HematologyIOSI - Oncology Institute of Southern Switzerland

IOR - Institute of Oncology ResearchUSI – Universita’ della Svizzera Italiana

Bellinzona - Switzerland

Davide Rossi, M.D., Ph.D.

Chronic lymphocytic leukemia

Conflict of interest

Research Support:Janssen, Gilead, Abbvie, AstraZeneca, Cellestia,

Xeneticbio

Employee No

Consultant No

Major Stockholder No

Speakers Bureau No

Honoraria Gilead, Abbvie, Janssen, Roche, AstraZeneca, Loxo

Scientific Advisory Board Gilead, Abbvie, Janssen, AstraZeneca, MSD, Loxo, Verastem

First-line setting

• ELEVATE TN study

• CLL14 update

Results from ELEVATE TN study

Results from ELEVATE TN study

Results from ELEVATE TN study

Results from ELEVATE TN study

Results from ELEVATE TN study

Results from ELEVATE TN study

Results from ELEVATE TN study

Follow-up data from CLL14

CLL14 study design

CLL14: patients’ characteristics

Follow-up data from CLL14: PFS at 39.6 months

Follow-up data from CLL14

Follow-up data from CLL14: IGHV status

Follow-up data from CLL14: TP53 disruption

Follow-up data from CLL14: OS

Follow-up data from CLL14: MRD by ASO-PCR

Follow-up data from CLL14: MRD by NGS

Follow-up data from CLL14: MRD longitudinal evaluation

Follow-up data from CLL14: MRD and PFS

Follow-up data from CLL14: MRD and PFS

Follow-up data from CLL14: conclusions

Relapsed/refractory setting• MURANO update

MURANO study: updated analysis at 48 months

MURANO study: patients’ characteristics at baseline

MURANO study: updated analysis at 48 months

MURANO study: updated PFS analysis at 48 months

MURANO study: MRD status at EOT

MURANO study: EOT uMRD correlates with PFS

MURANO study: updated analysis at 48 months

MURANO study: OS benefit post-EOT

MURANO study updates

MURANO study updates

MURANO study updates

MURANO study updates

MURANO study updates

Question 1

Progressive previously untreated CLL patient, unfit, withconcomitant cardiac conditions, IGHV unmutated status, TP53 wildtype, limitations in logistics. What treatment would you consider asfirst choice (irrespective of reimbursement status in CH)?

1. Ibrutinib (+/-G)2. Clb+G3. VenG4. Acalabrutinib+G

Question 2

Progressive previously untreated CLL patient, unfit, withoutconcomitant cardiac conditions, IGHV unmutated, TP53 wild type,limitations in logistics. What treatment would you consider as firstchoice (irrespective of reimbursement status in CH)?

1. Ibrutinib (+/-G)2. Clb+G3. VenG4. Acalabrutinib+G

Question 3

Progressive previously untreated CLL patient, unfit, , withconcomitant cardiac conditions, IGHV unmutated status, TP53 wildtype, without limitations in logistics. What treatment would youconsider as first choice (irrespective of reimbursement status inCH)?

1. Ibrutinib (+/-G)2. Clb+G3. VenG4. Acalabrutinib+G

Question 4

Progressive previously chemoimmunotherapy treated CLL patient,TP53 wild type, PR with detectable MRD after 2 years of VenR.Which approach would you consider now (irrespective ofreimbursement status in CH)?

1. Stop treatment and watch and wait until clinical progression2. Switch to BTKi3. Maintenance with Venetoclax monotherapy4. Depends of MRD kinetics under Venetoclax treatment