SOHO State of the Art Updates and Next Questions: Managing Relapsed Mantle Cell Lymphoma

Real-World Evidence of Relapsed/Refractory Mantle Cell Lymphoma Patients and Treatments: A Systematic Review

“… 49–51 CAR-T regimen studies did not report median PFS and OS due to their short follow-up, but the longest follow-up by Iacoboni et al 36 reported an estimated 50.8% PFS and 61.4% OS at 12 months, very promising results in this heavily pretreated high-risk patient population. In this context, it is important to note that multivariate analysis have shown several prognostic markers to have a deleterious effect in PFS and OS besides previous lines of therapy in the context of R/R MCL and need to be considered when comparing the efficacy results reported in the different studies: 6 ECOG, sMIPI, bulky disease, early progression of disease (POD24 status), and ultra-high-risk features, such as blastoid/pleomorphic histology and TP53 mutation.…”

“… 59 Additionally, studies using CAR T-cell therapy 61 and bendamustine 47 reported the highest CR rates, whereas the lowest CR values were those reported in clinical trials using bortezomib 59 and lenalidomide. 63 Conversely, the highest median PFS values corresponded to ibrutinib-based therapies 6 , 53 , 55 and CAR T-cell therapies, considering that CAR T-cell therapies have been tried mostly in a post iBTK setting, whereas bortezomib, 59 , 60 together with lenalidomide, 63 yielded the lowest median PFS values.…”

“…Despite recent advances that have prolonged survival, R/R MCL is clinically and biologically heterogeneous and is still a therapeutic challenge, with high-risk and early relapsed patients remaining an unmet medical need. There is no standard treatment for R/R MCL, but considering patients’ advanced age, tolerability profile, and convenient administration, BTKis should be positioned as second line of therapy, 6 and CAR T-cells should be the approach to BTKi-relapsed patients. 61 However, access to CAR T is not universal, and more therapies in this setting are still needed.…”

“… 5 Some clinical and pathological features have been identified as prognostic factors of MCL, such as the MCL International Prognostic Index (MIPI), the Ki-67 index, aberrations in the TP53 tumor suppression gene (eg, TP53 mutations and del17p), presence of blastoid or pleomorphic histologic variants, and an early progression of disease after first-line therapy, especially within the first one or two years. 6 …”

“…5 Some clinical and pathological features have been identified as prognostic factors of MCL, such as the MCL International Prognostic Index (MIPI), the Ki-67 index, aberrations in the TP53 tumor suppression gene (eg, TP53 mutations and del17p), presence of blastoid or pleomorphic histologic variants, and an early progression of disease after first-line therapy, especially within the first one or two years. 6 Historically, several chemotherapy-based strategies have been used for MCL depending on the patient's age, functional status, and number of previous lines of therapy, but most patients eventually relapse. 1 In the last few years, several targeted treatment approaches have been developed for relapsed/refractory MCL (R/R MCL), including Bruton's tyrosine kinase (BTK) inhibitors, B-cell lymphoma 2 (BCL-2) inhibitors, lenalidomide and bortezomib-based approaches, m-TOR inhibitors, and chimeric antigen receptor (CAR) T-cell therapy.…”