Real-world data show effective outcomes following ibrutinib and rituximab treatment in patients with relapsed/refractory mantle cell lymphoma with bone marrow involvement.
The use of ibrutinib (Imbruvica) and rituximab (Rituxan) in heavily pre-treated patients with relapsed/refractory mantle cell lymphoma (MCL) who have bone marrow involvement is supported by findings from a real-world study.
In a population of 77 patients and after a median follow-up of 14 months, 56 relapsed or progressed and 45 died. The overall response rate was 66% in patients treated with the ibrutinib and rituximab combination, of whom, 31% had metabolic complete responses (CRs). Moreover, the median progression-free survival was 10.3 months (95% CI, 1.2-66.0) and median overall survival (OS) was 23.1 months (95% CI, 1.2-82.5).
In particular, patients who responded to ibrutinib and rituximab treatment had a median OS of 28.8 months (95% CI, 24.2-45.2) vs 8.3 months (95% CI, 4.3-11.2) for non-responders (P = .005). Moreover, the median OS was not reached in patients who did not relapse and 12.6 months (95% CI, 8.7-24.2) in those who did.
The trial was conducted in a Czech patient population and was part of the Observational Epidemiology and Clinical Study (NCT03199066). MCL diagnoses were reviewed by local hematopathologists by 2016 World Health Organization classification.
To be included in the study, patients needed to be 18 years of age or older with an ECOG performance status of 0 to 2. Additional inclusion criteria included receiving at least 1 previous systemic anti-lymphoma therapy, receiving ibrutinib for at least 1 day, and commencement by July 2020. Of the patients who enrolled, 11 were treated as part of the phase 3 RAY (NCT01646021) and SYMPATICO (NCT03112174) trials.
Patients received trephine biopsy and bone marrow aspiration at the time of starting treatment with ibrutinib. The marrow was then assessed by immunohistochemistry and/or fluorescence-activated cell sorting. Moreover, patients were diagnosed with MCL from November 1997 to December 2019.
The median patient age at diagnosis was 68 years (range, 42-82) and the median age at the start of treatment with ibrutinib was 70 years. In total, 78% of patients were men. All patients with the exception of 2 received a rituximab-based regimen, and the median number of prior lines of therapy before ibrutinib was 2 (range, 1-8).
A total of 20 patients with bone marrow involvement achieved a response, 13 of whom had a CR and 7 had a partial response. Although no patients with bone marrow involvement experienced MCL remission, 30% had a reduction in MCL load in bone marrow, 35% had stable bone marrow involvement, and 35% had a significant increase in bone marrow load. Two patients who did not have bone marrow involvement prior to ibrutinib treatment had isolated bone marrow progression.
Findings from the univariate and multivariate analyses indicated that progression of diseases prognostic indexes at diagnosis were negatively associated with OS (HR, 2.99; 95% CI, 2.08-2.87; P <.05) but did not correlate with OS after the start of ibrutinib treatment. Moreover, a high Ki67 proliferation was associated with a shorter OS (HR, 2.20; P = .04). OS was significantly longer in those who received 1 prior line of therapy at 36.1 months (95% CI, 32.3-52.5) vs those treated with 2 or more lines of treatment at 12.6 months (95% CI, 8.7-24.2; P = .03).
Obr A, Benesova K, Janikova A, et al. Ibrutinib in mantle cell lymphoma: a real-world retrospective multi-center analysis of 77 patients treated in the Czech Republic. Ann Hematol. Published online November 11, 2022. doi:10.1007/s00277-022-05023-2