Presentation is loading. Please wait.

Presentation is loading. Please wait.

Rituximab efficacy in other haematological malignancies Christian Buske.

Similar presentations


Presentation on theme: "Rituximab efficacy in other haematological malignancies Christian Buske."— 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 Rituximab (mg/m 2 ) Response rate (%) (n=24)*(n=7)*(n=9)*(n=39)* * Evaluable patients O’Brien et al. J Clin Oncol. 2001;19:2165.

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

5 Rituximab thrice weekly for CLL: median progression-free survival Adapted from Byrd et al. J Clin Oncol. 2001;19:2153. 2046 810 121416 1820 0 40 60 80 100 Months Patients (%) Responders All patients

6 Progression-free survival: rituximab plus fludarabine (9712) versus fludarabine arm of 9011 Rituximab + fludarabine CALGB 9712 Fludarabine CALGB 9011 Retrospective analysis 1.0 0.8 0.6 0.4 0.2 0 020406080100120140 Months Probability of progression-free survival p<0.0001 Byrd J, et al. Blood 2005;105:49–53

7 Overall survival: rituximab plus fludarabine (9712) versus fludarabine arm of 9011 Rituximab + fludarabine CALGB 9712 Fludarabine CALGB 9011 Retrospective analysis 1.0 0.8 0.6 0.4 0.2 0 020406080100120140 Months p=0.0006 Probability of progression-free survival Byrd J, et al. Blood 2005;105:49–53

8 MabThera + fludarabine/cyclophosphamide (FCR) for previously untreated CLL: protocol MabThera 375mg/m 2 (cycle 1) or 500mg/m 2 (cycles 2–6) Fludarabine 25mg/m 2 8152229 12341234 Cycle 1 Start cycle 2 8152229 123123 Cycles 2–6 Cycle repeats Cyclophosphamide 250mg/m 2 Days Keating M, et al. Blood 2005;106;599a (Abstract 2118)

9 FCR for previously untreated CLL: p atient 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 10 3 /μl (2.1–620) Platelets (range)154 x 10 3 /μl (8–406) Splenomegaly (%)51 Patient characteristics Keating M, et al. Blood 2005;106;599a (Abstract 2118)

10 FCR for previously untreated CLL: r esponse rates Response rate (%) CR72 nPR10 PR12 ● The pretreatment characteristic most strongly associated with CR rate was β 2-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 (%) CR217 83* 84* nPR 31 64 84 PR 37 38 50 Overall 300 77 (CR + PR) 83 *p<0.01 ● PCR for IgV H 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 Secondary cancers17.7 AML 1 Myelodysplastic syndrome 1 AIHA 8.3 Red cell aplasia 2 Patients (%) Keating M, et al. Blood 2005;106;599a (Abstract 2118)

13 Proportion 1.0 0.8 0.6 0.4 0.2 0.0 PatientsFailedEx 202185F ± P 9263FC 22453FCR 012243648607284 p=0.004 p<0.001 Months Time to failure by initial treatment: historical comparison of F+P vs FC vs FCR 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 1.0 0.8 0.6 0.4 0.2 0 0123456789101112 Years Proportion surviving Wierda W, et al. Blood 2003;102:110a (Abstract 373) PatientsDiedProtocolMedian (months) 251241F ± P*19 111 83FC*29 143 55FC + rituximab42+ p<0.01 p<0.04 *Historical controls

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

17 CFAR: doses and schedule Drug Dose Day of course Cyclophosphamide 250mg/m 2 3–5 Fludarabine 25mg/m 2 3–5 Alemtuzumab 30mg 1, 3, 5 Rituximab 375–500mg/m 2 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 sole5% 6q del sole 2% 13q del 5% Diploid17% +12 8% Wierda W, et al. Blood 2005;106:213a (Abstract 719)

19 Patient characteristics CFAR (cont.) Median no. prior Rx3 (1–14) Alk refractory35 (56%) Flu refractory28 (44%) Prior FC11 (17%) Front-line 3 Salvage 8 Prior FCR 32 (51%) Front-line13 Salvage19 Prior SCT 4 (6%) Wierda W, et al. Blood 2005;106:213a (Abstract 719)

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

21 Response by patient characteristics: CFAR (n=63) 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** Response (%) *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  2 M 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 Patients (%) CFAR FCR n=63 n=177 Toxicity G3 G4G3 G4 Neutropenia 17 7115 66 Thrombopenia 24 3516 18 Haematological toxicities: CFAR Wierda W, et al. Blood 2005;106:213a (Abstract 719)

24 Waldenström’s macroglobulinaemia

25 Single-agent rituximab for the treatment of WM ReferencenOR (%)PR (%)Median Dimopoulos et al. 2002 1 27-44TTP: 16 months Treon et al. 2002 2 297346TTF*: not reached *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) Lymphoplasmocytic72% Lymphoplasmocytoid28% Median age 61 years IPI int/high or high23% 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) Buske C, et al. Ann Onco 2005l;16:v110 (Abstract 250) TTF after 4 years: median not reached (R-CHOP) vs 1.8 years (CHOP); p=0.003 92* 70* 11* 5* *p=0.035

29 PTLD

30 PTLD: response rates to single-agent rituximab and R-chemo ReferenceTreatmentnPR (%)CR (%)OR (%) Choquet et al. 2002 Rituximab monotherapy 55-32.745.5 Trappe et al. 2005 Rituximab, CHOP + G-CSF 2920.862.583.3 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


Download ppt "Rituximab efficacy in other haematological malignancies Christian Buske."

Similar presentations


Ads by Google