1. Dr Parag Jasani Consultant Haematologist UCLH
Cure in CLL?
Dr Parag Jasani
Consultant Haematologist UCLH

2. Incurable!!

3. I know, I am the Doctor

4. MRD Negativity

5. What is MRD Negativity?
Why is MRD Negativity important?
How do we achieve this? Where are we yet?

6. What is MRD Negativity
No CLL cells detected by using CURRENT high resolution techniques

8. 1992
First reported assessment of MRD by Flow
Detection limit 10-4

9. MRD by PCR
MRD by RT-PCR Detection limit 10-6
Time consuming
Expensive

11. Previously Untreated CLL
Purine nucleosides
- Fludarabine
- Pentostatin
- Cladribine
5% - 20% CR
Better PFS in
younger pts
Chemo-immunotherapy (CIT)
45% CR; better PFS & OS
Alemtuzumab monotherapy
24% CR
Bendamustine
30% CR
Purine nucleosides
and alkylators
30% CR
Better PFS
Novel Targeted
Alkylating agents
- Chlorambucil
- Cyclophosphamide
Novel Targeted Therapies
(BCR, BCL2, IMiDs, ?) +
Monoclonal Antibodies
5% CR 11

12. Why is MRD Negativity important

13. Deeper responses= Longer survival
Marker of Prognosis
Targets for future treatment

15. Stopping therapy

18. MURANO EFFICACY RESULTS PB MRD Negativity
Table of Contents
PD/Death/Withdrew
Assay negative
Assay positive
Assay failure
Missing sample
Month
Month
MRD negative,
n (%): 88
121
117
110
116
(45)
(62)
(60)
(57)
MRD negative,
n (%): 11 26 20 17 10
(6)
(13)
(10)
(9)
(5)
At 9 months, MRD(neg) rates in PB were 62% for patients treated with VenR versus 13% for patients treated with BR.
Data Cutoff: May 8, 2017.
BR=Bendamustine+Rituximab. MRD=Minimal Residual Disease. PB=Peripheral Blood. PD=Progressive Disease. VenR=Venetoclax+Rituximab.
Seymour JF, et al. N Engl J Med. 2018;378(12):
AXONC171816(1)
Date of Preparation: May 2017

20. iFCG- MD Anderson IgVH mutated patients iFCG X 3cycles
Followed by Ibrutinib + Obinatuzumab X cycles Ibrutinib.
STOP at 12 months if MRD Neg
85-90% MRD Neg

22. Combination Rituximab Obinatuzumab Ibrutinib Venatoclax BendamustineFC

23. Other Treatments to achieve MRD Negativity or Cure
CAR-T
BiTE ( Bivalent antibody e.g. Blinatumumab)
Allogeneic Transplant

24. Key Points Use of these drugs earlier in treatment
Sequential use to aim for complete disease eradication.
COST!!!!

25. Questions/ Discussions