Question: Is there a role of biologic prognostic markers in the - - PowerPoint PPT Presentation

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Question: Is there a role of biologic prognostic markers in the - - PowerPoint PPT Presentation

May 22, 2023 214 likes •386 views

Question: Is there a role of biologic prognostic markers in the treatment of CLL? YES: Robin Foa NO: Kanti Rai Kanti R. Rai 1 1 Relevant References Hallek et al, Blood 2008, New Guidelines. Weidra et al, JCO 2009, Beta-2, Age

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Question: Is there a role of biologic prognostic markers in the treatment of CLL? YES: Robin Foa NO: Kanti Rai

Kanti R. Rai

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Relevant References

  • Hallek et al, Blood 2008, New Guidelines.
  • Weidra et al, JCO 2009, Beta-2, Age
  • Grever et al, JCO 2007, FC vs F
  • Shanafelt et al, Blood 2004, Need to

develop model

  • Montserrat, Blood 2006, Refractory CLL
  • Gribben, Blood 2010, Follow IWCLL
  • Orlandi et al, Haematologica 2009; 94:S46.
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Biological Prognostic Markers

  • FISH Cytogenetics
  • IGHV Mutation Status
  • Zap-70 Status
  • CD-38 Status
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FISH

FISH Cytogenetics enable us to divide CLL patients into three risk categories:

RISK CATEGORIES Low Intermediate High BY FISH Del 13q, None detectable Trisomy 12 Del 11q, Del 17p

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IGHV

IgHV gene mutation testing yields two broad categories of risk Low Risk Mutated (>2%) High Risk Unmutated

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CD-38

CD 38 Co-Expression on CLL lymphocytes yields two broad categories of risk: Low Risk CD38 Negative High Risk CD38 Positive

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Zap-70

ZAP-70 expression testing on CLL lymphocytes yields two broad categories

  • f risk:

Low Risk ZAP-70 Negative High Risk ZAP-70 Postiive

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CD38- CD38+

C D

0 2 4 6 8 10121416182022 20 40 60 80 100

ZAP-70- (9.7 yrs) N=121 ZAP-70+ (2.7 yrs) N=38 p<0.0001*

2 4 6 8 10 12 14 16 20 40 60 80 100

ZAP-70- (<15 yrs) N=46 ZAP-70+ (3.4 yrs) N=29 p<0.0001*

M-IGHV

Time (yrs) % without treatment

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Rassenti Conclusions

Three prognostic markers analyzed Multivariate analysis: ZAP-70 was the strongest including in early stage, asymptomatic disease, mutation status and CD38 did not improve predictive power of ZAP-70 negative patients for time to first treatment.

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Orlandi EM,et al Haematologica 2009;94:S 46

Binet Stage A patients N=329:At 4 yrs (med f/u) 37% required tx. Unfavorable FISH: 9% CD38 Positive: 13 to 38% ZAP-70 Positive: 21% Multivariate: Only mutation status was independent predictor of Treatment-Free-Interval (TFI)

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Orlandi Conclusions

Concordance Data & TFI 18 years F/U

Concordant/Favorable (44%) ~96 mos. Concordant/Unfavorable (11%) 29 mos. Discordant (44%) 54 mos. Orlandi et al 2009

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Late Stage CLL Patients

  • Usually have one or the other bad

prognostic markers:

– Unmut/ZAP/38/11q-, 17p- and/or High Beta-2, Short LDT, Symptoms

  • There is no dispute here in making

sense of the new markers.

But did new markers add anything?

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Early-Stage CLL Patients

  • Have about 40% likelihood of discordant

(new) markers:

– FISH/Mut/ZAP/38/Symptoms/LDT

  • The question, when treating these patients

is “How to make sense of prognostic markers?” This becomes most pertinent, and most vexing

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Reference Guidelines:

  • Weirda 2009: Created a model, Beta-2, age
  • Grever 2007: FC vs F, new markers little value
  • Shanafelt 2004: Need to build model
  • Montserrat 2006: New markers not necessary in

Refractory disease

  • Orlandi 2009: Discordance rampant, confuses
  • Hallek 2008: New Guidelines IWCLL
  • Gribben 2010: Follow IWCLL Guidelines
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Discordant markers are a reality

Qu: How to Make Sense? Ans: Use Common Sense! Use your clinical judgment!!