management of untreated cll for web (2015)
TRANSCRIPT
Management of Untreated CLL2015
Jeff Sharman M.D.Medical Director Hematology Research
US Oncology
Long Term Follow UpFCR at MD Anderson
Selecting Therapy
Genomics
Fitness
Genomics 2015
Genomic Sequencing
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
TP53 Gene Mutation 17P Deletion
Idelalisib in Untreated CLL
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
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
Untreated CLL
(Very) Low Risk
IgHV MutatedNo Int/High
Risk
Super Fit
Fit
Unfit
FCR
BR / BG
Gazyva
Can CLL be Cured?
MD Anderson CLL8 FCR vs FC
FCR vs BR in IgHV Mutated
Improved FCR outcomes only age < 65
Greater neutropenia and infection
More durable immune dysfunction
Greater secondary malignancy
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
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%
German CLL11 Study
German CLL11 Study
German CLL11 Study
Single Agent Gazyva
Overall Approach in Low Risk CLL
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
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
FCR vs BR – When Better isn’t Best
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
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
Using Gazyva
Infusion reactions / management
First cycle cytopenias
Lymphocyte clearance kinetics
Growth factor support
Questions?