Follicular & Aggressive B-Cell Lymphomas

Five-year TTF and Response Duration (RD) According to FLIPI Risk Group R-CHOPCHOPP value TTF Low-risk Median not reached vs. 3.9 years Intermediate-risk Median not reached vs. 3.4 years High-risk Median 5 years vs. 2.3 years RD Low-risk Median not reached vs. 3.8 years Intermediate-risk Median not reached vs. 3.4 years High-risk Median 5 years vs. 2.3 years Adapted from Hoster et al. 10-ICML 2008, abstract 330.

Most common single type of lymphoma in North America Median age at presentation: 65 years 90% harbour advanced-stage disease requiring systemic intervention 40% asymptomatic patients  no initial intervention needed >80% of asymptomatic patients require treatment within 4–5 years Median survival – >7–8 years overall – >12–15 years in patients <65 years old 10% to 20% die in the first 2 years Most patients die due to lymphoma Transformation to DLBCL 3% per year and often proves rapidly fatal Characteristics Still True of Follicular Lymphoma in 2008 Adapted from Connors JM. 10-ICML 2008.

Results with Addition of Rituximab Addition to primary chemotherapy improves –Progression-free survival (PFS) –Overall survival (OS) Addition to second-line chemotherapy improves –PFS and OS Maintenance therapy with rituximab improves –PFS and OS Definite after second-line immunochemotherapy Probable after primary immunochemotherapy It can be given safely by rapid infusion, sparing treatment resources It substantially improves outcomes for transformed lymphoma Adapted from Connors JM. 10-ICML 2008.

Follicular Lymphoma: BC Cancer Agency Approach Limited stage –Involved field radiation 50% eventually progress Advanced stage, asymptomatic –Observation 90% eventually progress Advanced stage, symptomatic –R-CVP x 8 cycles –Maintenance rituximab 375 mg/m 2 q 3 months x 8 doses (2 years) –All doses of rituximab after first dose given by rapid infusion (90 min)  20% over 30 min (50 or 100 mL)  80% over 60 min (200 or 400 mL) Adapted from Connors JM. 10-ICML 2008.

Previously untreated patients with symptomatic FL R-CVP x 8 cycles >90% with responsive disease also receive maintenance rituximab 375 mg/m 2 q 3 months for 2 years Transformed disease: add doxorubicin (R-CHOP) + rituximab maintenance Benefits: Reserves doxorubicin until crucially necessary Maximizes impact of immunotherapy with rituximab Minimizes overall impact on resources Rapid rituximab infusion convenient for outpatient treatment: (maintenance with 8 cycles) Follicular Lymphoma: BC Cancer Agency Approach Adapted from Connors JM. 10-ICML 2008.

European MCL Network: Results of Combined Immunochemotherapy at 12 Months Adapted from Dreyling et al. 10-ICML 2008, abstract 300. n=269n=286

Dose Treatment Days Infusional Agents  Etoposide 50 mg/m 2 /day  Vincristine 0.4 mg/m 2 /dayDays 1 to 4  Doxorubicin 10 mg/m 2 /day Cycle: 21 days Bolus Agents  Cyclophosphamide 750 mg/m 2 /dayDay 5 All patients receive IT MTX  Prednisone 60 mg/m 2 /day b.i.d. Days 1 to 5 Biological Agents  G-CSF 5 mg/kgDays 6 to 15  Rituximab 375 mg/m 2 /dayDay 1 Pharmacodynamic dosing based on neutrophil nadir DA-EPOCH-R Regimen Adapted from Dunleavy et al. 10-ICML 2008, abstract 009.

Median follow-up: 28 months Responses (n=24):Toxicity: CR/CRu100%One case of tumour OS100%lysis syndrome EFS 96%FN in 16% of cycles DA-EPOCH-R: Results and Conclusions in Patients with Untreated Burkitt’s Lymphoma (BL) Conclusions: Highly effective in BL Low toxicity in all patient groups Future study planned in BL with risk-adaptive design Adapted from Dunleavy et al. 10-ICML 2008, abstract 009.