Zachary H. Word and Craig Moskowitz
Definition
• A heterogeneous group of neoplasms arising from mature B-cells & characterized pathologically by large atypical lymphocytes w/a diffuse growth pattern
Epidemiology
• Most common lymphoma type: ∼30% of lymphomas, ∼24K cases/y
• ↑ Incidence w/age, ↑ incidence in Caucasians, slight male predominance
Clinicopathologic Subtypes
Genetics & Molecular Subtypes
• 2 main phenotypes identified by gene expression profiling: GCB-like & ABC-like (NEJM 2008;359:2313)
• ABC phenotype a/w older age, worse prognosis
• Immunohistochemical algorithms to distinguish phenotype have been developed but reliability is unclear; not routinely used to guide management
• Translocations of the MYC gene (classically a/w Burkitt lymphoma) & various partners can be seen in DLBCL & confer ↓ prognosis
• “Double hit” lymphomas, w/FISH detected translocations of both MYC & BCL-2 have poor prognosis. IHC detected double hit lymphomas have a less severely ↓ prognosis (J Clin Oncol 2012;30:3460)
• The t(14:18) w/c is very common in Follicular Lymphoma, juxtaposes the BCL-2 gene to the IgH gene & occurs in ∼30% of DLBCLs. BCL-2 + IHC may be seen w/or w/o this translocation
Staging
• Ann Arbor Staging w/Cotswolds modifications, as for HL
Prognostic Model
• IPI includes 5 adverse RFs: Age >60, ECOG PS ≥2, ↑ LDH, >1 extranodal site & stages III–IV (NEJM 1993;329:987)
Outcomes w/rituximab containing regimens (J Clin Oncol 2010;28:2373)
Management
• DLBCL is curable w/chemotherapy, even in adv stage
• Standard of care for adv stage disease is rituximab w/CHOP (cyclophosphamide, doxorubicin, vincristine & prednisone) for 6–8 cycles
• LV function is screened w/MUGA or ECHO before doxorubicin due to risk of cardiotoxicity
• Doxorubicin can be substituted for liposomal doxorubicin or etoposide in pts w/abnl LV function. Efficacy may not be equivalent
• Cardiac tox lower w/the infusional regimen dose-adjusted EPOCH
• Interim restaging after 2–4 cycles. Change Rx if<pr< p=""></pr<>
• RT improves local control, particularly for bulky disease. ISRT has replaced traditional IFRT as the current standard (NCCN Guidelines V 1.2013, pg NHODG-D)
• Intrathecal or high-dose MTX Ppx if ↑ risk of CNS relapse
• Restage w/PET after completion of Rx
Management: Limited Stage Disease
• ∼1/3 of DLBCL pts have stages I–II disease that can be contained w/in a single radiation field
• CMT w/abbreviated R-CHOP (3 cycles) & IFRT results in 4-y PFS of 88% & OS of 92% (J Clin Oncol 2008;26:2258). ISRT is now used in place of IFRT
• 6–8 cycles of R-CHOP w/o RT (as for advances stage disease) is an option
• Imaging adapted strategies have shown promising early results, but published data are limited
Management: Primary DLBCL of the CNS
• OS ∼1.5 mos w/o Rx
• May be a/w HIV, where it is an AIDS defining CA
• R-CHOP crosses BBB poorly; should not be used for CNS disease
• For details of tx, see 1° CNS Lymphoma section
Management: Primary Testicular DLBCL
• High relapse rate w/abbreviated chemotherapy; pts should receive 6 cycles of R-CHOP even in early stage
• Local Rx (surgery or RT) to bilateral testes
• CNS Ppx
Management: Grey Zone Lymphomas
• Tx not well defined for either condition
• R-CHOP & IFRT as for 1° mediastinal DLBCL has been used in DLBCL/HL
• DLBCL/Burkitt lymphoma has high proportion of double hit biology; poor prognosis. Intensive regimens such as dose adjusted EPOCH or CODOX-M/IVAC may be favored over R-CHOP, though comparative data not available
Management: Post CR therapy
• Observation alone is currently recommended. No other postremission strategy has proven benefit
• Maintenance rituximab improves outcomes only in pts not receiving rituximab as part of induction
• ASCT has not been shown to ↑ OS, & involves significant morbidity
Relapsed/Refractory Disease: Transplant Eligible
• Therapeutic intent remains curative
• Pts w/chemosensitive disease as demonstrated by response to 2nd-line chemotherapy such as R-ICE or R-DHAP are consolidated w/ASCT
• Achievement of CR before ASCT is optimal. Consider pretransplant ISRT to sites of bulky relapse or questionable response to salvage chemotherapy
• GEM-based regimens may be effective in pts w/suboptimal response to R-ICE or R-DHAP
• RFs for adverse outcome in the relapsed/refractory setting: CR duration <12 mos, prior receipt of rituximab, IPI >1 (J Clin Oncol 2010;28:4184)
Relapsed/Refractory Disease: Transplant Ineligible
• No curative option available; Rx given w/palliative intent
• Choice of regimen depends on prior tx & response
• Pts refractory to ≥2 prior lines of cytotoxic chemotherapy are unlikely to respond to additional lines
• Palliative RT useful for symptomatic lesions