selecting therapy in cll
DESCRIPTION
A presentation on selecting first line therapy in CLL and how that influences subsequent therapy selection.TRANSCRIPT
CLL: Past, Present, and Future
Jeff Sharman M.D.Medical Director Hematology Research
US Oncologyhttp://cll-nhl.com
• Historical perspectives• FCR – The rise and fall• Choosing first line therapy in 2014• Management of relapsed disease• Ibrutinib considerations
CLL: Management in a TKI World
• Historical perspectives• FCR – The rise and fall• Choosing first line therapy in 2014• Management of relapsed disease• Ibrutinib considerations
CLL: Management in a TKI World
Chlorambucil
Fludarabine
FCR
1999-2003 at MDA
Improved Outcomes with FCR (2008)
German CLL8 – FC vs FCR (2003)
MDA Long Term Follow Up
So what is the problem?
FCR not so popular….
Patterns of Care (FCR in Front Line)
•Age < 65 = 45% FCR•Age 65-75 = 32% FCR•Age > 75 = 20% FCR
Clinical trials versus real life
• MDA FCR Median Age– 57 years old
• German CLL8 (FC vs FCR)– 61 years old
• Real life– Age 71 at diagnosis– Age 74 at first treatment
Age Matters
• Decreased Renal Function – Clears fludarabine
• Decreased Marrow Reserves– Prolonged cytopenias– MDS / AML
• Infectious Complications– Really nasty gross stuff
MDA Long Term follow up
Death within 12 months of first line therapy
• MDA = 1%• German CLL8/10 study = 3-4%
• Registry Studies = 10%
Case Study• 72 year old retired lumber yard worker
– Lymphocytosis c/w CLL stage I, but over 2 years progressive adenopathy and hemoglobin down to 10
– Deletion 13q but unmutated IgVH
• Entered onto FCR vs PCR study– Stopped FCR after cycle 3 due to myelotoxicity– Has maintained remission for six years
• Multiple treatment complications– Pulmonary aspergillosis– Received > 50 units PRBC’s over next two years– Now has MDS
Where will FCR fit in the next five years?
”We’re going to get rid of FCR”
German CLL10 StudyFCR versus BR
CIRS < 7, Creatinine Clearance > 70, no 17P deletion
FCR BR
ORR 97.8% 97.8%
CR 47% 38%
MRD Negative 71% 66%
2 Year PFS 85% 78%
German CLL10 StudyFCR versus BR
CIRS < 7, Creatinine Clearance > 70, no 17P deletion
FCR BR
G3/4 Neutropenia 82% 56%
G3/4 Infection 47% 26%
Induction Death 4% 2%
Complete 6 cycles 70% 80%
CLL10 Summary
• FCR works a little better, but considerably more toxic than BR
• No clear winner as gains in response offset by increased toxicity
What about the elderly?
Complement 1Chlorambucil +/- Ofatumumab
Chlorambucil Clb-Ofatumumab
PFS (mo) 13 22
ORR 69% 82%
CR 1% 12%
MRD 4% 12%
• Historical perspectives• FCR – The rise and fall• Choosing first line therapy in 2014• Management of relapsed disease• Ibrutinib considerations
CLL: Management in a TKI World
Choosing first line therapy in 2014
Age & Comorbidity
FCR BR Obi
• Historical perspectives• FCR – The rise and fall• Choosing first line therapy in 2014• Management of relapsed disease• Ibrutinib considerations
CLL: Management in a TKI World
What is “one prior therapy?”
MRD in CLL8 Study
Post 3 cycles End of Treatment
MRD: Depth = Duration
New Mutation Markers
CLL: Beyond FISH
CLL – Evolution in Real Time
A: Pre-ChlorambucilB: Pre FCRC: Post FCRD: Pre OfatumumabE: Post Ofatumumab
• Historical perspectives• FCR – The rise and fall• Choosing first line therapy in 2014• Management of relapsed disease• Ibrutinib considerations
CLL: Management in a TKI World
Clinical Challenges
• Initial lymphocytosis• Interruptions (surgery / other)
• Adherence• Copayments
• Adventures in medical decision making• Progressions
Clinical Challenges
• Initial lymphocytosis• Interruptions (surgery / other)
• Adherence• Copayments
• Adventures in medical decision making• Progressions
Compartment Effect: Decreased Nodes with Lymphocytosis
Lymphocytosis
FR
BR
Ibrutinib
Clinical Challenges
• Initial lymphocytosis• Interruptions (surgery / other)
• Adherence• Copayments
• Adventures in medical decision making• Progressions
Long Term Drug Problems?
Clinical Challenges
• Initial lymphocytosis• Interruptions (surgery / other)
• Adherence• Copayments
• Adventures in medical decision making• Progressions
Clinical Challenges
• Initial lymphocytosis• Interruptions (surgery / other)
• Adherence• Copayments
• Adventures in medical decision making• Progressions
Thank Youhttp://cll-nhl.com