A. Janssens MD, PhD

Venetoclax, the first available bcl-2 antagonist for chronic lymphocytic leukaemia

SUMMARY

Venetoclax, the first-in-class bcl-2 antagonist, has demonstrated deep and durable remissions as a single agent in relapse/refractory chronic lymphocytic leukaemia patients with a 17p deletion or chronic lymphocytic leukaemia refractory to B-cell receptor inhibitors or progressive after B-cell receptor inhibitor discontinuation. As reimbursement of venetoclax by the Belgian national public health insurance has been provided, this review describes mechanism of action, dosage and administration, efficacy and tolerability. As venetoclax can rapidly reduce the chronic lymphocytic leukaemia load, precautions to avoid tumour lysis syndrome depending on risk assessment is a sine qua non. Despite the convenience afforded by this oral, once daily formulation, treating physicians and patients must be aware of drug adherence and drug-drug interactions which can challenge treatment benefits and risks.

(BELG J HEMATOL 2017;8(7):265–71)

CNS prophylaxis in aggressive non-Hodgkin’s lymphoma

SUMMARY

Although it doesn’t occur frequently, central nervous system relapse in aggressive non-Hodgkin lymphoma carries a very dismal prognosis. Indications for the use of prophylactic strategies are clear-cut in Burkitt and lymphoblastic lymphoma. However, this remains subject to much debate in other types of aggressive non-Hodgkin lymphoma, like diffuse large B-cell lymphoma. Available strategies consist of intrathecal administration of chemotherapy, the systemic use of high-dose central nervous system-penetrating cytotoxic agents or a combination of both. Nevertheless, all known methods entail a certain risk for toxicity in patients. Hence, great effort has been put in the search for risk factors and scores to identify high-risk patients who have benefit from central nervous system-prophylaxis and to exclude those who do not. This article aims to provide an overview of existing strategies, pharmacological properties and side effects of available cytotoxic agents, as well as an update on the current guidelines for the implementation of central nervous system prophylaxis in different types of non-Hodgkin lymphoma. However, due to lack of qualitative prospective data, a golden standard in this field is still lacking.

(BELG J HEMATOL 2017;8(6):232–8)

BHS guidelines for the diagnosis and the treatment of hairy cell leukaemia

SUMMARY

Hairy cell leukaemia is a rare chronic B-cell lymphoproliferative disorder characterised by a long natural course with, in most of cases, an excellent response to a single course of purine analogue monochemotherapy. Making the right diagnosis, excluding the chemo resistant variant form of hairy cell leukaemia, and making progresses in the treatment of relapsing and/or refractory disease remains challenging up to date. In recent years, exciting results with new agents are emerging and clinical trials are ongoing to optimize the management of hairy cell leukaemia and its variant form.

(BELG J HEMATOL 2017;8(6):222–8)

Highlights in chronic lymphocytic leukemia

SUMMARY

This report will summarize useful clinical updates for the management of chronic lymphocytic leukemia (CLL) presented during the biannual International Workshop on Chronic Lymphocytic Leukemia (iwCLL, New York, May 12–15 2017), the 2017 International Conference on Malignant Lymphoma (ICML; Lugano June 14–17) and the 2017 annual meeting of the European Hematology Association (EHA; Madrid June 22–25).

(BELG J HEMATOL 2017;8(4):129–32)

P15 Treatment patterns of Waldenström’s macroglobulinemia in Belgium

P37 CD123 expression on acute leukemia blasts, hematogones, and monocytes; used as Minimal Residual Disease Marker

Highlights in CLL and low-grade lymphoma

SUMMARY

Immunochemotherapy induction followed by maintenance with rituximab (R) is the standard of care (SoC) for patiens (pts) with advanced-stage symptomatic follicular lymphoma (FL), achieving a median progression free survival (PFS) of 6–8 years (yrs) and a median survival (OS) of 12–15 yrs. However, FL is incurable and most pts eventually relapse. Relapse occurs in 30% of pts within 3 yrs, and is associated with a poor prognosis. Obinutuzumab (G) is a glycoengineered type II anti-CD20 monoclonal antibody with enhanced direct cell killing and antibody-dependent cellular cytotoxicity. Promising activity and manageable toxicity when combined with chemotherapy has already been shown in treatment-naïve chronic lymphocytic leukemia (CLL) (G-chlorambucil (Chl)) and in R-refractory indolent non-Hodgkin lymphoma (iNHL). We waited eagerly for the results of GALLIUM, the phase 3 trial which compared G-chemo to R-chemo in advanced, untreated FL. Treatment options for pts with refractory iNHL are limited. Last year, the phase 3 GADOLIN trial, comparing the efficacy and safety of G-bendamustine (B) induction, followed by G maintenance (G-B arm), with B induction (standard in R-refractory iNHL pts), already showed a gain in PFS and time to next treatment (TTNT) for the G-B arm. At this years ASH meeting we learned whether longer follow-up would also show a survival benefit. In previous yrs the outcome of multiple phase 2 and 3 trials with oral B-cell receptor (BCR)-inhibitors in treatment-naïve and relapsed/refractory (R/R) CLL were reported, which led to the approval of these agents for the treatment of CLL. This led to a shift from intravenous chemotherapies, given for a finite number of cycles, to oral therapies given continuously until progressive disease or unacceptable toxicity. Follow-up of these trials is necessary to evaluate long-term efficacy in pts with different prognostic factors and long-term safety.

(BELG J HEMATOL 2017;8(1):23–8)