Management of untreated cll for web (2015)
-
Upload
jeff-sharman -
Category
Health & Medicine
-
view
6.518 -
download
0
Transcript of Management of untreated cll for web (2015)
![Page 1: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/1.jpg)
Management of Untreated CLL2015
Jeff Sharman M.D.Medical Director Hematology Research
US Oncology
![Page 2: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/2.jpg)
Long Term Follow UpFCR at MD Anderson
![Page 3: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/3.jpg)
Selecting Therapy
Genomics
Fitness
![Page 4: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/4.jpg)
![Page 5: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/5.jpg)
![Page 6: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/6.jpg)
Genomics 2015
![Page 7: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/7.jpg)
Genomic Sequencing
![Page 8: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/8.jpg)
![Page 9: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/9.jpg)
![Page 10: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/10.jpg)
![Page 11: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/11.jpg)
Untreated CLL
High RiskIntermediate(Very) Low Risk
Maximal Tolerated Therapy
Do No Harm Novel Agents
IgHV MutatedNo Int/High
Risk
SF3B1 / NOTCH1 / 11Q
IgHV Unmutated
17P / TP53BIRC3
![Page 12: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/12.jpg)
TP53 Gene Mutation 17P Deletion
![Page 13: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/13.jpg)
![Page 14: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/14.jpg)
![Page 15: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/15.jpg)
![Page 16: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/16.jpg)
Idelalisib in Untreated CLL
![Page 17: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/17.jpg)
High Risk CLL Summary
High risk CLL includes abnormal TP53 (del17P/mut) or BIRC3 mutation
These patients die quickly with traditional therapy
Novel agents most appropriate initial therapy in high risk CLL
![Page 18: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/18.jpg)
Untreated CLL
High RiskIntermediate(Very) Low Risk
Maximal Tolerated Therapy
Do No Harm Novel Agents
IgHV MutatedNo Int/High
Risk
SF3B1 / NOTCH1 / 11Q
IgHV Unmutated
17P / TP53BIRC3
![Page 19: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/19.jpg)
Untreated CLL
(Very) Low Risk
IgHV MutatedNo Int/High
Risk
Super Fit
Fit
Unfit
FCR
BR / BG
Gazyva
![Page 20: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/20.jpg)
Can CLL be Cured?
MD Anderson CLL8 FCR vs FC
![Page 21: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/21.jpg)
FCR vs BR in IgHV Mutated
Improved FCR outcomes only age < 65
Greater neutropenia and infection
More durable immune dysfunction
Greater secondary malignancy
![Page 22: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/22.jpg)
What is Fitness?
• Median age MDA = 57• Median age CLL8 = 61• Median age SEER = 71
• Age associated with:– Higher comorbidity– Lower renal function– More advanced disease
at treatment initiation
• Approximately 20% CLL patients meet enrollment criteria for CLL 8/10 at first line rx
![Page 23: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/23.jpg)
Mortality Following First Line Therapy
Setting Median Age Regimen 12 Month Mortality
MD Anderson 57 FCR 1%
German CLL8 61 FCR vs FC 4%
Community 74 Any 10%
![Page 24: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/24.jpg)
German CLL11 Study
![Page 25: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/25.jpg)
German CLL11 Study
![Page 26: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/26.jpg)
German CLL11 Study
![Page 27: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/27.jpg)
Single Agent Gazyva
![Page 28: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/28.jpg)
Overall Approach in Low Risk CLL
![Page 29: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/29.jpg)
Low Risk Summary• (Very) Low risk CLL lacks 17P/11Q deletions or NOTCH1, SF3B1,
BIRC3, TP53 mutations
• When treated aggressively, high fraction with durable response, many possibly cured
• Benefit of FCR primarily in patients with most favorable genomics and ideal fitness with age less than 65
• Obinutuzumab is more effective than rituximab and is appropriate therapy in patients not suitable for chemoimmunotherapy – or in combination with bendamustine on this trial
![Page 30: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/30.jpg)
Untreated CLL
High RiskIntermediate(Very) Low Risk
Maximal Tolerated Therapy
Do No Harm Novel Agents
IgHV MutatedNo Int/High
Risk
SF3B1 / NOTCH1 / 11Q
IgHV Unmutated
17P / TP53BIRC3
![Page 31: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/31.jpg)
FCR vs BR – When Better isn’t Best
![Page 32: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/32.jpg)
Untreated CLL
High RiskIntermediate(Very) Low Risk
Maximal Tolerated Therapy
Do No Harm Novel Agents
IgHV MutatedNo Int/High
Risk
SF3B1 / NOTCH1 / 11Q
IgHV Unmutated
17P / TP53BIRC3
![Page 33: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/33.jpg)
How I Manage Untreated CLL
High risk patients (17P/TP53/BIRC3) are treated with novel agents preferably on trial
Low risk patients (No high/int risk markers) are treated with maximal tolerated therapy. In community setting FCR use is uncommon
Intermediate risk patients (no high risk, but have an intermediate marker such as 11Q/SF3B1/NOTCH1/IgHV unmutated) do not receive FCR but get either BR (BG) or Gazyva
![Page 34: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/34.jpg)
Using Gazyva
Infusion reactions / management
First cycle cytopenias
Lymphocyte clearance kinetics
Growth factor support
![Page 35: Management of untreated cll for web (2015)](https://reader036.fdocuments.in/reader036/viewer/2022062308/55c79b78bb61ebd16f8b45cd/html5/thumbnails/35.jpg)
Questions?