stable thrombus. It has long been known that the clotting cascade consists of two separate initial pathways (intrinsic and extrinsic) that ultimately converge into the ‘common pathway’. The intrinsic and extrinsic pathways essentially serve to activate the precursor protein prothrombin to the active enzyme thrombin, which in turns converts fibrinogen into fibrin. The intrinsic pathway includes the “contact” activation system. The way in which this pathway is activated is a matter of continued activation. It has long been known that artificial agents such as glass, clay, or ellagic acid are able to act as activators for this pathway, but only recently have real pathophysiologic activators been identified, including RNA, NETs and polyphosphate (PolyP). The biological function of the latter has long been unknown, but recent studies have begun to elucidate the roles of PolyP in regulatory and metabolic functions in humans.

(BELG J HEMATOL 2015;6(3):127–8)