Lancashire and South Cumbria Haematology NSSG Guidelines for Follicular Lymphoma:

Transcription

1 1 Lancashire and South Cumbria Haematology NSSG Guidelines for Follicular Lymphoma: Pretreatment evaluation The following tests should be performed: FBC, U&Es, creat, LFTs, calcium, LDH, Igs/serum electrophoresis Beta-2-microglobulin Hepatitis B, C serology HIV serology following risk assessment CT scan neck, thorax and abdomen MRI scan for assessment of disease in the oropharynx and Waldeyer s ring, sinuses and nasal cavity, brain and paraspinal areas where there is a suspicion of spinal cord compromise Bone marrow aspiration and trephine biopsy where the findings are likely to influence management e.g a well patient with stage III low volume disease where initial management will be observation would not benefit. PET-CT scan should be considered to clarify whether a patient has early stage disease if initial IFRT is being considered or if there is a clinical concern that high grade transformation may have occurred. The FLIPI and FLIPI-2 scores must be calculated - note the nodal groups used to determine the score (see appendix 1). 1.2 Post treatment evaluation On completion of treatment the patient must be reassessed clinically and where treatment is given with curative intent all abnormal tests at baseline repeated followed by MDT discussion with review of an end of treatment CT scan. 2 Treatment 2.1 Stage IA and IIA with contiguous nodal disease Standard treatment should be IFRT 24Gy where involved nodes can be safely encompassed within a radiation field. Initial observation is an alternative option where there is concern regarding the potential toxicity of RT. There is no randomised comparison of IFRT and observation in such patients and long term treatment-free survival has been shown in those who did not receive RT. Hence observation is an alternative option, especially for older patients. 2.2 Advanced stage, asymptomatic low volume disease Definitions of low volume disease according to revised GELF criteria are given in appendix 2. Standard treatment should be observation. It is recognised that some patients may

2 2 prefer to have treatment and they should be managed as in Symptomatic advanced stage disease This will also apply to asymptomatic patients who do not meet the criteria for low volume disease. Initial treatment should be rituximab and chemotherapy. The optimal chemotherapy is unclear but generally CVP-R x 6-8 cycles or bendamustine-r x 6 cycles will be used. Obinutuzumab may be used in place of rituximab according to clinician preference CHOP-R x 6 cycles may be considered where there is bulky lymphadenopathy and a clinical suspicion of high grade transformation. Patients achieving at least PR should be offered maintenance rituximab (or obinutuzumab) every two months for two years. Chlorambucil +/- R or single-agent R are options for older patients and those with poor performance status and comorbidities. 2.4 Follicular lymphoma grade 3b Management is as for diffuse large B-cell lymphoma. 2.5 Relapsed and refractory follicular lymphoma Since there is a risk of transformation to high grade lymphoma rebiopsy should be performed where possible Treatment will generally be rituximab-chemotherapy IFRT should be considered for local disease control where relapse is dominated by disease at one site that can be safely encompassed within a radiotherapy field Patients achieving a second or third at least partial remission should be offered maintenance rituximab (or obinutuzumab after bendamustine-obinutuzumab) every three months for two years where maintenance was not given previously Consider consolidation with autologous or allogeneic stem cell transplant where the duration of last remission has been short i.e <2-3 years, and the patient is younger e.g <65 years, and lacks significant comorbidity The choice of chemotherapy will depend on several factors including age, FLIPI score at presentation, performance status and cardiac function, comorbidity, initial treatment and duration of response, potential for high dose therapy at this point or in the future, and availability of funding for new agents. The initial chemotherapy may be repeated if there was previously a good and prolonged response R-CHOP x 6 especially if consolidation with autologous or allogeneic stem cell transplant is being considered (alternatively R-IVE, R-ICE or R-DHAP depending on previous exposure to alkylating agents and/or anthracyclines)

3 3 Bendamustine-R If the patient did not respond or progressed during or up to 6 months after completing rituximab or rituximab-based chemotherapy consider bendamustineobinutuzumab followed by obinutuzumab maintenance every two months for two years Fludarabine-based treatment, either F-R or FC-R (avoid if potential transplant candidate) Bortezomib-R (not approved for funding at time of writing). Single agent rituximab is an option if the patient may not tolerate cytotoxic therapy Palliative chlorambucil or low dose etoposide +/- steroids where patients are heavily treated or frail and unlikely to tolerate other therapies 2.6 Transformed follicular lymphoma If they are anthracycline-naïve patients should receive R-CHOP x 6 cycles. The option of consolidation with autologous stem cell transplant should be discussed with younger fit patients. If they are unable to have anthracyclines salvage regimens as for relapsed DLBCL or gemcitabine should be used. Consolidation with high dose therapy and autologous or allogeneic stem cell transplantation should be considered in younger, fit patients who respond to chemotherapy. Note that consolidation with high dose therapy does not appear to benefit chemotherapy-naïve patients i.e discordant presentations with diffuse large B-cell and follicular lymphoma, and in patients with localised disease. Both these groups appear to have a better prognosis with chemotherapy alone +/- R

4 4 Appendix 1: FLIPI scores in follicular lymphoma Risk factors are: >60yrs, Hb < 12, stage III/IV, >4 nodal sites, raised LDH IPI %age of patients 10yr overall survival Low (0-1 factor) 36% 70.7% Intermediate (2 factors) 37% 51% High ( 3 factors) 27% 35.5% Nodal areas in the FLIPI Score (bilateral disease =2 points) Cervical: Mediastinal: Axillary: Mesenteric: Para-aortic: Inguinal: Other: Preauricular, upper cervical, median or lower cervical, posterior cervical, supraclavicular Paratracheal, mediastinal, hilar, retrocrural Coeliac, splenic, hepatic, portal, mesenteric Para-aortic, common iliac, external iliac Inguinal, femoral Epitrochlear, popliteal

5 5 FLIPI-2 score (Federico et al, 2009): 827 newly diagnosed patients treated for follicular lymphoma: 559 had rituximab, 49% had CHOP/CHOP-like chemo (73% of these with R), 8% had CVP (40% of these with R), 25% had fludarabine-based (71% with R), 4% had HD therapy. Median follow up 38 months. Excluded patients managed with watchful waiting Risk factors: High beta-2 micrglobulin, BM involvement, longest diameter of involved node >6cm, Hb < 12, age > 60yrs FLIPI-2 (all) N % PFS 3yrs OS 3yrs Low risk (0 factors) 20% 20% 91% 99% Intermediate risk (1-2 factors) 53% 69% 96% High risk (3-5 factors) 27% 51% 84% FLIPI -2 (treated with R) Low risk (O factors) 89% Intermediate risk (1 factor) 73% High risk (3-5 factors) 57% Appendix 2: Definitions of low volume disease in advanced follicular lymphoma 1. By revised GELF criteria low volume excluded if any of these are present: B symptoms ECOG performance status >1 Raised LDH B 2 microglobulin >3ug/ml Any nodal or extranodal mass with diameter >=7cm Involvement of >= 3 nodal sites each with a diameter of >3cm Marked splenomegaly Organ failure Pleural effusions or ascites Orbital or epidural involvement Peripheral blood infiltration Cytopenias i.e WBC <1.0, platelets < NCRI criteria in the watch and wait trial: Normal LDH Largest nodal mass < 7cm No more than 3 nodal sites with a diameter of 3cm or more No significant serous effusions clinically or on CT scan Splenomegaly <=16cm on CT scan

6 6 Author Ratified by LSCCN Haematology NSSG Dr MP Macheta 11 th Dec 2018 Review date: Dec 2019