Ibrutinib for mantle cell lymphoma at first relapse: a United Kingdom real‐world analysis of outcomes in 211 patients

Abstract

Ibrutinib is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL) and clinical trial data supports use at second line compared to later relapse. We aimed to investigate outcomes and tolerability for ibrutinib when given second line in a real-world setting. Our multicentre retrospective analysis included 211 R/R MCL patients, median age 73 years, receiving ibrutinib second-line within the United Kingdom's National Health Service. Overall response to ibrutinib was 69% (complete response 27%). The median progression-free survival (PFS) was 17Á8 months (95% CI 13Á1-22Á2) and median overall survival (OS) 23Á9 months (95% CI 15Á0-32Á8). Drug-related adverse event led to dose reduction in 10% of patients and discontinuation in 5%. In patients with progressive disease, accounting for 100 of 152 patients stopping ibrutinib, 43% received further systemic therapy. Post-ibrutinib rituximab, bendamustine and cytarabine (R-BAC) showed a trend toward improved survival compared to alternative systemic treatments (post-ibrutinib median OS 14Á0 months, 95% CI 8Á1-19Á8, vs. 3Á6 months, 95% CI 2Á6-4Á5, P = 0Á06). Our study confirms the clinical benefit and good tolerability of ibrutinib at first relapse in a real-world population. Patients progressing on ibrutinib had limited survival but outcomes with R-BAC in select patients were promising.

Impact of Mantle Cell Lymphoma Contamination of Autologous Stem Cell Grafts on Outcome after High-Dose Chemotherapy

“…Identifying MCL patients at increased risk for relapse after HDCT/Auto-HSCT is of growing importance as novel therapeutic options, including bruton tyrosine kinase (BTK) inhibitors, immunomodulatory agents and chimeric antigen receptor (CAR) T cell therapies have improved the prognosis of MCL patients relapsing after HDCT/Auto-HSCT and might even challenge the status of HDCT as standard frontline treatment in the future [ 33 , 34 , 35 , 36 , 41 ]. Furthermore, at-risk patients might benefit particularly from maintenance therapy after Auto-HSCT, the significance of which remains unsettled in the context of different induction therapy regimens [ 1 , 30 , 31 , 32 ].…”

“…As such and due to its association with early relapse, detection of graft-MRD raises the question whether HDCT/Auto-HSCT remains the adequate treatment strategy in these poor-responding patients. Both BTK inhibitor-based and CAR T cell therapy, despite a lack of data in this setting, here represents promising and legitimate alternatives [ 35 , 36 , 41 ]. While future studies need to define the role of BTK inhibitors and CAR T cell therapy in patients not achieving a CR after induction chemoimmunotherapy, positive graft-MRD already advocates for maintenance therapy and close follow-up disease monitoring after Auto-HSCT.…”

“…Thus, only the mantle cell lymphoma international prognostic index (MIPI) [ 21 , 22 , 23 , 24 ] and post-induction response assessment with computed tomography (CT) are routinely available to identify patients at increased risk for relapse. This is critical considering the growing importance of risk stratification in MCL as (i) the role of maintenance therapy after Auto-HSCT, despite its recommendation by various guidelines [ 1 , 25 , 26 ], in clinical practice remains unsettled as its benefit is likely to depend on the treatment regimen used for induction and rituximab maintenance is yet to receive formal approval in many countries [ 1 , 27 , 28 , 29 , 30 , 31 , 32 ] and (ii) novel therapeutic options have improved the prognosis of MCL patients relapsing after Auto-HSCT in recent years [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ] and might even challenge the status of HDCT/Auto-HSCT in the future.…”

NCCN Guidelines® Insights: B-Cell Lymphomas, Version 5.2021

“…Limited data from retrospective studies suggest that venetoclax monotherapy and the RBAC regimen result in favorable response rates in patients with R/R MCL after BTK inhibitor therapy. 43,[51][52][53] However, the optimal second-line therapy for management of R/R MCL after BTK inhibitor therapy has not been established in prospective studies. 48,54,55 Allogeneic HCT is a potentially curative option for eligible patients with R/R disease that is in remission following second-line therapy.…”

How should we use ibrutinib in patients with mantle cell lymphoma?

“…10 In a series of pooled data from clinical trials, it was noted that outcome with ibrutinib is superior when used as secondline treatment, compared to later lines, associated with a median PFS of 25 vs 10 months, indicating that earlier use may be of benefit. 11 In a recent issue of BJHaem, McCulloch et al, 12 report a multicentre retrospective analysis of 211 MCL patients from the UK, investigating the approach of giving ibrutinib as second-line therapy. Although not all patients could be included nation-wide, these data should provide a more realistic picture of efficacy and safety outside of the clinical trial situation.…”