EARLY DISCONTINUATION (ED) OF THERAPY AND TREATMENT PATTERNS AMONG
CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) PATIENTS: FINDINGS FROM A LINKED CLAIMS
AND ELECTRONIC HEALTH RECORD (EHR) DATASET
Seth Kuranz1, Sierra Luciano1, Jennifer Stacey1
1TriNetX, Inc., Cambridge, MA, United States
INTRODUCTIONThe Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib is used as first line of
therapy (LOT) and salvage therapy in chronic lymphocytic leukemia (CLL)
patients and in combination with chemotherapy, anti-CD20 biologics, and
venetoclax among other drugs. Several studies have shown that 10-20% of
patients receiving ibrutinib discontinue due to intolerance, disease progression,
transformation, or other causes. Those who discontinue due to disease
transformation or early disease progression are reported to have increased
mortality risk. This study was conducted to provide much-needed real-world
data (RWD) on CLL treatment patterns and treatment-related adverse effects.
METHODSCLL patients first diagnosed between 2012-2019 were identified in a 200 million
patient claims/EHR dataset. All patients were aged 18+, had two claims for CLL
submitted at least 1 week apart, and were treated with an antineoplastic
medication following diagnosis. All patient characteristics were defined using
ICD-9/10, CPT, RxNorm, and LOINC codes.
To examine treatment patterns, the start date of the first LOT was defined as
the time of the first treatment following the CLL diagnosis. All medications taken
within 28 days of the start date were grouped into a combination LOT. The
second and subsequent LOTs started when a new medication was identified in
a patient’s record or when 365 days passed without any record of a medication.
Time on treatment was defined as the number of months between the first and
most recent record of an ingredient in a patient’s EHR.
Early discontinuation (ED) was defined as any patients who discontinued their
first antineoplastic within the first month after the initial CLL diagnosis. The
frequency of diagnoses in the month before discontinuation were used to
examine potential reasons for discontinuation among the two largest treated
populations: patients treated with ibrutinib and patients treated with rituximab
and bendamustine (rit+bend). Patients who discontinued therapy were
compared to patients who continued with therapy (continuers), using the first
treatment recorded in the month after diagnosis as the index date in both
groups, and adjusting for demographics using a 1:1 matched propensity score
model. Following the index event, a Kaplan-Meier analysis measured the
event-free survival probability for anemia, transfusions, and all-cause mortality.
Figure 1. Proportion of patients treated with each ingredient
during the first LOT
RESULTSThe mean age at diagnosis of the 38,653 CLL patients identified in the dataset
was 70.4 (+10.7). In the first LOT, 67 unique ingredients were identified. The
most common medications included ibrutinib (21%), rituximab (20%),
bendamustine (9%), fluorouracil (6%), cyclophosphamide (5%), chlorambucil
(5%), and fludarabine (3%) (Figure 1). Most patients were treated with a single
LOT and did not progress to other medications. Among patients who
progressed from ibrutinib in the first LOT, other antineoplastics made up the
most common second LOT. Patients with an antineoplastic recorded in the first
LOT were more likely to switch to ibrutinib than any other therapy. Patients
treated with a combination of rit+bend most often switched to ibrutinib or other
antineoplastics as a second LOT.
Patients treated with ibrutinib remain on treatment for longer than patients
treated with rituximab and bendamustine. Among patients treated with ibrutinib,
the length of treatment decreased monotonically over two years (Figure 3). The
proportion of patients treated with rituximab dropped off substantially after 6
months (Figure 3).
In the month before the index treatment, ED patients treated with ibrutinib had a
higher prevalence of anemia, pain, and malaise/fatigue as compared to
continuers. Among rit+bend patients, characteristics were similar between
continuers and ED patients (Table 1). Among both ibrutinib and rit+bend treated
patients, continuers had a higher survival probability than ED patients (p<0.05)
(Figures 4 and 5). Continuers treated with ibrutinib were less likely to develop
anemia and receive a transfusion (p<0.05) (Figures 6 and 8).
Table 1. Patients characteristics among ED and continuer
patients treated with ibrutinib and rit+bend
CONCLUSIONSThe treatment landscape in CLL includes many off-label therapies including
monoclonal antibodies and other chemotherapies. However, most patients
remain on either ibrutinib or rit+bend for the length of care. Patients who do not
discontinue a therapy within the first month are less likely to develop
complications and have a lower probability of all-cause mortality. Further
research is needed to understand the dynamics of more complex treatment
pathways.
REFERENCESJain P, Thompson PA, Keating M, et al. Long-term outcomes for patients with
chronic lymphocytic leukemia who discontinue ibrutinib. Cancer.
2017;123(12):2268–2273. doi:10.1002/cncr.30596
DISCLOSURESAll authors are employed by TriNetX, Inc.
Figure 2. Month of most recent treatment of bendamustine
following the first treatment
Figure 3. Month of most recent treatment of ibrutinib and
rituximab following the first treatment
Figure 4. All-cause mortality among continuers and ED patients
treated with ibrutinib
Figure 5. All-cause mortality among continuers and ED patients
treated with rit+bend
Figure 6. Occurrence of anemia among continuers and ED
patients treated with ibrutinib
Figure 7. Occurrence of anemia among continuers and ED
patients treated with rit+bend
Figure 8. Occurrence of transfusions among continuers and ED
patients treated with ibrutinib
Figure 9. Occurrence of transfusions among continuers and ED
patients treated with rit+bend
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Ibrutinib Rituximab
ASH Annual Meeting 2019 | Orlando, FL United States
Ibrutinib Rit+bend
ED Continuers ED Continuers
n /
mean% / SD
n /
mean% / SD
n /
mean% / SD
n /
mean% / SD
Age at Index (mean / SD) 72.7 10.0 70.6 10.2 67.9 9.5 70.4 9.9
White (n / %) 753 30.7 2,208 28.4 653 21.8 249 23.0
Female (n / %) 895 36.5 2,909 37.4 993 33.1 392 36.2
Hemolytic anemias (n / %) 44 1.8 101 1.3 83 2.8 32 3.0
Aplastic and other anemias and other bone marrow
failure syndromes (n / %)320 13.1 705 9.1 525 17.5 205 18.9
Other anemias (n / %) 244 10.0 537 6.9 417 13.9 163 15.0
Anemia due to antineoplastic chemotherapy (n / %) 11 0.4 30 0.4 42 1.4 31 2.9
Anemia, unspecified (n / %) 232 9.5 491 6.3 377 12.6 138 12.7
Purpura and other hemorrhagic conditions (n / %) 166 6.8 480 6.2 334 11.1 118 10.9
Pain in joint (n / %) 64 2.6 145 1.9 57 1.9 12 1.1
Nausea and vomiting (n / %) 41 1.7 69 0.9 555 18.5 185 17.1
Malaise and fatigue (n / %) 144 5.9 314 4.0 259 8.6 100 9.2
Poisoning by, adverse effect of and underdosing of
antineoplastic and immunosuppressive drugs (n / %)14 0.6 43 0.6 144 4.8 65 6.00
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Surv
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