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
JENNIFER WOYACH (COLOMBUS)
IBRUTINIB
With short term follow-up from patients on ibrutinib, it appeared that all patients would
benefit from inhibition of the B cell receptor signaling pathway/Bruton’s Tyrosine Kinase
(BTK). However, while many patients do enjoy long remissions with these agents, including
ibrutinib and acalabrutinib, with longer follow-up it has become apparent that our traditional
high risk genomic features are important even with these very effective therapies.
The first prognostic marker that was associated with shorter remissions in ibrutinib-treated
patients was complex karyotype, defined as 3 or more cytogenetic abnormalities on
stimulated karyotype. In 2 large single-institution studies of patients with predominantly
relapsed disease, complex karyotype was shown to be the strongest predictor of
discontinuation of ibrutinib due to disease progression manifested as either CLL progression
or Richter’s Transformation. 1 2 With longer follow-up, this association has remained true. 3 4
Interestingly, in the frontline setting with relatively limited follow-up, complex karyotype does
not appear to be associated with progression. 5 Longer follow-up will be needed to explore
this further, however, it could reflect a different disease biology of complex karyotype
between those with previously untreated CLL and those with highly refractory disease.
Abnormalities of TP53, reflected by either mutation or del(17p) on FISH, have also been shown
to be independently associated with progression of CLL, especially for patients treated in the
relapsed setting. 6 3 7 4 Del(11q22.3), however, which has traditionally been a marker of poor
prognosis in CLL, does not appear to have relevance for patients treated with ibrutinib. 8
Beta 2 microglobulin (B2M) is another traditional CLL prognostic factor, where high levels of
B2M have been associated with aggressive disease. 9 With ibrutinib treatment, as in many
other clinical scenarios, the data with B2M is conflicting, with some groups noting an
association with higher B2M and inferior outcomes, 7 and others not. 2 Further, one group has
shown that normalization of B2M by 6 months of ibrutinib therapy is associated with longer
progression free survival (PFS), while failure to normalize B2M at 6 months was associated
with shorter PFS. 10
Overall, with now thousands of patients treated with ibrutinib with significant follow-up, we
can better understand prognostic features associated with shorter and longer remission
durations. Continued study will be needed to understand whether risk calculators, such as
the CLL IPI or others are of utility in these patients and can help guide therapy decisions.
References
1. Thompson PA, O'Brien SM, Wierda WG, et al. Complex karyotype is a stronger predictor than
del(17p) for an inferior outcome in relapsed or refractory chronic lymphocytic leukemia
patients treated with ibrutinib-based regimens. Cancer. 2015;121(20):3612-3621.
2. Maddocks KJ, Ruppert AS, Lozanski G, et al. Etiology of Ibrutinib Therapy Discontinuation and
Outcomes in Patients With Chronic Lymphocytic Leukemia. JAMA oncology. 2015;1(1):80-87.
3. Woyach JA, Ruppert AS, Guinn D, et al. BTKC481S-Mediated Resistance to Ibrutinib in Chronic
Lymphocytic Leukemia. J Clin Oncol. 2017;35(13):1437-1443.