A. Janssens MD, PhD

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)

Highlights in chronic lymphocytic leukaemia & indolent non-Hodgkin lymphoma

(BELG J HEMATOL 2016;7(4):145–8)

BHS guidelines for the treatment of large granular lymphocyte and chronic prolymphocytic leukaemias

Summary

Large granular lymphocyte and prolymphocytic leukaemias are rare chronic lymphoproliferative disorders. Large granular lymphocyte leukaemias consist of indolent disorders such as T-cell large granular lymphocyte and chronic lymphoproliferative disorder of natural killer cells and the very rare but aggressive natural killer cell leukaemia. Treatment of the indolent large granular lymphocyte leukaemias is necessary in case of symptomatic cytopaenias or non-haematological autoimmune disorders. First line therapy of these two disorders is based on three immunosuppressive drugs: methotrexate, cyclophosphamide and cyclosporine A. Aggressive natural killer cell leukaemia needs an L-asparaginase containing regimen as induction followed by allogeneic stem cell transplantation to prolong remission. T-cell prolymphocytic leukaemia always follows an aggressive course even after an indolent onset. The optimal treatment strategy should exist of remission induction with alemtuzumab intravenously followed by autologous or allogeneic stem cell transplantation. Treatment indications for B-cell prolymphocytic leukaemia follow the criteria described by the chronic lymphocytic leukaemia guidelines. After induction with fludarabine, cyclophosphamide, rituximab or bendamustine in patients without a p53 mutation and/or a 17p deletion and alemtuzumab in case of a p53 mutation and/or a 17p deletion, stem cell transplantation must be considered.

(BELG J HEMATOL 2016; 7(3):103–11)

BHS guidelines for primary central nervous system lymphoma

Summary

Primary central nervous system lymphoma is a rare form of extranodal B cell lymphoma of the brain, the eyes, the meninges or the spinal cord in the absence of systemic lymphoma. The management of primary central nervous system lymphoma remains controversial, which is related to the rarity of the cases and the small number of controlled studies available. The present consensus report provides the guidelines proposed by the Belgian Hematology Society Lymphoproliferative Working Party for treating immunocompetent adult patients with primary central nervous system lymphoma.

(BELG J HEMATOL 2016;7(2):69–78)

Highlights in chronic lymphocytic leukemia

Summary

As new data on indolent non-hodgkin lymphoma (iNHL) were not that compelling, only highlights on chronic lymphocytic leukemia (CLL) will be presented in the following summary. The recently published “updated BHS guidelines for the treatment of CLL, anno 2016”, incorporated obinutuzumab, ibrutinib and idelalisib. Results of multiple plase 3 trials were presented at ASH 2015 and will probably challenge the proposed guidelines in the near future.¹

(BELG J HEMATOL 2016; 7(1):3–8)

Ibrutinib and idelalisib, the B-cell receptor antagonists available for use in daily clinical practice

summary

The first-in-class Bruton’s tyrosine kinase and phosphatidylinositol-3-kinase delta inhibitors have demonstrated impressive clinical activity and tolerability in several B-cell malignancies, both as single agent or in combination with rituximab. As reimbursement of ibrutinib and idelalisib by the Belgian national public health insurance has been granted, this review describes mechanism of action, dosage and administration, efficacy and tolerability. Although both molecules show a very favourable toxicity profile, treating physicians and patients must be aware of some medical events of interest.

(BELG J HEMATOL 2015;6(5):216–24)

Treatment of mantle cell lymphomas: Updated recommendations of the Belgian Hematological Society 2015

summary

Mantle cell lymphoma is a rare B-cell non-Hodgkin’s lymphoma characterised by a t(11;14) translocation resulting in overexpression of cyclin D1 and cell cycle dysregulation. Mantle cell lymphoma represents approximately 7–9% of all lymphomas in Europe.¹ Although new treatment regimens have improved the outcomes over the last decades, mantle cell lymphoma is still considered one of the worst prognosis B-cell non-Hodgkin’s lymphoma with a median overall survival of less than five years.² In September 2014 the Belgian Hematological Society recommendations for the treatment of mantle cell lymphoma were published.³ Since then, novel therapies such as ibrutinib and bortezomib have been approved by the European Medicines Agency in the treatment of mantle cell lymphoma. We present the new updated recommendations of the Belgian Hematological Society Lymphoproliferative Working Party. For young patients, the first line therapy remains an AraC-containing chemo-immunotherapy followed by high dose chemotherapy and autologous stem cell transplantation. For the main group of elderly patients, chemo-immunotherapy followed by maintenance with rituximab appears to be the gold standard. In relapse we can recommend treatment with BTK-inhibitor ibrutinib as first choice. Temsirolimus is reimbursed as third line treatment. Relapse patients should also be considered for allogeneic stem cell transplantation if eligible.

(BELG J HEMATOL 2015;6(5):203–8)