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Extending survival in relapsed indolent lymphoma with induction and maintenance

Extending survival in relapsed indolent lymphoma with induction and maintenance. Rien van Oers Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. Maintenance in indolent lymphoma: Rationale. Prolonged remission predicts for improved overall survival 1 –3

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Extending survival in relapsed indolent lymphoma with induction and maintenance

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  1. Extending survival in relapsed indolent lymphoma with induction and maintenance Rien van OersAcademic Medical Center, University of Amsterdam, Amsterdam, Netherlands

  2. Maintenance in indolent lymphoma: Rationale • Prolonged remission predicts for improved overall survival1–3 • Delays the need for next treatment (QoL) • Improves response quality over time (PR  CR) • Eradicates minimal residual disease, thereby potentially increasing overall survival 1. Gallagher C, et al. J Clin Oncol 1986; 4:14701480. 2. Weisdorf D, et al.J Clin Oncol 1992; 10:942947. 3. Montoto S, et al. Ann Oncol 2002; 13:523530.

  3. The EORTC 20981 trial CHOP or R-CHOP followed by rituximab maintenance therapy or observation

  4. Study design R A N D O M I S E R A N D O M I S E R-CHOP q21dmaximum 6 cycles Rituximab maintenance therapy* CRPR n = 234 n = 167 CHOP q21dmaximum 6 cycles Observation n = 167 n = 231 * 375 mg/m2 every 3 months for 2 years or until relapse van Oers M, et al. Blood 2006; 108:3296–3301.

  5. Patient characteristics van Oers M, et al. Blood 2006; 108:3296–3301.

  6. Rituximab-based induction chemotherapy improves response rates * p < 0.0001 van Oers M, et al. Blood 2006; 108:3296–3301.

  7. Rituximab-based induction chemotherapy significantly improves PFS 100 90 80 70 60 Patients (%) 50 R-CHOP median: 33.1 months 40 CHOP median: 20.2 months 30 20 10 p < 0.001 0 0 1 2 3 4 5 6 Years van Oers M, et al. Blood 2006; 108:3296–3301.

  8. Rituximab maintenance prolongs PFS by more than 3 years PFS after R-CHOP/CHOP induction in EORTC 20981 trial 100 90 PFS > 3 years 80 70 Rituximab maintenance median: 51.5 months 60 Patients (%) 50 40 30 Observation median: 14.9 months 20 10 p < 0.001 0 0 1 2 3 4 5 Years van Oers M, et al. Blood 2006; 108:3296–3301.

  9. Rituximab maintenance improves PFS irrespective of induction regimen PFS after CHOP induction PFS after R-CHOP induction 100 100 80 80 MaintenanceMedian: 51.8 months Maintenancemedian: 42.2 months 60 60 40 40 Observationmedian: 11.6 months ObservationMedian: 23.0 months 20 20 p < 0.001 p = 0.004 0 0 5 0 1 2 3 4 5 0 1 2 3 4 Years Years van Oers M, et al. Blood 2006; 108:3296–3301.

  10. Rituximab maintenance improves PFS irrespective of induction response PFS after CR PFS after PR 100 100 Maintenancemedian: 51.6 months 80 80 Maintenancemedian: 45.4 months 60 60 Observationmedian: 14.5 months 40 40 Observationmedian: 15.6 months 20 20 p = 0.0009 p < 0.0001 0 0 5 0 1 2 3 4 5 0 1 2 3 4 Years Years van Oers M, et al. Blood 2006; 108:3296–3301.

  11. Rituximab maintenance significantly improves overall survival OS after CHOP/R-CHOP induction in EORTC 20981 trial 100 Rituximab maintenance: 3 years 85.1% 90 80 70 60 Patients (%) 50 40 Observation: 3 years 77.1% 30 20 p = 0.011 HR: 0.52 10 0 0 1 2 3 4 6 5 Years van Oers M, et al. Blood 2006; 108:3296–3301.

  12. Benefits of a 3-year prolonged remission • Improved quality of life • Less disease-related symptoms • Fewer therapies administered over time • Less hospital time • Less time dealing with therapy-associated side-effects • Prolonged remission associated with significant improvement in overall survival

  13. The GLSG trial FCM or R-FCM followed by rituximab maintenance therapy or observation

  14. Rituximabplus4 x FCM 4 x FCM Study design Rituximab maintenance therapy* R A N D O M I S E R A N D O M I S E CR/PR Advanced stage relapsed/refractory FL or MCL Observation only CR/PR * 4 x rituximab (375 mg/m2) at 3 and 9 months after induction Forstpointner R, et al. Blood 2004; 104:3064–3071.

  15. 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 Rituximab-based induction therapy improves survival in relapsed/refractory FL Randomised to R-FCM (29/37) Added to R-FCM arm (55/65) Probability Randomised to FCM (17/31) p = 0.0310; p = 0.0290 Time (years after start of therapy) Forstpointner R, et al. Blood 2004; 104:3064–3071 and update.

  16. Rituximab maintenance after rituximab-based induction significantly prolongs remission in FL 1.0 Response duration after R-FCM induction 0.9 0.8 Maintenance (32/41) 0.7 0.6 Probability 0.5 0.4 0.3 Observation (21/40) 0.2 0.1 p = 0.035 0.0 0 1 2 3 4 5 6 7 Time (years after start of therapy) Forstpointner R, et al. Blood 2006; 108:4003–4008.

  17. Rituximab maintenance after rituximab-based induction extends survival 1.0 OS after R-FCM induction 0.9 0.8 Maintenance (56/67) 0.7 0.6 Probability 0.5 Observation (49/71) 0.4 0.3 0.2 0.1 p = 0.0562 0.0 0 1 2 3 4 5 6 7 Time (years after end of induction) Forstpointner R, et al. Blood 2006; 108:4003–4008.

  18. Rituximab maintenance therapy Toxicity profile of rituximab allows prolonged treatment beyond induction

  19. EORTC trial: Rituximab maintenance therapy is well tolerated No treatment-related deaths were observed with rituximab maintenance therapy van Oers M, et al. Blood 2006; 108:3296–3301.

  20. GLSG trial: No significant increase in grade 3/4 events with rituximab maintenance Forstpointner R, et al. Blood 2006; 108:4003–4008.

  21. Rituximab-based induction and maintenance is the standard of care for relapsed FL • Rituximab-based induction therapy improves response rates • Maximises the number of patients able to benefit from rituximab maintenance • Rituximab maintenance improves PFS by more than 3 years • Extended remission improves patient QoL • Rituximab maintenance improves overall survival

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