Guidelines for the Treatment of Diffuse Large B Cell Lymphoma (DLBCL)

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
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