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What is the Optimal Approach to CLL, BR vs. FCR/FR? Michael J. Keating MD Anderson Cancer Center Presented by: Richard R. Furman Weill Cornell Medical.

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Presentation on theme: "What is the Optimal Approach to CLL, BR vs. FCR/FR? Michael J. Keating MD Anderson Cancer Center Presented by: Richard R. Furman Weill Cornell Medical."— Presentation transcript:

1 What is the Optimal Approach to CLL, BR vs. FCR/FR? Michael J. Keating MD Anderson Cancer Center Presented by: Richard R. Furman Weill Cornell Medical College

2 Bendamustine Bifunctional Antineoplastic Agent Rummel M, J Clin Oncol. 2005;23:3383. ClH 2 C N N N CH 3 CO 2 H Purine-like Benzimidazole Ring Alkylating Group ClH 2 C Available in Germany, Unique in vitro anti-tumor profile

3 Proportion Fludarabine + Prednisone (1983 – 1993) Progression Free Survival Median PFS: 26 months

4 Long Term Outcomes for FR: CALGB 9712 Months Survival

5 Chlorambucil vs. Bendamustine in Untreated CLL: Progression-Free Survival Knauf WU. JCO. 2009; 27:4378

6 GCLLSG CLL2M: BR in Untreated CLL Treatment: Bendamustine 90 mg/m2 days 1,2 (cycles 1-6) Rituximab: 375 mg/m2 (cycle 1) 500 mg/m2 (cycles 2-6) Study Characteristics: 117 patients No age limit (median=64; range 34-78) 73.5% received all 6 cycles Fischer K. JCO 2012; 30:3209.

7 CLL2M: BR in Untreated CLL: Event Free Survival median EFS = 33.9 months

8 CLL2M: BR in Untreated CLL: Response Rates ResponseN=124% ORR CR nPR PR SD PD - - Fischer K. JCO 2012; 30:3209.

9 BR: Adverse Events, Grades 3+4 (pts) Adverse EventGrade 3 (%)Grade 4 (%) Hematologic Toxicities: Leucopenia Neutropenia Thrombocytopenia Anemia Tumor lysis syndrome2.60 Allergic reaction Infectious Other non-hematologic

10 Phase III Trial of FC + / - Rituximab in Untreated CLL: GCLLSG CLL8 Trial Untreated No age restriction Active CLL requiring therapy Primary endpoint: PFS No age limit 74% of patients received all 6 courses of FCR Fludarabine 25 mg/m 2, d1-3 Cyclophosphamide 250 mg/m 2, d1-3 (n = 817) RANDOMIZERANDOMIZE Fludarabine 25 mg/m 2, d1-3 Cyclophosphamide 250 mg/m 2, d1-3 Rituximab 500 mg/m 2, d1 (375 mg/m 2 initial dose) x 6 cycles FOLLOWUPFOLLOWUP Hallek M. Lancet 2010; 376:1164

11 FCR vs. FC in Untreated CLL: GCLLSG CLL8 Trial FCRFCp PFS51.8 m32.8 m<.001 ORR95.1%88.4%.001 CR44.1%21.8%<.001 PR51%66.6%<.01 OS (3yr)87%83%.01 Hallek M. Lancet 2010; 376:1164

12 GCLLSG CLL8: FCR vs. FC Progression Free Survival Cumulative Survival Fischer K. ASH Median PFS: FCR 57 months FC 33 months Median follow-up: 5.9 years

13 CLL8: Adverse Events (pts) Hallek M. Lancet 2010; 376:1164

14 Response Comparison ResponseBR (%)FCR (%) ORR CR PR Median PFS33.9 mo57.0 mo

15 AE Comparison Adverse EventBR (%)FCR (%) Hematologic Toxicity Neutropenia Thrombocytopenia Anemia Infections7.746 Tumor Lysis Syndrome2.61

16 Patient Comparison CharacteristicBR (%)FCR (%) Age > Binet Stage C IgVH unmutated Del 11q / 17p Zap

17 Patient Comparison CharacteristicBR (%)FCR (%) Age > Binet Stage C IgVH unmutated Del 11q / 17p Zap

18 FCR300: First-line Outcomes Department of Leukemia UT MD Anderson Cancer Center Houston, TX

19 Response to FCR (NCI-WG: 300 Patients) Response# of Pts(%) ORR28595 CR21772 nPR3110 PR3712 No response134 Early death21

20 FCR300: PFS and OS Months Proportion Surviving P<.0001 PFS OS

21 FCR300: PFS by IGHV Mutation Status Months Proportion Progression-free IGHV-M IGHV-UM Group Events Total P<.0001 Unknown 39 87

22 FCR vs. BR: The Tally FCRBR Duration of follow up ORR CR PFS Toxicity Profile

23 CLL10 GCLLSG: Randomized Trial of FCR vs. BR ASH 2013? fludarabine 25 mg/m 2 d1-3 cyclophosphamide 250 mg/m 2 d1-3 rituximab 375 mg/m 2 C1, d1 500 mg/m 2 C2-6, d1 Untreated CLL (N = 564) Randomize bendamustine 90 mg/m 2 d1,2 rituximab 375 mg/m2 C1, d1 500 mg/m2 C2-6, d1 Primary Endpoint: 2 yr


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