Daryl Tan Raffles Cancer Center Visiting Consultant Singapore
- Slides: 88
�泡淋巴瘤治�策略更新 Daryl Tan Raffles Cancer Center Visiting Consultant Singapore General Hospital Adjunct Assistant Professor, Duke-NUS Graduate Medical School MJR
FL治�中的�察与等待 MJR Horning S, SA Rosenberg. NEJM 1984; 311: 1471 -76
�后良好患者�察等待�和治 ��的无治�失�率 Solal-Ce´ligny, et al. Watchful Waiting in Low–Tumor Burden Follicular Lymphoma in the Rituximab. MJR Era: Results of an F 2 -Study Database. JCO 2012; 30: 3848
至新治�开始的�� MJR Ardeshna KM et al. ASH 2010 Abstract 6
至治�失�的�� (R-CHOP vs R-CVP vs R-FM) MJR Federico M, et al. ASCO 2012: Abstract 8006
不良事件(≥ 3�) (R-CHOP vs R-CVP vs R-FM) MJR Federico M, et al. ASCO 2012: Abstract 8006
苯达莫斯汀-利妥昔�抗 (B-R) vs CHOP-R Sti. L NHL 1 -2003 苯达莫斯汀-利妥昔�抗 - 苯达莫斯汀 90 mg/m 2 day 1+2 - 利妥昔�抗 375 mg/m 2 day 1 �泡 Waldenström’s ��区 小淋巴�胞 套�胞(老年) 随机 CHOP-利妥昔�抗 - �磷�胺 750 mg/m 2 day 1 - 柔�霉素 50 mg/m 2 day 1 - �春地辛 1. 4 mg/m 2 day 1 - 强的松 100 mg days 1 -5 - 利妥昔�抗 375 mg/m 2 day 1 Lancet 2012, accepted for publication; J Clin Oncol 30, 2012 (suppl; abstr 3) Courtesy of Mathias Rummel
疾病种� 随机了549例患者。514例可用于�效、毒性�价。 B-R �� n CHOP-R 年� (中位) 261 253 64 �泡 54% 139 140 60 套�胞 18 % 45 48 70 ��区 13 % 37 30 66 Waldenströms 8% 22 19 64 小淋巴�胞淋巴瘤 4% 10 11 68 不能分� 2% 7 5 69 MJR Lancet 2012, accepted for publication; J Clin Oncol 30, 2012 (suppl; abstr 3)
患者特点 B-R CHOP-R (n=261) (n=253 年� (中位) 64 yrs 63 yrs > 70� 23 % IV期 77 % 骨髓 68 % 67 % B症状 38 % 29 % LDH > 240 U/l 38 % 34 % 大包� 27 % IPI > 2 37 % 34 % FLIPI 0 -1 FLIPI 2 FLIPI > 3 12 % 46 % 19 % 33 % 48 % n = 279 P value = 0. 0322 29 % MJR Courtesy of Mathias Rummel
血液学最低���果的 CTC不良事件分� �生占�体患者的比例 (%) 治�� 2� 3� 4� 3 -4� 白�胞 CHOP-R 39 (15) 110 (44) 71 (28) 181 (72) (109/L) B-R 80 (30) 85 (32) 13 (5) 98 (37) CHOP-R 19 (8) 70 (28) 103 (41) 173 (69) B-R 61 (23) 53 (20) 24 (9) 77 (29) CHOP-R 72 (29) 87 (35) 19 (8) 106 (43) B-R 38 (14) 122 (46) 74 (28) 196 (74) CHOP-R 84 (33) 10 (4) 2 (<1) 12 (5) B-R 44 (16) 6 (2) 2 (<1) 8 (3) 血小板 CHOP-R 20 (8) 11 (4) 5 (2) 16 (6) (109/L) B-R 19 (7) 15 (6) 2 (<1) 13 (5) 中性粒�胞 (109/L) 淋巴�胞 (109/L) 血�蛋白 (g/L) Courtesy of Mathias Rummel MJR
毒性 (所有CTC分�) B-R (n=261) CHOP-R (n=253) (患者数量) P value - +++ < 0. 0001 感�异常 18 73 < 0. 0001 口腔�� 16 47 < 0. 0001 皮肤(�斑) 42 23 = 0. 0122 �敏反�(皮肤) 40 15 = 0. 0003 感染性并�症 96 127 = 0. 0025 - �血症 1 8 = 0. 0190 脱� Courtesy of Mathias Rummel
�果 反�率 B-R CHOP-R (n=261) (n=253) ORR 92, 7 % 91, 3 % CR 39, 8 % 30, 0 % SD 2, 7 % 3, 6 % PD 3, 5 % 2, 8 % P � = 0. 021 MJR Lancet 2012 in press; J Clin Oncol 30, 2012 (suppl; abstr 3)
PFS: �泡 (n=279) 随� 45个月 1. 0 中位��(月) 0. 9 0. 8 B-R 未达到 CHOP-R 40. 9 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 危�度, 0. 61 (95% CI 0. 42 - 0. 87) 0. 1 p = 0. 0072 0. 0 0 12 24 36 48 60 72 84 96 月 Courtesy of Mathias Rummel MJR
PFS: �泡, FLIPI 低 (0 -2) (n=152; 54. 5%) 1. 0 中位��(月) 0. 9 0. 8 B-R 未达到 CHOP-R 46. 6 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 危�度, 0. 56 (95% CI 0. 31 - 0. 98) 0. 1 p = 0. 0428 0. 0 0 12 24 36 48 60 72 84 96 月 Courtesy of Mathias Rummel MJR
PFS: �泡, FLIPI 高 (3 -5) (n=127; 45. 5%) 1. 0 中位�� (月) 0. 9 0. 8 B-R 53. 4 CHOP-R 34. 9 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 危�度, 0. 63 (95% CI 0. 38 - 1. 04) 0. 1 p = 0. 0679 0. 0 0 12 24 36 48 60 72 84 96 月 Courtesy of Mathias Rummel MJR
PFS: LDH 正常 ( < 240 U/l ) ( n = 330 ) 1. 0 中位��(月) 0. 9 0. 8 B-R 73. 0 CHOP-R 34. 6 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 危�度, 0. 48 (95% CI 0. 34 - 0. 67) 0. 1 p < 0. 0001 0. 0 0 12 24 36 48 60 72 84 96 月 Courtesy of Mathias Rummel MJR
PFS: LDH 升高 ( > 240 U/L ) ( n = 184 ) 1. 0 中位�� (月) 0. 9 0. 8 B-R 40. 0 CHOP-R 30. 9 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 危�度, 0. 74 (95% CI 0. 49 - 1. 08) 0. 1 p = 0. 1182 0. 0 0 12 24 36 48 60 72 84 96 月 Courtesy of Mathias Rummel MJR
年�: 61�及以上 ( n = 315 ) 1. 0 中位�� (月) 0. 9 0. 8 B-R 53. 6 CHOP-R 31. 5 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 危�度, 0. 62 (95% CI 0. 45 - 0. 84) 0. 1 p = 0. 0022 0. 0 0 12 24 36 48 60 72 84 96 月 Courtesy of Mathias Rummel MJR
年�: 60�及以下 ( n = 199 ) 1. 0 中位�� (月) 0. 9 0. 8 B-R 71. 6 CHOP-R 30. 9 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 危�度, 0. 52 (95% CI 0. 33 - 0. 79) 0. 1 p = 0. 0022 0. 0 0 12 24 36 48 60 72 84 96 月 Courtesy of Mathias Rummel MJR
�体生存 1. 0 0. 9 0. 8 B-R 0. 7 0. 6 CHOP-R 0. 5 0. 4 0. 3 2年 3年 4年 5年 6年 7年 0. 2 89. 7% 85. 6% 82. 3% 80. 1% 75. 9% 0. 1 89. 5% 86. 7% 84. 2% 77. 8% 75. 5% 59. 5% 24 36 0. 0 0 12 48 60 72 84 96 月 Courtesy of Mathias Rummel MJR
�泡淋巴瘤中的死亡之吻 Ramsay, et al. Blood 2010 Laurent, et al. Blood 2011
来那度胺和利妥昔�抗治�初 治惰性淋巴瘤:II期�床��的 最后�果 Nathan Fowler, Sattva Neelapu, Frederick Hagemeister, Peter Mc. Laughlin, Larry W Kwak, Jorge Romaguera, Michele Fanale, Luis Fayad, Robert Orlowski, Michael Wang, Francesco Turturro, Yasuhiro Oki, Linda Lacerte, Felipe Samaniego Department of Lymphoma/Myeloma MD Anderson Cancer Center, Houston, Texas Courtesy of Nathan Fowler
反�率 全体患者 Eval ITT (N=103) (N=110) SLL (N=30) MZL (N=27)* FL (N=46)* ORR, n (%) 24 (80) 24(89) 45(98) 93(90) 93(85) CR/Cru 8(27) 18(67) 40(87) 66(64) 66(60) PR 16(53) 6(22) 5(11) 27(26) 27(25) SD, n (%) 4(13) 3(11) 1(2) 8(8) 8(7) PD, n (%) 2(7) 0 0 2(2) *7例患者不能�价 • 5 例由于第 1周期的不良事件 • 1 例由于�背方案 • 1 例由于撤回知情同意 Courtesy of Nathan Fowler
无�展生存 全体可�价的患者 N=103 36个月PFS*: 78% *��的 3年 PFS Courtesy of Nathan Fowler
≥ 3�血液学毒性 100% 90% 80% 70% Grade 4 Grade 3 60% 50% 41% 40% 30% 20% 6% 0% 10% 0% NEUTROPHILS (ANC/AGC) PLATELETS HEMOGLOBIN • 5例患者出� 3�中性粒�胞减少并��
PA F IN AT (M IGU U SC E N LE AU ) R AS C DIA SE H ON RR A /D S ES TI HE Q PA A U AM TIO AT N D IO R Y N D EY YS E D PN I ED ZZI EA BL N U EM ES R R A: L S ED I M B M VIS M U EM C ION O O SI R T Y IM F IS PA EV N W IR ER EU AT M R ER EN O PA Y T P TH R EY PA Y: UR E SE ITU I C YT E N ( N SO S O DE HE V KI M A D O R N E A: H /H MI Y E T R EL EA AD ING N EA D A AC EU S N H R E S D N E) O PA YN EC K T D IN HY RO FE : M ME C TI OT O OR N PA (U IN RI (N ) O C S) O U G H 全部非血液学不良事件(�生率>10%) 100% 90% 80% 70% 60% 50% 40% 30% Grade 4 20% Grade 3 10% Grade 2 0% Grade 1 • 在 48%的患者�察到皮疹,一般��度,可以自限。
FL患者生存:斯坦福的��,1960 -2003 Rituximab era Aggressive chemo/ Purine analogue Anthracycline Pre- anthracycline MJR
FL��生存vs�期生存的比� MJR Tan D, et al. J Clin Oncol 2008 (suppl; abstr 8535)
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Rituximab era Aggressive chemo/ Purine analogue Anthracycline Pre- anthracycline MJR
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