HSSP Leads to High Rate of Acid Suppression Therapy Substitution

The University of Rochester Specialty Pharmacy is an integrated health system specialty pharmacy (HSSP) that serves nearly 20 different clinical areas.

Integrated HSSPs focus on services outside the traditional dispensing role in collaboration with the interdisciplinary health care team. These services include benefits investigation, financial assistance evaluation, medication education and monitoring related to adherence, adverse reactions, drug interactions, labs, and other disease- or medication-specific monitoring parameters.

Wilmot Cancer Institute is part of the University of Rochester Medical Center and serves approximately 3 million patients diagnosed with cancer across Central and Western New York. To support the outpatient population treated within Wilmot Cancer Institute and prescribed oral anticancer therapy, the University of Rochester Specialty Pharmacy has 7 board-certified clinical pharmacists dedicated to the oncology specialty area.

Patients taking oral anticancer therapy are frequently in contact with their assigned clinical pharmacists and medication access specialists, who complete a financial assistance evaluation prior to starting therapy to mitigate out-of-pocket costs. Patients then meet with a clinical pharmacist prior to medication initiation, when a thorough medication reconciliation is completed to assess for interactions with OTC and prescribed medications.

If a drug interaction exists with the anticipated anticancer therapeutic agent, the pharmacist communicates with the primary oncologist to make any necessary medication adjustments. In addition, patients are followed regularly by clinical pharmacists during in-office clinic visits and follow-up telephone calls, which are completed in tandem with monthly refill assessments.

Study Introduction

A retrospective chart review was conducted at the University of Rochester Specialty Pharmacy to evaluate the clinical impact of concomitant proton pump inhibitor (PPI) therapy in patients treated with acalabrutinib (Calquence). Acalabrutinib is an oral Bruton tyrosine kinase inhibitor that is FDA approved for treatment-naïve and relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and relapsed/refractory mantle cell lymphoma.^1-3

Acalabrutinib solubility decreases with increasing pH, therefore the coadministra-tion of acalabrutinib with acid reducing agents decreases plasma concentrations and may decrease efficacy. The acalabrutinib prescribing information recommends avoiding PPIs and separating antacids or H2 receptor antagonists.^4,5

In clinical practice, if a patient does not have a successful trial with a PPI, providers may revert to PPI therapy despite the interaction. Although trials have been completed to determine coadministration recommendations based on under-the-curve measures, data are limited to assess the clinical impact of concomitant acalabrutinib and PPI use. This study aimed to evaluate the clinical impact of concomitant PPI therapy in patients treated with acalabrutinib therapy.

Methods

Adults diagnosed with CLL/SLL on acalabrutinib therapy for at least 3 months and treated at the Wilmot Cancer Institute between October 31, 2017, and September 15, 2020, were identified via electronic medical records (EMRs).

The primary outcome of this study was defined as response to acalabrutinib (clinical complete remission, complete response, partial response, or partial response with lymphocytosis) at 3 months after the initiation of therapy +/- 1 month) in CLL in patients with concomitant PPI therapy vs no concomitant PPI therapy.⁶

It was anticipated that not all patients would have restaging bone marrow biopsies or imaging completed at 3 months. Therefore, patients meeting clinical and laboratory complete remission criteria were considered to have achieved a clinical complete remission. Participants were considered to have taken concomitant therapy if they had documented evidence of taking a PPI while on acalabrutinib for a minimum of 1 day.

Statistical Analysis

Descriptive statistics were used to report baseline demographics and the number of patients with clinical complete remission, complete response, partial response, partial response with lymphocytosis, and stable disease. Response rates were summarized as a percentage of the number of patients per clinical response group over the total number of patients taking acalabrutinib therapy. Fisher’s exact test was used to compare responses between patients ever taking concomitant acalabrutinib and PPI therapy throughout the study period vs those never taking concomitant therapy.

Results

A total of 65 participants met inclusion criteria. The median duration of follow up was 12 months (range 3.2-26.9 months). Baseline demographics and disease characteristics were similar to those living with CLL in the general population (Online Table 1).^1-3

Prior to starting acalabrutinib, 23 of 65 (35.4%) patients were taking a PPI. At the start of acalabrutinib, 4 patients remained on a PPI and 19 (83%) were taken off PPI therapy (18 patients switched to alternative acid suppression therapy and 1 successfully discontinued all acid suppression therapy). When the response rate was assessed at 3 months, 7 patients were taking concomitant PPI therapy (as 3 patients resumed).

Fifty-five patients were included in the response assessment at 3 months. Of 7 patients taking a PPI, 57% had a complete clinical remission and 43% had a partial response with or without lymphocytosis. Of the 48 patients not taking a PPI, 25% had a complete clinical remission and 69% had a partial response with or without lymphocytosis (Online Table 2).^1-3 There was no evidence of a significant association of PPI status, with best response at 3 months post acalabrutinib initiation (P = .59).

Discussion

The results of this study did not support a statistically significant difference in the clinical impact of concomitant acalabrutinib and PPI therapy based on response rates between groups (Online Table 21-3; P = .59). However, the results did highlight the critical role the clinical pharma-cists have in identifying drug interactions prior to initiating a medication. Acid suppression therapy is available for patients to purchase OTC. Therefore, it does not always appear on a patient’s documented medication list within the EMR.

Clinical pharmacists at the University of Rochester Specialty Pharmacy involved in the management of acalabrutinib complete a thorough counseling session with medication reconciliation prior to the initiation of acalabrutinib. In total, 19 of 23 (83%) patients who were taking a PPI prior to the start of acalabrutinib were switched to alternative antacid therapy to avoid this significant drug interaction.

This high substitution rate can be attributed to a highly integrated clinical pharmacist having a discussion with the patient prior to the initiation of acalabrutinib. The clinical pharmacists at the University of Rochester Specialty Pharmacy use a thorough documentation process via an integrated flow sheet within the EMR.

It was confirmed via this documentation that discussions with providers regarding the interaction did occur for the remaining 4 of 23 patients. These patients were not ultimately considered to be candidates for a switch in therapy because of either failing with a previous switch attempt or having a separate diagnosis that requires PPI therapy.

There were several limitations to this study. First, there was a small sample size exposed to concomitant therapy, as just 7 patients had been on both acalabrutinib and a PPI at least once when the primary outcome was measured at 3 months post acalabrutinib initiation. A larger sample size with more concomitant use of acalabrutinib and a PPI would allow for further evaluation of the clinical impact of this interaction.

Additionally, this study was completed over a time period affected by the COVID-19 pandemic, when telemedicine visits frequently replaced in-person office visits. Therefore, patients with telemedicine visits at 3 months lacked objective laboratory and physical assessments to verify clinical response.

Finally, a large number of patients were taking additional therapies other than acalabrutinib to target their disease state, which could have affected response rates. Additionally, all had differing disease features, which put some at a higher risk than others for disease progression. Although these confounders may have affected response rates, the heterogeneity in the patient population included in this study is representative of the real-world population seen in clinical practice.

Conclusion

The high rate of acid suppression therapy substitution noted in this study highlights 1 benefit of the integrated HSSP model. These observations suggest specialty pharmacists’ continuous assessment, ongoing monitoring, and counseling services lead to mitigation of drug interactions and optimization of drug therapy in this patient population.

Given the large switch rate (83%) at baseline from a PPI to a different antacid therapy that was observed within this study, there were minimal data for patients who were concomitantly administering acalabrutinib and PPI therapy. Throughout the entire duration of follow-up, 84% of patients were able to remain off PPI therapy. Further investigation with a clinical trial that has a larger patient population taking concomitant acalabrutinib and PPI therapy is required to determine the impact of this interaction on clinical practice.

References

1. Ghia P, Pluta A, Wach M, et al. ASCEND: phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2020;38(25):2849-2861. doi:10.1200/jco.19.03355

2. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667. doi:10.1016/S0140-6736(17)33108-2

3. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395 (10232):1278-1291. doi:10.1016/S0140-6736(20)30262-2

4. Calquence. Prescribing information. AstraZeneca; 2017. Accessed August 8, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/210259s000lbl.pdf

5. A study of acalabrutinib vs investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab in R/R CLL. ClinicalTrials.gov. Updated June 23, 2022. Accessed August 8, 2022. https://clinicaltrials.gov/ct2/show/NCT02970318

6. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-2760. doi:10.1182/blood-2017-09-806398