Guidelines for the Treatment of Diffuse Large B Cell Lymphoma (DLBCL) Author: Dr Barrie Woodcock On behalf of the Haematology CNG (Previous version has been revised) Agreed at CNG: January 2012 Review Due: January 2013 MCCN guidelines for treatment of diffuse large B cell lymphoma (DLBCL) January 2012 For review January 2013 Page 1 of 7 MCCN Guidelines for treatment of Diffuse Large B Cell Lymphoma (DLBCL) All patients should be considered for, and offered, NCRN/ MRC clinical trials at diagnosis and relapse. Scope: The following applies to those patients with DLBCL except : Exclusions : Primary CNS lymphoma DLBCL skin follicle centre cell type Intraocular lymphoma Diagnosis: Diagnosis made on adequate tissue biopsy according to current MCCN Haematopathology guidelines. FISH for myc gene rearrangements may be performed if the clinician will alter therapy if myc rearrangements are present. Risk Stratification and Outcome (Revised IPI): Revised IPI (patients receiving RCHOP)1 Risk factors Age > 60 years PS >2 Raised LDH Stage 3 and 4 >1 extranodal site Outcomes with therapy (4 year PFS, 4 year OS) No risk factors 1 - 2 risk factors 3 - 5 risk factors PFS OS 94% 80% 53% 94% 79% 55% MCCN guidelines for treatment of diffuse large B cell lymphoma (DLBCL) January 2012 For review January 2013 Page 2 of 7 Staging and Assessment: Performance status FBC, U+E, LFT, Bone LDH CTscan - Neck thorax , abdomen, and pelvis MR scan for lymphoma of head and neck, bone or epidural PET/CT scan recommended if PETCT to be used for final staging post therapy. Depending on quality this may substitute for the standard CT (discuss with provider) LP : testicular, paranasal sinus and epidural Echocardiogram (age >60years, diabetes, known heart disease, hypertension) HIV Hepatitis B and C Bone Marrow Biopsy Therapy: The basis of therapy is RCHOP. In the presence of inadequate cardiac function substitute RCEOP for RCHOP2 A prechemotherapy phase of 100mg Prednisolone per day for 7 days (as occurs in the DSHNL studies) is now widely advocated for those patients with increased performance status or symptoms and should be considered. The use of 1mg Vincristine has now been dropped from the DSHNL studies. Limited Stage Disease: IA and IIA limited to an area encompassed by one radiotherapy treatment area : A choice of treatments based on patient’s views, convenience and consequences of radiotherapy (eg salivary gland involvement or breast involvement in a young woman) RCHOP 21 x 3 plus involved field radiotherapy Or RCHOP x 6 Restage post therapy with CT or PETCT 6 weeks post therapy. MCCN guidelines for treatment of diffuse large B cell lymphoma (DLBCL) January 2012 For review January 2013 Page 3 of 7 Testicular Disease: Systemic chemotherapy (RCHOP14 or RCHOP 21 x 6) with CNS prophyhlaxis and radiotherapy to testis after completion of chemotherapy. Disseminated Disease: Without adverse prognostic features : Either : RCHOP 21 (6 cycles RCHOP ) (as per control arm of REMODEL-B) Or RCHOP 14 Assess response after completion of therapy (see REMODEL-B). PETCT should be performed 6 weeks after completion of therapy With Adverse features (3-5 risk factors) and physically fit for therapy: RCHOP 21 (6 cycles of RCHOP) Or RCHOP 14 Or Investigational therapy – NCRN trial R-CODOXM/IVAC or REMODEL-B Or PBSCT after completing chemotherapy3 Myc gene rearrangements4 to be tested if directed by haematologist with a view to offering more intensive therapy. If present the clinician may elect to alter therapy to R-CODOXM/IVAC Assess response at the end of therapy or before if indicated If using PETCT this should be done 6 weeks after completion of therapy. MCCN guidelines for treatment of diffuse large B cell lymphoma (DLBCL) January 2012 For review January 2013 Page 4 of 7 PETCT result at the end of therapy: It is recommended that biopsy is used to confirm resistant disease in PET positive patients If limited to one site of active, confirmed disease radiotherapy should be given. CNS prophylaxis: Prophylaxis is given as: Intrathecal Methotrexate given with the first 3 to 6 cycles of therapy, (see REMODELB) one given with each cycle; total of three injections - in the following situations: Mandatory: DLBCL of Testis Intravascular B cell lymphoma has a high (33%) tendency to relapse in the CNS and some form of prophylaxis is recommended. In the absence of evidence physician choice is appropriate. The pathology of this disease may suggest that systemic high dose methotrexate is appropriate. Options for CNS prophylaxis: RCHOP 14 and no prophylaxis5 Prophylaxis for high risk groups – choice of a. High LDH and 2 or more extranodal sites b. Consider for orbit, bone marrow, peripheral blood, epidural, or nasal/ paranasal sinuses (REMODEL-B suggests patients in these groups should receive prophylaxis at the investigator’s discretion). Management of the Over 80’s: There is no randomised evidence as to dose intensity and this is often made by physician choice. The recent publication from the GELA6 is not randomised but describes very good results using 50% dose reduction in the chemotherapy part of the treatment (cyclophosphamide, doxorubicin, vincristine). MCCN guidelines for treatment of diffuse large B cell lymphoma (DLBCL) January 2012 For review January 2013 Page 5 of 7 Relapse: Investigation as at diagnosis. Fit for autologous PBSCT: RICE or RDHAP x 3 plus PBSCT Or ORCHARRD – Relapsed/Refractory DLBCL:Comparison of “O” vs “R” + salvage regime prior to autotransplant. (NCRN adopted). (when open) Unfit for autologous PBSCT: Physician choice with palliative Radiotherapy for limited relapse. Second Relapse: Fit for allogeneic PBSCT – discuss with transplant centre and consider appropriate chemotherapy followed by allogeneic PBSCT MCCN guidelines for treatment of diffuse large B cell lymphoma (DLBCL) January 2012 For review January 2013 Page 6 of 7 References: 1. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Laurie H. Sehn, Brian Berry, Mukesh Chhanabhai et al Blood. 2007;109: 1857-1861 2. 408 R-CHOP with Etoposide Substituted for Doxorubicin (R-CEOP): Excellent Outcome in Diffuse Large B Cell Lymphoma for Patients with a Contraindication to Anthracyclines Oral and Poster Abstracts Oral Session: Lymphoma: Chemotherapy, excluding Pre-Clinical Models - NonHodgkin Lymphoma: Therapy Monday, December 7, 2009: 11:45 AM 3. How I treat patients with diffuse large B-cell lymphoma James O. Armitage. Blood 2007; 110: 29-36 4. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy Kerry J. Savage,1 Nathalie A. Johnson,2 Susana Ben-Neriah et al Blood. 2009;114: 3533-3537) 5. Boehme V, Schmitz N, Zeynalova S, et al. CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: an analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Blood. 2009;113:3896–3902 6. Peyrade F, Jardin F, Thieblemont C, et al. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large Bcell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol 2011; 12: 460468. MCCN guidelines for treatment of diffuse large B cell lymphoma (DLBCL) January 2012 For review January 2013 Page 7 of 7