Treatment patterns and outcomes of unfit and elderly patients with Mantle cell lymphoma unfit for standard immunochemotherapy: A UK and Ireland analysis

Abstract

Mantle cell lymphoma (MCL) presenting in elderly, unfit patients represents a clinical challenge. Front-line 'attenuated' or low-intensity immunochemotherapy is often employed, although outcomes are relatively unexplored. We report outcomes of attenuated immunochemotherapy in 95 patients with MCL across 19 centres in the UK and Ireland considered unfit for full-dose rituximab-bendamustine or rituximab-cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP). Regimens examined were rituximab-cyclophosphamide, vincristine, prednisolone (R-CVP) (n = 19), dose-attenuated R-CHOP (n = 22), dose attenuated rituximab-bendamustine (n = 24) and rituximab-chlorambucil (n = 30). The primary outcome was progressionfree survival (PFS). The secondary outcomes included overall response, overall survival (OS) and toxicity. The median (range) age was 79 (58-89) years and 50% were aged ≥80 years. The median (range) Cumulative Illness Rating Scale-Geriatric score was 6 (0-24). The median PFS for all patients was 15 months [95% confidence interval (CI) 8Á7-21Á2) and median OS was 31Á4 months (95% CI 19Á7-43Á2). By multivariable analysis (MVA), the only clinical factor associated with an inferior PFS was blastoid morphology [hazard ratio (HR) 2Á90, P = 0Á01). Notably, higher treatment intensity (R-CHOP/R-bendamustine composite) provided an independently superior PFS compared with R-CVP/R-chlorambucil (MVA HR 0Á49, P = 0Á02). Factors associated with inferior OS by MVA were Eastern Cooperative Oncology Group Performance Status (HR 2Á14, P = 0Á04), blastoid morphology (HR 4Á08, P = 0Á001) and progression of disease at <24 months status (HR 5Á68, P < 0Á001). Overall, survival after front-line dose-attenuated immunochemotherapy is unsatisfactory. Clinical trials investigating novel agents such as Bruton tyrosine kinase and Bcell lymphoma 2 inhibitors in this specific clinical setting are warranted.

Mantle cell lymphoma treatment options for elderly/unfit patients: A systematic review

“…Thus, although the data suggest that BR therapy was not inferior to R‐CHOP, it is important to take into consideration that this may not be the case because of the better demographics of the patients treated with BR. This is in line with a study completed in the United Kingdom after our data collection which found that the PFS of elderly/unfit patients treated in the United Kingdom with BR and R‐CHOP was not significantly different [ 72 ].…”

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

“…In this study, age (≥ 75 years) was a significant risk factor associated with failure of receiving subsequent therapy. Previous studies have reported similar findings [ 38 – 40 ], indicating a lack of effective therapy for this patient population. Other factors indicative of failure to receive post-ibrutinib therapy were emergency hospital admissions and poor ADL during ibrutinib therapy.…”

Real-world treatment and outcome patterns of patients with mantle cell lymphoma in China: a large, multicenter retrospective analysis

“…The standard frontline therapy for MCL is not completely uni ed, however, there is a general consensus that cytarabine-containing chemotherapy combined with autologous hematopoietic stem cell transplantation as the rst-line treatment for young and t patients, whereas older or un t patients are treated with combination chemo-immunotherapy according to different tolerance (9,(20)(21)(22)(23). Although the bene t of high-dose cytarabine is clear, due to different clinical trial results, the recognized uni ed regimen is not de nite.…”