Outcomes for Recurrent Mantle Cell Lymphoma Post-Ibrutinib Therapy: A Retrospective Cohort Study from a Japanese Administrative Database

Abstract

Introduction Treatment options in patients with mantle cell lymphoma (MCL) failing ibrutinib are limited, with no standard therapies defined. This study aimed to investigate real-world treatment patterns and outcomes for patients with MCL following ibrutinib. Methods This study utilized a de-identified hospital-based claims database (Medical Data Vision) in Japan. Eligible patients were adults who were diagnosed with MCL and had received antitumor drugs between December 2010 and July 2020. Patients were followed from the first antitumor drug treatment until the end of available data up to July 2021. Time-to-event analyses utilized the Kaplan–Meier method. Factors for receiving post-ibrutinib therapy were explored with logistic regression analysis. Results Of the 1386 patients who started antitumor drug therapy, 247 patients received and discontinued ibrutinib at any line of therapy. Among them, 137 patients (55.5%) received subsequent therapy. The median age at the end of ibrutinib therapy was 77 (range 42–95), and 44 patients had a dependent activity of daily living (ADL). Factors negatively associated with receiving post-ibrutinib therapy after discontinuation of ibrutinib were age ≥ 75 years (odds ratio [95% CI] 0.46 [0.26–0.80]) and emergency hospital admissions (0.37 [0.17–0.84]). Immediate post-ibrutinib therapy regimens were highly diverse, with BR (bendamustine, rituximab) only prescribed in more than 10% of patients. The median duration of post-ibrutinib therapy was 1.5 months (95% CI 1.07–2.07). The median overall survival from the end of ibrutinib therapy in patients regardless of the receipt of post-ibrutinib therapy ( n = 247), in those who did not receive post-ibrutinib therapy ( n = 110), and in those who received post-ibrutinib therapy ( n = 137) was 5.6 months (95% CI 3.8–8.7), 2.3 months (95% CI 1.2–3.9), and 8.7 months (95% CI 5.6–13.8), respectively. The most common adverse event during post-ibrutinib therapy was infection, with the use of anti-infectives (17%). Conclusions Patients with MCL previously treated with ibrutinib have poor ability to carry out ADL and experience very poor outcomes. New safe, effective therapies are needed. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02258-3.

Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma

“…Importantly, the OS observed 12-month survival rate of 68% appears promising, given the reports in similar cohorts from the literature (median survival <10 months). 3,[7][8][9]25 The exact mechanisms by which pirtobrutinib is efficacious in MCL after cBTKi treatment is incompletely understood as BTK mutations are rarely observed in MCL. 4,12,13 Pirtobrutinib has favorable pharmacokinetics with high oral bioavailability and Time Since First Dose (months) a 19-hour half-life, attaining continuous BTK inhibition (>IC90) throughout the dosing interval, regardless of intrinsic rate of BTK turnover.…”

“…months. 3,5,[7][8][9] Recent availability of CD19-targeted chimeric antigen receptor (CAR) T-cell therapy for R/R MCL has expanded treatment options, but access is limited, not all patients qualify, and treatment is associated with severe toxicities. 10 Therefore, there remains a significant unmet medical need for efficacious, broadly accessible, and well-tolerated therapies for patients with MCL after cBTKi treatment.Resistance mechanisms to cBTKi vary by tumor type.…”

Treatment outcomes of mantle cell lymphoma in real-world practice: analysis of forty-one patients

“… 11 Numerous real-world MCL datasets have recently been reported using an administrative database with a large cohort. 12 However, due to the rarity and heterogeneity of MCL, there have not been enough reports about treatment outcomes following recent treatment strategies.…”

Pevonedistat, a Nedd8-activating enzyme inhibitor, in combination with ibrutinib in patients with relapsed/refractory B-cell non-Hodgkin lymphoma

“…However, ibrutinib induces complete responses (CR) in only a fraction of patients [ 14 ]. Furthermore, patients with R/R MCL or CLL who develop ibrutinib resistance are high-risk with poor survival outcomes (median OS of 9.3 months in CLL [ 15 ] and 5.6 months in MCL [ 16 ]). Lastly, ibrutinib demonstrates low efficacy in histologies such as DLBCL and follicular lymphoma (FL).…”