SCIENTIFIC PROGRAMME
SESSION I
THE GENOMIC AND
EPIGENOMIC LANDSCAPE
OF CLL AND CLINICAL
CONSEQUENCES
SESSION II
THE ROLE OF BCR
ACTIVATION AND
SIGNALLING FOR CLL
SESSION III
THERAPEUTIC OPTIONS
FOR CLL
SESSION IV
LONG TERM FOLLOW
UP OF CLINICAL TRIALS
VERSUS REAL WORLD
DATA (OUTSIDE CLINICAL
TRIALS DATA-OCT)
SESSION V
THE INCREASING ROLE
OF THE LEUKAEMIC
MICROENVIRONMENT
SESSION VI
THERAPEUTIC OPTIONS 2 :
THE USE OF CELLULAR
AND NON-CELLULAR
IMMUNOTHERAPIES IN
CLL
SESSION VII
EFFICACY THROUGH
SAFETY
SESSION VIII
CLONAL HETEROGENEITY,
CLONAL EVOLUTION AND
MECHANISMS OF DRUG
RESISTANCE
SESSION IX
CONTRASTING
THERAPEUTIC CONCEPTS
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
FACULTY DISCLOSURES
The iLLUMINATE phase III study designed to compare ibrutinib-obinutuzumab to what has
been considered for years the standard of treatment in the elderly in first line, chlorambucil-obinutuzumab,
showed a superior PFS for the BTKi combination treatment.8 This was mostly
evident in patients showing high risk genomic features and patients with bulky disease (> 5
cm). With a longer follow-up of median 40.6 m the median PFS was not reached in the whole
population not even those at high risk.9
Recently 2 randomized studies, ECOG 1912 and Alliance, comparing ibrutinib based treatment
with immunochemotherapy (FCR or BR) confirmed the superiority of the BTKi treatment in
terms of PFS.10,11 The benefit was significant in patients with an unmutated IGHV status.
Ibrutinib rituximab when compared to FCR also showed an advantage on OS that was also
confirmed at the extended follow-up of 48 months.12
In the study with the longest follow-up, 7 years, rate of disease progression was higher in the
R/R setting when compared to patients treated in first line (6% versus 35%) and this is similar
when considering data from the Resonate and Resonate 2 trials. The rate of discontinuation
due to disease progression is similar when considering untreated or previously treated
patients ranging from 16.4% to 23%. In all the studies no new or unexpected AEs were
observed during follow-up, and the occurrence of most grade ≥3 AEs and serious AEs
decreased over time, with the exception of hypertension. Dose hold and dose reductions due
to AEs decreased over time and allowed to continue treatment and to receive benefit from
the BTKi.3,5,7
References
1. Byrd JC, O'Brien S, James DF Ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med.
2013;369:1278-9.
2. O'Brien S, Furman RR, Coutre SE, et al. Ibrutinib as initial therapy for elderly patients with
chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre,
phase 1b/2 trial. Lancet Oncol. 2014;15:48-58.
3. Byrd JC, Furman RR ,Coutre S et al. Up to 7 Years of Follow-Up of Single-Agent Ibrutinib in the
Phase 1b/2 PCYC-1102 Trial of First-Line and Relapsed/Refractory Patients With Chronic
Lymphocytic Leukemia/Small Lymphocytic Lymphoma.Blood. 2018;132(Supplement 1):3133.
4. Byrd JC, Brown JR, O’Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic
lymphoid leukemia. N Engl J Med. 2014;371:213–223.
5. Munir T, Brown JR, O'Brien S, et al. Final analysis from Resonate: Up to six years of follow-up
on ibrutinib in patients with previously treated chronic lymphocytic leukemiaor small
lymphocytic lymphoma. Am J Hematol. 2019;94:1353-1363
6. Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic
lymphocytic leukemia. N Engl J Med. 2015;373:2425–2437.
7. Burger JA, Barr PM, Robak T et al. Long-Term Efficacy and Safety of First-Line Ibrutinib
Treatment for Patients With CLL/SLL: 5 Years of Follow-Up From the Phase 3 RESONATE-2 Study.
2019 Leukemia in press.
8. Moreno C, Greil R, Demirkan F,et al. Ibrutinib plus obinutuzumab versus chlorambucil plus
obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a
multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:43-56.
9. Moreno C, Greil R, Demirkan F et al. Ibrutinib Plus Obinutuzumab Versus Chlorambucil Plus
Obinutuzumab as First-Line Treatment in Patients With Chronic Lymphocytic Leukemia or Small
Lymphocytic Lymphoma: Up to 4 Years of Extended Follow-Up From the Phase 3 iLLUMINATE