Cytarabine-based induction immunochemotherapy in the front-line treatment of older patients with mantle cell lymphoma

Abstract

The role of cytarabine-based induction and autologous stem cell transplantation (ASCT) in front-line treatment of younger patients with mantle cell lymphoma (MCL) is well established, however the utility of intensive approaches in older patients remains unclear. This retrospective study compared first line treatment outcomes in patients aged 60 years or more, treated at six tertiary centres between 2000–2015. 70 patients included had a median age of 69 (60–91) and most (94%) demonstrated advanced stage disease. Treatment regimens included: R-CHOP-like (n = 39), alternating R-CHOP/R-DHAC (n = 10), R-HyperCVAD/R-MA (n = 7), R-CHOP/Cytarabine (Nordic Protocol) (n = 10) and other (n = 4). 16 patients underwent an ASCT. The median follow-up for surviving patients was 37 months. Compared to R-CHOP-like therapies, cytarabine-based regimens were associated with an improved overall response rate (ORR) of 70% vs 33% (p < 0.001) and overall survival (OS) (HR 0.541, [0.292–1.001], p = 0.05). No difference in efficacy between different cytarabine-based regimens was detected, but R-HyperCVAD/R-MA was associated with increased hospitalisation and transfusion requirements. Patients undergoing ASCT demonstrated an improved median OS (HR 0.108 [0.015–0.796], p = 0.029) but were significantly younger. These results reaffirm the use of cytarabine in MCL for selected patients aged over 60. Such regimens should be strongly considered for this population in frontline therapy.

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

“…[65] as compared with other studies which found that severe AEs in elderly/unfit patients with MCL occur in < 5% of patients [2,61]. The reasons for this discrepancy are unclear but highlight the importance of comparing data from different sources.…”

“…Following removal of duplicate papers, 901 papers remained; of these 805 articles were removed after the titles and abstracts were screened, leaving 66 articles for full screening. From these papers, 16 articles met all the inclusion criteria, and were taken forward for qualitative synthesis ( Table 2 [ 13 , 23 , 24 , 32 , 54 , 55 , 56 , 57 , 58 , 59 – 61 , 63 , 64 , 65 , 67 ]).…”

Consenso del Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL) para el manejo del Linfoma en estado de Pandemia SARS CoV-2 / COVID 19

“…Las guías internacionales como por ejemplo las de NCCN recomiendan una vez tomada la decisión de tratar, los protocolos intensivos solamente para los estadios II con masa bultosa, Estadios III o IV que tengan comportamiento agresivo, incluyendo aquellos con mutación TP53 y que sean candidatos a trasplante 136 . Sin embargo, estos regímenes intensivos de quimioterapia se acompañan de un perfil de toxicidad significativo relacionado con el tratamiento, incluyendo linfopenia (88%), trombocitopenia (85%), neutropenia (83%), neutropenia febril (15%), mucositis e infecciones graves, diarrea, náuseas, emesis y eritemas cutáneos; contraproducentes todos en este contexto de la pandemia por COVID-19, si las Instituciones no pueden garantizar acortar las estancias hospitalarias de estos esquemas y tomar todas las medidas necesarias para disminuir el riesgo de contagio por coronavirus [158][159][160] .…”

“…Los esquemas con dosis altas de citarabina resultan ser suficientemente eficaces en términos de sobrevida libre de progresión y sobrevida global para evitar el TAPH, por ende, si el tratamiento ya está iniciado, sería mejor no suspenderlo o modificarlo [158][159][160] .…”

Genetic heterogeneity and prognostic impact of recurrent ANK2 and TP53 mutations in mantle cell lymphoma: a multi-centre cohort study

“…However, the pathogenesis of MCL is complex and the alterations in the genes involved in DNA damage response (ataxia telangiectasia mutated [ATM], checkpoint kinase 2 [CHK2], and TP53) and cell survival signalling pathways (Bruton's tyrosine kinase [BTK], mammalian target of rapamycin [mTOR], nuclear factor-κB [NF-κB], tumour necrosis factor [TNF], and NOTCH) also play crucial roles 5 . Moreover, MCL patients exhibit diverse responses to therapies and clinical courses 6,7 , which has not been completely incorporated by current risk stratification tools. Therefore, it is essential to investigate the genetic landscape of this heterogeneous disease to gain insight into the molecular pathogenesis and to predict the prognosis of MCL patients.…”