Ibrutinib Demonstrated Efficacy Among Patients With Heavily Pretreated R/R MCL

Results from a Real-World Retrospective Multicenter Analysis

Ibrutinib demonstrated good efficacy in unselected heavily pre-treated mantle cell lymphoma (MCL) patients, according to a retrospective real-world multicenter analysis published in Annals of Hematology. The study findings additionally support the continued use of a combination therapy of ibrutinib and rituximab for patients with MCL with bone marrow involvement.

"Ibrutinib revolutionized therapy for relapsed/refractory (R/R) mantle cell lymphoma," wrote Ales Obr, MD, Palacky University and University Hospital, Olomouc, Czech Republic, and coauthors. They stated that although previous studies have found that “ibrutinib offers an ideal treatment option for heavily pre-treated MCL patients, [...] real-world data on unselected patients are still insufficient.” 

In order to expand the knowledge on ibrutinib treatment in a real-world setting, study authors aimed to assess endpoints including overall response rate, complete metabolic remissions on positron emission tomography/computed tomography (PET/CT), progression-free survival, overall survival, and safety. 

77 patients with R/R MCL who had received ibrutinib as salvage therapy after ≥ 1 prior systemic anti-lymphoma treatment were enrolled in this study. All patients were recruited from Czech university centers and were diagnosed with MCL between November 1997 and December 2019. Patients had received a median of 2 lines of treatment before ibrutinib treatment.

At the median follow-up date of 14 months, the overall response rate was 66%, with 31% of complete metabolic remissions on PET/CT. At the median followup of 14 months, 56 patients relapsed or progressed, and 45 died. The median progression-free survival was 10.3 months, and the median overall survival was 23.1 months. The median overall survival (OS) from ibrutinib failure was 3.7 months. Study authors found that high proliferation rate by Ki67 (≥ 30%) and 2 or more previous therapy lines both negatively correlated with outcome (HR = 2.2, p = 0.04, and HR = 2.06, p = 0.08, respectively).

They noted that the female gender borderline correlated with stronger outcomes (HR = 0.53, p = 0.08). In multivariate analysis, nuclear antigen Ki67 and response to ibrutinib both correlated with OS (p < 0.05). Importantly, ibrutinib appeared to better control nodal and extranodal lymphoma than bone marrow (BM) involvement. Notably, from 20 patients with detectable BM infiltration before ibrutinib initiation who achieved complete (n = 13) or partial (n = 7) metabolic remission, none achieved remission in BM.

“We confirmed good efficacy of ibrutinib in unselected heavily pretreated MCL patients,” study authors concluded. “Our findings support the use of a combination of ibrutinib and rituximab in patients with [bone marrow] (BM) involvement."

They added, “Data on ibrutinib efficacy in unselected patients with R/R MCL outside prospective clinical trials are still limited,” and more research will be necessary for expansion. 

Source: 

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. 102, 107–115 (2023). https://doi.org/10.1007/s00277-022-05023-2