PF386 HYPERTENSION IN PATIENTS TREATED WITH IBRUTINIB FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
Authors: Roeker L. , Yazdy M. , Gashonia L. , Goodfriend J. , Narkhede M. , Rhodes J. , Kennard K. , Morse H. , Dorsey C. , Battiato K. , Peterson M. , Carver J. , Schuster S. , Cheson B. , Mato A. 
Published: June 2019

Background:

Hypertension (HTN) is the most common grade ≥ 3 Ibrutinib (Ibr)‐associated adverse event (AE) observed in clinical trials (26%) (O’Brien, Blood 2015). Meta‐analysis of clinical trial data suggests a 2.8‐fold increased risk of HTN for patients (pts) treated with Ibr vs. placebo (Caldeira, PLOS ONE 2019). In clinical practice, data regarding incidence, medication management, and long term vascular consequences of Ibr‐associated HTN are limited. As Ibr is administered in a continuous fashion and HTN incidence is cumulative, this toxicity is presently understudied.

Aims:

To describe the incidence of HTN, as well as baseline comorbidities, change in blood pressure (BP) over time, and changes in cardiovascular (CV) medications for CLL pts treated with Ibr in routine clinical practice.

Methods:

Multicenter, retrospective cohort study of CLL pts treated with 420 mg Ibr for at least 6 months. We collected baseline CV comorbidities, baseline CV medications, BP measurements prior to Ibr initiation and sequentially following exposure at specific time points over a 12‐month period, and adjustments to CV medications in response to Ibr‐associated HTN (up or 1 year). Incident HTN is defined as BP > 140/90 mmHg, and worsening BP control is defined as sustained rise in SBP or DBP ≥ 3 mmHg over baseline.

Results:

We identified 247 Ibr treated CLL pts. Pre‐Ibr CV comorbidities included: HTN (43%), hyperlipidemia (35%), diabetes (16%), coronary artery disease (CAD; 9.7%), heart failure (2.0%), valvular heart disease (2.8%), atrial fibrillation (Afib; 4.5%), other arrhythmia (6.5%), stroke (2.8%), and smoking history (42%). At least one anti‐HTN medication was used in 51% prior to Ibr initiation (median number of meds 1, range 0–6, 33% ≥ 2 meds). Median BP prior to Ibr exposure was 127/71 mmHg (range 92–174/48–95) and median pulse 75 bpm (range 27–110). Median peak BP following Ibr exposure was significantly elevated (153/80 mmHg range 105–218/53–121, p < 0.0001). Median time to peak BP was 6 months (range 0–35 months). Figure 1 depicts median systolic BP at baseline and 1, 3, 6, 9, and 12 months following Ibr initiation. During the observation period, 36% and 84% experienced new HTN or worsening of existing HTN respectively. 19.8% of pts required initiation of at least one new anti‐HTN medication, and 4.7% required increased dose of a pre‐Ibr anti‐HTN medication. Of the 49 pts who required BP management, 86% started 1 new agent, and 14% started ≥2 new agents. The most common new classes of agents selected were beta blockers (32%), angiotensin receptor blockers (21%), diuretics (19%), calcium channel blockers (14%), and angiotensin converting enzyme inhibitors (14%). Regarding CV events following Ibr initiation, 6.4% experienced new onset Afib, 1.6% had CAD. Preexisting CV comorbidities, smoking history, and diabetes were not predictive of HTN development in univariate analysis.

Summary/Conclusion:

HTN is a pervasive AE of Ibr affecting pts with and without baseline HTN or CV conditions. Physiologically, systolic blood pressure appears to be more significantly affected than diastolic blood pressure. While these data demonstrate 20% of pts adjust current anti‐HTN meds or start new ones, it is not known how effective current management is at controlling this AE or preventing long term vascular events. In addition, we demonstrate that the proportion of pts initiating new anti‐HTN meds appears to be significantly lower than those experiencing new/worsening HTN, identifying a potential opportunity for care optimization in partnership with cardio‐oncology.

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