Download presentation
Presentation is loading. Please wait.
Published byKeyon Masker Modified over 10 years ago
1
First-line management of follicular lymphoma: Will induction and maintenance treatment prolong survival? Robert Marcus Department of Haematology, Addenbrooke’s Hospital, Cambridge, UK
2
Trial 1: R-CVP versus CVP study design
Follicular NHL (IWF B, C, D) Stage III−IV 18 years No prior Rx Measurable disease Central histology review R A N D O M I S E R E S T A G R-CVP x 4 cycles (q3wk) R-CVP x 4 cycles (q3wk) CR, PR CVP x 4 cycles (q3wk) CVP x 4 cycles (q3wk) SD PD off study Rituximab 375 mg/m2 iv day 1 Cyclophosphamide 750 mg/m2 iv day 1 Vincristine 1.4 mg/m2 iv day 1 Prednisolone 40 mg/m2 po days 1–5 Marcus R, et al. Blood 2005; 105:1417–1423.
3
Participating sites Australia Belgium Brazil Canada France Israel
K Bradstock, J Catalano, R Herrmann, J McKendrick, J Norman, D Rosenfeld, K Taylor Belgium M Bron, R De Bock, F Offner Brazil C Chiattone Canada A Belch, I Bence-Bruckler, M Crump, D Forrest, K Imrie, KS Robinson, C Shustik France S Castaigne, P Solal-Céligny Israel M Shaklai Poland A Dmoszynska, K Kuliczkowski, J Walewski Portugal F Placido, J Raposo, J Veiga Spain JN Batista, M Constenla, E Flores, J Gomez Codina, J Guma, A Rueda Switzerland T Cerny, R Zenhausern UK D Cunningham, DJ Dunlop, E Fitzsimons, BW Hancock, C Hatton, P Johnson, R Marcus, G Morgan, A Pagliuca, R Pettengell, M Potter, C Poynton, S Proctor
4
Patient characteristics
R-CVP (n = 162) CVP (n = 159) Median age, years 52 53 Histology Grade 3 FL, % 9 8 Bulky disease, % 39 46 FLIPI 3−5 (poor prognosis), % 40 47 FLIPI 2 (intermediate prognosis), % 41 37 FLIPI 0−1 (good prognosis), % 19 15 Central review of pathology performed on 90% of patients FL diagnosis confirmed in 95% of patients Marcus R, et al. Blood 2005; 105:1417–1423.
5
Response rates* Response R-CVP (n = 162) CVP (n = 159) p-value
CR/CRu (%) 41 10 p < PR (%) 40 47 ORR (%) (CR+CRu+PR) 81 57 * Response up to 42 days after completion of treatment Marcus R, et al. Blood 2005; 105:1417–1423.
6
Conclusions Rituximab plus CVP improved:
Overall and complete response rates TTP, TTNLT, DFS Overall survival Addition of rituximab did not substantially increase regimen toxicity 8 cycles of R-CVP should be considered as standard treatment for previously untreated FL
7
Trial 2: R-CHOP versus CHOP study design
Patients < 60 years (< 65 years) R A N D O M I S T R A N D O M I S T PBSCT CR, PR 6–8 cycles x CHOP 6–8 cycles x CHOP plus rituximab Standard IFN-maintenance Patients > 60 years (> 65 years) Intensive IFN-maintenance Standard IFN-maintenance Hiddemann W, et al. Blood 2005; 106:3725–3732.
8
TTF is significantly improved with rituximab-based induction therapy
Patients aged > 60 years 1.0 0.8 R-CHOP (78/112) Median 5 years 0.6 Probability 0.4 CHOP (37/109) Median 2.1 years 0.2 p < 0.0 1 2 3 4 5 6 Years Buske C, et al. Blood 2006; 108:Abstract 482.
9
Patients aged > 60 years
Overall survival is significantly improved with rituximab-based induction therapy Patients aged > 60 years 1.0 R-CHOP (102/112) 0.8 CHOP (89/109) 0.6 Probability 4-year OS R-CHOP: 90% CHOP: 81% 0.4 0.2 p = 0.039 0.0 1 2 3 4 5 6 Years Buske C, et al. Blood 2006; 108:Abstract 482.
10
Survival is significantly improved with R-CHOP in all FLIPI subgroups
1.0 1.0 Median NR 0.8 0.8 Median 4.1 years Median NR 0.6 0.6 Survival probability Survival probability Median 3.0 years Median 4.0 years 0.4 0.4 0.2 0.2 Median 2.0 years 1 2 3 4 5 6 1 2 3 4 5 6 Time (years) Time (years) FLIPI 0–1: Low risk p = FLIPI 2: Intermediate prognosis p < FLIPI 3–5: Poor prognosis p = Buske C, et al. Blood 2006; 108:Abstract 482 and unpublished data.
11
Trial 3: R-MCP versus MCP study design
ESTAGING R A N D O M I S E Advanced FL, IC and MCL 18–75 years No prior rituximab Central histology review Written informed consent R-MCP 6 cycles (q4wk) R-MCP 2 cycles (q4wk) CR, PR MCP 6 cycles (q4wk) MCP 2 cycles (q4wk) IFN-maintenance for FL SD PD off study Rituximab 375mg/m2 iv d 1 Mitoxantrone 8 mg/m² iv d 3 and 4 Chlorambucil 3 x 3mg/m² po d 3–7 Prednisolone 25 mg/m² po d 3–7 Herold M, et al. J Clin Oncol 2007; April 9 (Epub).
12
Rituximab-based induction therapy significantly improves survival in patients with FL
ITT population: Median follow-up 47 months 1.00 R-MCP: Median NR 0.75 MCP: Median NR Survival distribution function 0.50 4-year OS R-MCP: 87% MCP: 74% 0.25 p = 10 20 30 40 50 60 Time (months) Herold M, et al. J Clin Oncol 2007; April 9 (Epub).
13
PFS is significantly improved with R-MCP in all FLIPI subgroups
Median NR 4-year PFS: 82% 1.0 1.0 Median 36 months 4-year PFS: 43% 0.8 0.8 Median NR 4-year PFS: 61% 0.6 0.6 Survival probability Survival probability 0.4 0.4 Median 26.5 months 4-year PFS: 36% 0.2 0.2 10 20 30 40 50 60 10 20 30 40 50 60 Time (months) Time (months) FLIPI 2: Intermediate prognosis p = FLIPI 3–5: Poor prognosis p = Herold M, et al. J Clin Oncol 2007; April 9 (Epub) and unpublished data.
14
Trial 4: R-CHVP-IFN vs CHVP-IFN study design
Arm A 6 months 12 months R Staging including CT-scan and bone marrow biopsy Arm B d1 Cyclophosphamide 600 mg/m2 d1 Doxorubicin 25 mg/m2 d1 Etoposide 100 mg/m2 d1–5 Prednisolone 40 mg/m2 αIFN 2b, 4.5 MU tiw for 18 months (3 MU if aged 70 yr) Rituximab: 375 mg/m2 every month for 6 months (arm A & B) then every 2 months in arm A Foussard C, et al. J Clin Oncol 2006; 24(18S):Abstract 7508.
15
EFS and OS are significantly increased with rituximab-based therapy
100 100 R-CHVP + IFN- (Arm B) R-CHVP + IFN- (Arm B) 91% Event-free survival 75 Ovarall survival 75 CHVP + IFN- (Arm A) 84% 67% 50 50 46% CHVP + IFN- (Arm A) 25 25 p < p = 0.029 10 20 30 40 50 60 70 10 20 30 40 50 60 70 Months Months Foussard C, et al. J Clin Oncol 2006; 24(18S):Abstract 7508.
16
First-line rituximab-based induction therapy improves overall survival
Induction regimen Outcome (median) Overall survival CHVP R + IFN-1 EFS NR vs 3 yrs p < 3.5 yr 91% vs 84% p = 0.029 MCP R2 PFS NR vs 29 mo p < 4 yr 87% vs 74% p = CHOP R3 TTF NR vs 31 mo p = 2 yr 95% vs 90% p = 0.016 CVP R4 TTP 34 mo vs 15 mo p < 83% vs 77% p = 1. Foussard C, et al. J Clin Oncol 2006; 24:Abstract 7508. 2. Herold M, et al. J Clin Oncol 2007; April 9 (Epub). 3. Hiddemann W, et al. Blood 2005; 106:3725– Marcus R, et al. Blood 2006; 108:Abstract 481.
17
Rituximab-based induction therapy: Conclusions
R-Chemo yields superior results to chemotherapy in four prospective randomised trials The FLIPI predicts outcome in all studies Prognosis was worse with a high FLIPI score Majority of patients with poor prognosis will relapse within 4–5 years There does not seem to be a TTP/PFS ‘plateau’ of any subgroup in any trial yet
18
Overall survival improvement with rituximab in FL
1.0 GLSG study NHL 2000 0.8 0.6 GLSG study NHL 1996 Survival probability 0.4 0.2 p < 0.0 12 24 36 48 60 72 84 96 108 120 Time (months) Number of patients at risk: NHL 1996 538 485 457 419 386 332 242 125 46 NHL 2000 794 621 440 250 108 8 Hiddemann W, et al. Blood 2006; 108:Abstract 483.
19
Phase III trial of CVP ± rituximab maintenance
Rituximab maintenance after CVP in untreated indolent NHL: ECOG 1496 study design Phase III trial of CVP ± rituximab maintenance 401 patients with previously untreated indolent NHL, 322 randomised R A N D O M I S E Rituximab maintenance 375 mg/m2 q1wk 4 q6mo 4 CVP 6–8 cycles PR, CR or SD Observation
20
Rituximab maintenance therapy significantly prolongs PFS in FL
Median PFS from randomisation: 15 mo vs 61 mo 1.0 0.8 Rituximab maintenance (n = 120) 0.6 Probability 0.4 0.2 Observation (n = 117) p = 0.0 1 2 3 4 5 6 Years from maintenance randomisation Hochster H, et al. Blood 2005; 106:Abstract 349.
21
Median PFS/EFS (months)
Rituximab monotherapy induction and maintenance in first-line treatment of FL Patients (n) Median FU (months) Induction regimen Maintenance schedule Median PFS/EFS (months) Minnie Pearl Phase II1 38† 55 R-Mono* q6mo x 4* PFS: 52 SAKK 35/982 64 36 q2mo x 4 EFS: 19 vs 36 p = 0.009 * 375 mg/m2 rituximab once weekly x 4 † Follicular lymphoma patients only FU = follow-up 1. Hainsworth JD, et al. Blood 2003; 102:Abstract 1496. 2. Ghielmini M, et al. Blood 2004; 103:4416–4423.
22
SAKK 35/03 study: Efficacy of extended rituximab maintenance therapy in FL
Short maintenance Rituximab maintenance q2mo x 4 R Rituximab375 mg/m² weekly x 4 PR, CR Rituximab maintenance q2mo until relapse (maximum 5 years) PD, SD off study Long maintenance
23
Rituximab maintenance therapy
PRIMA study: Efficacy of rituximab-based induction and maintenance in first-line indolent NHL Rituximab maintenance therapy 1 x q8wk for 24 months R A N D O M I SE 8 x rituximab + 8 x CVP or 6 x CHOP or 6 x FCM Indolent NHL stages III–IV, untreated CR, PR Observation SD PD off study
24
RiCHOP trial: Efficacy of ASCT followed by rituximab maintenance in indolent NHL
HDT ASCT R A N D O M I SE Rituximab maintenance 1 x q8wk for 24 months CR, PR R-CHOP x 6 + R x 2 SD PD off study N > 600 patients with indolent FL (< 65 years old). Study start 2007
25
A note of caution! Incidence of hepatitis B reactivation with rituximab
Out of 456 patients, 32 were Hep B positive 14 received rituximab monotherapy 18 received rituximab plus chemotherapy Group Patients (n) HBsAg HBsAb HBcAb Liver event (%) A 12 – + 3 (25) B 6 2 (33) C 8 Not available 2 (25) D Variable 4 (66) A total of 5 patients developed liver failure (15%) Hanbali A, et al. Blood 2006; 108:Abstract 2766.
26
But…prophylactic lamivudine can reduce the incidence of hepatitis during chemotherapy
Non-randomised comparison of lymphoma patients treated with prophylactic lamivudine during chemotherapy with historical controls 100 mg was administered daily for up to 64 weeks % Control (n = 116) % Lamivudine (n = 40) p-value Hepatitis incidence during chemo 52 18 0.000 Disruption in chemo administration 37 10 0.001 Lamivudine prophylaxis reduced the incidence of hepatitis Li Y, et al. Cancer 2006; 106:1320–1325.
27
Outstanding questions in first-line therapy for FL
Do more intensive therapies yield superior results than R-CVP? If so do ALL patients require such therapy, or only poor prognosis patients? Which component provides superior results? Anthracycline, interferon or both? Does maintenance have a role in first-line FL? PRIMA trial to provide evidence Do PBSCT or other approaches have a role in first-line therapy?
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.