1 / 32

Rituximab efficacy in other haematological malignancies

Rituximab efficacy in other haematological malignancies. Christian Buske. CLL. Dose escalation of rituximab for CLL: response in patients with CLL. Response rate (%). (n=39)*. (n=24)*. (n=7)*. (n=9)*. Rituximab (mg /m 2 ). * Evaluable patients.

gay
Download Presentation

Rituximab efficacy in other haematological malignancies

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Rituximab efficacy in other haematological malignancies Christian Buske

  2. CLL

  3. Dose escalation of rituximab for CLL: response in patients with CLL Response rate (%) (n=39)* (n=24)* (n=7)* (n=9)* Rituximab(mg/m2) * Evaluable patients O’Brien et al. J Clin Oncol. 2001;19:2165.

  4. Thrice weekly rituximab:overall response and outcome Evaluable patients(n=33) Complete response Partial response Overall response rate Response (%) 3 42 45 • Median response duration – 10 months • Fludarabine refractory patients – 6 months Byrd J, et al. J Clin Oncol 2001;19:2153–64

  5. Rituximab thrice weekly for CLL: median progression-free survival 100 Responders All patients 80 60 Patients (%) 40 20 0 0 2 4 6 8 10 12 14 16 18 20 Months Adapted from Byrd et al. J Clin Oncol. 2001;19:2153.

  6. Progression-free survival: rituximab plus fludarabine (9712) versus fludarabine arm of 9011 Retrospective analysis 1.0 0.8 0.6 0.4 0.2 0 Rituximab + fludarabine CALGB 9712 Probability of progression-freesurvival Fludarabine CALGB 9011 p<0.0001 0 20 40 60 80 100 120 140 Months Byrd J, et al. Blood 2005;105:49–53

  7. Overall survival: rituximab plus fludarabine (9712) versus fludarabine arm of 9011 Retrospective analysis 1.0 0.8 0.6 0.4 0.2 0 Rituximab + fludarabine CALGB 9712 Probability of progression-freesurvival Fludarabine CALGB 9011 p=0.0006 0 20 40 60 80 100 120 140 Months Byrd J, et al. Blood 2005;105:49–53

  8. Start cycle 2 Cycle 1 1 2 3 4 8 15 22 29 Days Cyclophosphamide 250mg/m2 Cycle repeats Cycles 2–6 1 2 3 8 15 22 29 Days MabThera + fludarabine/cyclophosphamide (FCR) for previously untreated CLL: protocol MabThera 375mg/m2 (cycle 1) or 500mg/m2(cycles 2–6) Fludarabine 25mg/m2 Keating M, et al. Blood 2005;106;599a (Abstract 2118)

  9. FCR for previously untreated CLL: patient characteristics Patient characteristics Male (%) 70.3 Rai stage III-IV (%) 33 Median age (range) 57 (17–86) Hemoglobin (range) 12.5G% (6.1–18.7) White cell count (range) 76 x 103/μl (2.1–620) Platelets (range) 154 x 103/μl (8–406) Splenomegaly (%) 51 Keating M, et al. Blood 2005;106;599a (Abstract 2118)

  10. FCR for previously untreated CLL: response rates Response rate (%) CR 72 nPR 10 PR 12 • The pretreatment characteristic most strongly associated with CR rate was β2-microglobulin level Keating M, et al. Blood 2005;106;599a (Abstract 2118)

  11. FCR for previously untreated CLL: 4-year analysis of previously untreated CLL patients Response Patients (n) Response duration (%) Overall survival (%) CR 217 83* 84* nPR 31 64 84 PR 37 38 50 Overall 300 77 (CR + PR) 83 *p<0.01 • PCR for IgVH and flow responses were independently associated with duration of response Keating M, et al. Blood 2005;106;599a (Abstract 2118)

  12. FCR for previously untreated CLL: toxicity Patients (%) Secondary cancers 17.7 AML 1 Myelodysplastic syndrome 1 AIHA 8.3 Red cell aplasia 2 Keating M, et al. Blood 2005;106;599a (Abstract 2118)

  13. Time to failure by initial treatment:historical comparison of F+P vs FC vs FCR 1.0 0.8 0.6 0.4 0.2 0.0 Proportion Patients Failed Ex 202 185 F ± P 92 63 FC 224 53 FCR p=0.004 p<0.001 0 12 24 36 48 60 72 84 Months Keating M, et al. Proc Am Soc Clin Onc 2004

  14. FCR for previously treated CLL: response by prior therapy Patients (%) Fludarabine Fludarabine sensitive resistant (n=108) (n=37) OR 76 59 CR 31 5 PR 28 43 Nodular PR 17 11 Wierda et al., J Clin Oncol 2005;23:4070–8

  15. Relapsed/refractory CLL: overall survival by treatment regimen Patients Died Protocol Median (months) 251 241 F ± P* 19 111 83 FC* 29 143 55 FC + rituximab 42+ 1.0 0.8 0.6 0.4 0.2 0 p<0.01 p<0.04 Proportion surviving 0 1 2 3 4 5 6 7 8 9 10 11 12 Years *Historical controls Wierda W, et al. Blood 2003;102:110a (Abstract 373)

  16. Pentostatin cyclophosphamide in previously treated CLL patients: response rates 77 74 17 8 Weiss M, et al. J Clin Oncol 2003;21:1278–84

  17. CFAR: doses and schedule Drug Dose Day of course Cyclophosphamide 250mg/m2 3–5 Fludarabine 25mg/m2 3–5 Alemtuzumab 30mg 1, 3, 5 Rituximab 375–500mg/m2 2 (Allopurinol; TMP/SMX; Valacyclovir) Wierda W, et al. Blood 2005;106:213a (Abstract 719)

  18. Patient characteristics: CFAR (n=63) Rai stage (int., high risk) 30, 33 Karyotype (n=53) complex (17p=15; 11q=10) 48% 11q del sole 5% 6q del sole 2% 13q del 5% Diploid 17% +12 8% Wierda W, et al. Blood 2005;106:213a (Abstract 719)

  19. Patient characteristics CFAR (cont.) Median no. prior Rx 3 (1–14) Alk refractory 35 (56%) Flu refractory 28 (44%) Prior FC 11 (17%) Front-line 3 Salvage 8 Prior FCR 32 (51%) Front-line 13 Salvage 19 Prior SCT 4 (6%) Wierda W, et al. Blood 2005;106:213a (Abstract 719)

  20. Response Patients (%) ORR 42 (67) CR 14 (22) nPR 1 (2) PR* 27 (43) NR 17 (27) Early death 3 (5) Not evaluable 1 (2) Response assessment (NCI-WG): CFAR (n=63) *10 PRs due to persistent cytopenia Wierda W, et al. Blood 2005;106:213a (Abstract 719)

  21. Response by patient characteristics:CFAR (n=63) Response (%) Characteristic CR OR Rai Stage I–II (n=30) 27 80 III–IV (n=33) 18 52* Fludarabine sensitive (n=35) 37** 83 Fludarabine resistant (n=28) 4** 46** *p<0.02 **p<0.01 Wierda W, et al. Blood 2005;106:213a (Abstract 719)

  22. Multivariate analysis: FCR and CFAR (n=231) Variable CR TTP OS Flu-Ref <0.001 2M 0.003 <0.001 No. prior Rx <0.001 ALB 0.03 Rai stage <0.001 Cytogenetics <0.01 PLT 0.03 Protocol 0.90 0.27 0.07 p-value Wierda W, et al. Blood 2005;106:213a (Abstract 719)

  23. Haematological toxicities: CFAR Patients (%) CFAR FCR n=63 n=177 Toxicity G3 G4 G3 G4 Neutropenia 17 71 15 66 Thrombopenia 24 35 16 18 Wierda W, et al. Blood 2005;106:213a (Abstract 719)

  24. Waldenström’s macroglobulinaemia

  25. Single-agent rituximab for the treatment of WM *Median follow-up of 20 months 1. Dimopoulos M, et al. J Clin Oncol 2002;20:2327–33 2. Treon S, et al. Blood 2002;100:813a (Abstract 3211)

  26. Rituximab plus chemotherapy for the treatment of WM • Dimopoulos et al. 2004 • previously untreated WM patients (n=34) • treated with dexamethasone, rituximab and cyclophosphamide • mean follow-up of 18 months 90% of pts progression free • Treon et al. 2002 • previously treated WM patients (n=23) • treated with rituximab plus fludarabine • 85.7% of evaluable patients responded Dimopoulos M, et al. Blood 2004;104:215a (Abstract 752) Treon S, et al. Blood 2002;100;211a (Abstract 794)

  27. R-CHOP vs CHOP in previously untreated LP-IC: patients • Patients (n=75) with previously untreated lymphoplasmocytoid/ic immunocytoma (LP-IC) • Lymphoplasmocytic 72% Lymphoplasmocytoid 28% Median age 61 years IPI int/high or high 23% Buske C, et al. Ann Onco 2005l;16:v110 (Abstract 250)

  28. R-CHOP vs CHOP: response in patients with lymphoplasmocytoid/ic immunocytoma (LP-IC) 92* 70* 11* 5* *p=0.035 TTF after 4 years: median not reached (R-CHOP) vs 1.8 years (CHOP); p=0.003 Buske C, et al. Ann Onco 2005l;16:v110 (Abstract 250)

  29. PTLD

  30. PTLD: response rates to single-agent rituximab and R-chemo Choquet S, et al. Blood 2003;102:277a (Abstract 986) Trappe R, et al. Blood 2005;106:274a (Abstract 932)

  31. Front-line rituximab improves overall and event-free survival in patients with PTLD • 108 patients with PTLD enrolled in the study • 33% treated with rituximab • In the whole group • CR: 46% • PR: 13% • Patients treated with rituximab had significantly prolonged OS and EFS compared to the group as a whole (median follow-up of 15.2 months) • OS: 76% vs 21% (p=0.007) • EFS: 70% vs 15% (p=0.02) Gonzalez-Barca E, et al. Blood 2004;104:394a (Abstract 1406)

  32. Rituximab efficacy in other haematological malignancies: conclusions • Rituximab in combination with fludarabine and cyclophosphamide is one of the most active regimens for the treatment of CLL • now being evaluated in phase III trials • Promising response rates in fludarabine refractory CLL patients have been achieved with rituximab containing regimens • Single-agent rituximab and rituximab/chemotherapy combinations have also demonstrated efficacy in LP-IC, WM and PTLD and warrant further investigation

More Related