Real-World Data Suggest Unmet Need for Effective Post-BTK Inhibitor Options in MCL

Shinya Rai, MD, PhD

For patients with mantle cell lymphoma (MCL) who have progressed after treatment with a BTK inhibitor such as ibrutinib (Imbruvica), there is an unmet need for the development of safe and effective targeted therapies to improve otherwise dismal outcomes, according to data from a retrospective study presented during the 2021 Pan Pacific Lymphoma Conference.

Following completion of treatment with ibrutinib, patients received subsequent therapy that was very diverse. Moreover, after progression on ibrutinib, patients experienced poor outcomes with currently available therapeutic options, with a median time to treatment discontinuation of 1.54 months (95% CI, 1.07-2.00), and a median overall survival (OS) of 5.46 months (95% CI, 3.86-9.39).

“Patients who received post-ibrutinib therapy were in poor health status, experienced frequent adverse effects [AEs], and needed supportive care, indicating high disease and treatment burden,” Shinya Rai, MD, PhD, of Kindai University, and colleagues, wrote.

Currently, no standard-of-care therapies exist for patients with MCL following progression on the BTK inhibitor ibrutinib. As such, investigators sought to gather data on real-world treatment patterns and outcomes for this patient population in Japan.

To this, investigators utilized a hospital-sourced database, Medical Data Vision, which included both inpatient and outpatient claims and discharge information from approximately 25% of acute care hospitals throughout Japan.

To be included in the analysis, patients had to have been diagnosed with MCL between December 2010 to September 2019 (n = 1,914). Among these patients, 1,374 received their first treatment for MCL at the index date and were over the age of 20 years. Moreover, 171 were excluded for receiving other MCL treatments before the index date (n = 170), and for participating in a clinical trial after the index date (n = 1). Overall, 1,203 patients were included in the study, 270 of whom received treatment with ibrutinib.

Any therapies approved in Japan or listed in the Japanese Society of Hematology or National Comprehensive Cancer Network guidelines for MCL were permitted, and regimens defined as MCL drugs were those prescribed within 35 days of the initiation of a specific line of therapy. Additionally, baseline factors were examined within 90 days of treatment initiation, and patients were followed from the index date to the end of available data for their therapies, other cares, and outcomes.

Patients examined on the study had a mean age of 71 years (range, 10-48) and 74.23% were male. Moreover, 10.64% had metastasis, 6.57% of which were bone or bone marrow metastasis. The mean Charlson Comorbidities Index was 2.27 and the mean body mass index was 22.63. Additionally, 86.53% of patients were activities of daily living independent.

Of the 270 patients who received treatment with ibrutinib, 111 (41.1%) received it as a second-line therapy, 58 (21.48%) as a first-line therapy, 57 (21.11%) as a third-line therapy, 27 (10.00%) as a fourth-line therapy, and 17 (6.30%) as a fifth-line or later therapy. Of the 58 patients who received ibrutinib in the frontline, 10 began other therapies on the index date prior to ibrutinib within the 35-day period that defined the first-line regimen.

Moreover, 183 (68%) discontinued ibrutinib and 108 (40%) received subsequent treatment following a BTK inhibitor. Among the 108 patients who received post-ibrutinib therapy, 59% received a unique combination regimen. Of these combinations, 26.85% were bendamustine-based, 18.52% were bortezomib (Velcade)-based, 12.96% were cytarabine-based, and 41.67% were other agents.

The most frequently reported AEs in the ibrutinib therapy arm and the post-ibrutinib therapy arm, respectively, included infection (25.56% vs 26.85%), atrial fibrillation and flutter (9.63% vs 4.63%), gastrointestinal hemorrhage flutter (6.67% vs 4.63%), febrile neutropenia (1.11% vs 12.96%).

The most common methods of supportive care in the ibrutinib and post-ibrutinib arms, respectively, included anti-infectives (32.22% vs 51.85%), arrhythmia procedures (0% vs0.93%), blood transfusions (14.81% vs 38.89%), emergent hospital admission (17.04% vs 5.56%), oral anticoagulants (7.04% vs 3.70%), and radiotherapy (4.07% vs 8.33%).

Limitations to the analysis included partially described or lost treatment information if a patient received treatment at multiple hospitals, incomplete mortality data, and patients may have been misclassified regarding their intended prescribed treatment regimen.

Reference

1. Rai S, Tanizawa Y, Cai Z, et al. Outcomes for recurrent mantle cell lymphoma post-BTK inhibitor therapy in Japan; an administrative database study. Presented at: 2021 Pan Pacific Lymphoma Conference; August 9-13, 2021; Big Island, H