Clinical Management Guideline for Diffuse Large B Cell Lymphoma

Transcription

1 UNCONTROLLED WHEN PRINTED Prepared by: Dr David Meiklejohn Approved by: NOSCAN Haematology MCN 8 th May 2015 Issue date: 26 th May 2015 Review date: 26 th May 2017 Version: Page 1 of 11

2 Contents Page Pathological Diagnosis 3 Initial Evaluation 3 Management Special Consideration for those patients <18y Stage International Prognostic Index (IPI) and Revised IPI (R-IPI) Induction Therapy MYC +ve patients Radiotherapy Interim Restaging (post 3 rd or 4 th cycle) 6 Restaging at Completion of Treatment 6 Relapsed/refractory Disease 7 Systemic Anti-Cancer Therapy Definitions 8 References 11 Page 2 of 11

3 (includes Grade 3b Follicular Lymphoma) Pathological Diagnosis Review by member of regional lymphoma pathology group Immunophenotyping / Immunohistochemistry MYC re-arrangement testing (by FISH) FISH for relevant cytogenetic/molecular abnormalities Initial Evaluation Physical examination Performance status B symptoms FBC, U&E, LFT, Ca, urate LDH, B2 - microglobulin Hepatitis B, C and HIV ECG if indicated CXR if pulmonary involvement at diagnosis CT scan of neck, chest, abdomen & pelvis Depending on site of disease imaging of head and neck or MRI may be appropriate Bone marrow aspirate & trephine (could omit if baseline PET undertaken) Cardiac echo or MUGA scan (consider if >60 years, history of cardiac disease, hypertension, diabetes, heavy smoker) Lumbar puncture (LP) only if symptoms of CNS disease Management All patients should be discussed at an MDT Special consideration for those patients <18y Effective treatment of DLBCL and Burkitt /Burkitt-like lymphoma in this age group is available with a paediatric approach. Consideration for following a paediatric treatment protocol (FAB/LMB96 type approach using low dose anthracycline, ref 1) should be given to those <18y. Page 3 of 11

4 Stage I II III IV Localised, one nodal area Two or more nodal areas on the same side of the diaphragm Nodal disease on both sides of diaphragm (including spleen) Extranodal disease (including bone marrow involvement) Stage is suffixed with A or B depending on the absence or presence of B symptoms (fevers, drenching night sweats, weight loss of 10% body mass) International Prognostic Index (IPI) and Revised IPI (R-IPI) This should be recorded for all patients. Risk factors Age > 60 years Raised LDH Performance status 2 Ann Arbor stage 3 Two or more extranodal sites of disease IPI Risk factors (n) Risk category DLBCL 3yr OS 0-1 Low 91% 2 Low-intermediate 81% 3 High-intermediate 65% 4-5 High 59% R-IPI Risk factors Prognostic group 4 year PFS (%) 0 Good 94 1 or 2 Intermediate 80 3, 4 or 5 Poor 53 Page 4 of 11

5 Induction therapy Clinical Management Guideline for CNS prophylaxis recommended if: raised LDH + > 1 extranodal site involvement of following sites: testes, breast, epidural space, paraspinal mass, paranasal sinuses (see ref 2) intravascular B cell lymphoma (see ref 3) MYC +ve (ref 4) HIV +ve (Refer to separate CNS prophylaxis policy) Consider primary PEG GCSF prophylaxis (day 2) for patients >70yrs Stage 1A, no risk factors Stage 1A with risk factors (bulk 10cm, high LDH, extranodal site), IB, II-IV R-CHOP x 3 then IF radiotherapy R-CHOP x 6 Consider reduced dose doxorubicin or R-CEOP if impaired cardiac function (ref 5) If dose reduction being considered in elderly patients, consider R-miniCHOP (ref 6) MYC +ve patients Consider R CODOX-M/IVAC regimen in view of poor outcome with R-CHOP and high risk of CNS relapse (ref 4). If concerns re tolerability of this regimen, due to age/comorbidity Dose adjusted R-EPOCH is a reasonable alternative (ref 8). Radiotherapy In patients undergoing RT, this may be with either involved site or involved field RT In patients with stage IA disease receiving 6 cycles of chemotherapy, local radiotherapy may be considered in >60s with prior bulk disease, patients in whom salvage chemotherapy may not be feasible, patients receiving attenuated systemic chemotherapy Page 5 of 11

6 Interim restaging (post 3rd or 4th cycle) CT imaging Complete Response (CR) or Partial Response (PR) No Response (NR) or Progressive Disease (PD) Continue R-CHOP to total of 6 cycles (8 cycles no longer recommended, RICOVER study, ref 7) Change to salvage regimen (see below) Restaging at completion of treatment CT imaging Repeat other positive baseline studies Consider PET-CT if residual mass CR (including residual PET neg mass) PR with single PET positive mass NR, PD or PR with multiple PET positive masses Follow up as per separate policy Consider radiotherapy Salvage therapy or palliation In patients with a single PET +ve lesion, biopsy may be considered Page 6 of 11

7 Relapsed/refractory disease Fit patient Unfit patient R-IVE* x 3 or R-ESHAP* x 3 (if low albumin) Consider palliative chemotherapy (PECC or CEPP), radiotherapy or steroids Chemosensitive? Yes No BEAM autopbsct Consider palliative chemotherapy (PECC or CEPP), radiotherapy or steroids In patients with a single site of disease at relapse, radiotherapy may used as consolidation treatment after autologous stem cell transplant. *Rituximab should be omitted if primary refractory disease or progression within 6 months of Rituximab containing regimen. In selected cases there may still be a place for a GIANNI type approach in patients with true primary refractory disease. Page 7 of 11

8 Systemic Anti-Cancer Therapy Definitions 1. R-CHOP Rituximab 375mg/m 2 IV infusion Day 1 then Doxorubicin 50mg/m 2 IV Bolus Day 1 Vincristine 1.5mg/m 2 (max 2mg) IV Bolus Day 1 Cyclophosphamide 750mg/m 2 Bolus Day1 Prednisolone 50mg daily days 1-5 Repeated every 21 days 2. R-CEOP Rituximab 375mg/m 2 IV infusion Day 1 then Epirubicin 50mg/m 2 IV Bolus Day 1 Vincristine 1.5mg/m 2 (max 2mg) IV Bolus Day 1 Cyclophosphamide 750mg/m 2 Bolus Day1 Prednisolone 50mg daily days 1-5 Repeated every 21 days 3. R-miniCHOP Rituximab 375mg/m 2 IV infusion Day 1 then Doxorubicin 50mg/m 2 IV Bolus Day 1 Vincristine 1.5mg/m 2 (max 2mg) IV Bolus Day 1 Cyclophosphamide 750mg/m 2 Bolus Day1 Prednisolone 50mg daily days 1-5 Repeated every 21 days 4. CODOX-M IVAC including CNS prophylaxis Cyclophosphamide 800mg/m 2 IV infusion on day 1 and 200mg/m 2 infusion on Days 2 to 5 inclusive(4doses) Cytarabine 70mg/m 2 intrathecal injection days 2 and 4 Doxorubicin 40mg/m 2 IV bolus on day 1 Vincristine 1.5mg/m 2 (max 2mg) IV bolus on days 1 and 8 (2 doses) (cycle 3 days 1, 8 and 15 3 doses) Methotrexate 3000mg/m 2 infusion over 24 hours on day 10 Leucovorin 15mg/m 2 IV starting 36 hours after the start of IV Methotrexate 6 hourly ( if after 24 hours of completing methotrexate the patient is not being sick change to an oral dose) G-CSF from Day 13 until neutrophil count > /l Methotrexate 12.5mg/m 2 intrathecal injection day 15 Continue with this next stage when the patient s neutrophil count > /l Day1 = day of initiating this IVAC stage of the treatment should be completed as a separate protocol on CEPAS see next page Page 8 of 11

9 Ifosfamide 1500mg/m2 IV infusion days 1-5 (5 doses) Etoposide 60mg/m2 IV infusion days 1-5 (5 doses) Cytarabine 2000mg/m2 IV infusion 12 hourly days 1 and 2 (4 doses) Methotrexate 12.5mg/m 2 IT on day 5 G-CSF Day 7 until neutrophil count > /l 5. R-EPOCH Rituximab 375mg/m 2 IV infusion Day 1 then Etoposide 50mg/m 2 IV infusion on days 1-4 (4 doses) Prednisolone 60mg/m 2 orally days 1-5 (5 Days) Vincristine 0.4mg/m 2 IV continuous infusion days 1-4 Doxorubicin 10mg/m 2 IV continuous infusion days 1-4 Cyclophosphamide 750mg/m 2 IV infusions on day 5 Repeat every 21 days The instructions for dose adjustment are available at: appendix.pdf 6. R-IVE Rituximab 375mg/m 2 IV infusion Day 1 then Epirubicin 50mg/m 2 IV bolus Day 1 Etoposide 200mg/m 2 IV infusion day 1-3 (3 doses) Ifosphamide 3gm/m 2 IV infusion days 1-3 (3 doses) Repeated for up to three cycles 7. R-ESHAP Retuximab 375mg/m 2 IV infusion Day 1 then Etoposide 40mg/m 2 IV infusion on days 1-4 (4 doses) Methylprednisolone 500mg/m 2 IV infusion on days 1-4 (4 doses) Cisplatin 25mg/m 2 IV continuous infusion over 24 hours on days 1-4 (4 doses) Cytarabine 2g/m 2 IV infusion over 3 hours Day 5. Repeat after 21 days max three cycles 8. BEAM Carmustine (BCNU) 300mg/m 2 IV infusion on Day 1 Cytarabine 200mg/m 2 IV infusion twice daily Days 2-5 (8 doses) Etoposide Phosphate 200mg/m 2 IV infusion Days 2-5 (4doses) Melphalan 140mg/m 2 IV infusion Day 6 Stem Cell Return Day 7 9. PECC Prednisolone 40mg/m 2 orally daily Days 1-7 (7 doses) Etoposide 200mg/m 2 orally daily Days 1-3 (3 doses) Lomustine (~CCNU) 100mg/m 2 orally daily Day 1 Chlorambucil 20mg/m 2 orally daily Day 1-4 (4 doses) 10. CEPP Cyclophosphamide 600mg/m 2 IV infusion Day 1 and Day 8 (2 doses) Etoposide 70mg/m 2 IV infusion Day 1 Etoposide 140mg/m 2 orally days 2 and 3 (2 doses) Page 9 of 11

10 Procarbazine 60mg/m 2 Orally Days 1 to 10 (10 doses) Prednisolone 60mg/m 2 orally Days 1 to 10 (10 doses) Page 10 of 11

11 References Clinical Management Guideline for 1. Results of the Randomised International FAB/LMB96 Trial for Intermediate Risk B- Cell non-hodgkin Lymphoma in Children and Adolescents: It is Possible to Reduce Treatment for the Early Responding Patients. Patte C et al, Blood 2007; 109(7): Guideline on the prevention of secondary central nervous system lymphoma: British Committee for Standards in Haematology. McMillan A et al, Br J Haematol Oct;163(2): Central Nervous System Involvement in Intravascular Large B-Cell Lymphoma: a Retrospective Analysis of 109 Patients. Shimada K et al, Cancer Science, 2010, 101 (6), MYC Gene Rearrangements are Associated with a Poor Prognosis in Diffuse Large B-Cell Lymphoma Patients treated with R-CHOP Chemotherapy. Savage K et al. Blood, 2009, 114: R-CHOP with Etoposide Substituted for Doxorubicin (R-CEOP): Excellent Outcome in for Patients with a Contraindication to Anthracyclines. Moccia A et al, Blood, 2009, 114 (22): abstract Attenuated immunochemotherapy regimen (R-mini-CHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single arm, phase 2 trial. Peyrade F et al, Lancet Oncol, 2011, 12, Six versus Eight Cycles of Bi-weekly CHOP-14 with or without Rituximab in Elderly Patients with Aggressive CD20+ B-Cell Lymphomas: a Randomised controlled trial (RICOVER-60). Pfreundschuh M et al. Lancet Oncol 2008, 9 (2): Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. Donleavy K et al. NEJM 2013 Apr 11;368(15): Page 11 of 11