Ibrutinib revolutionized therapy for relapsed/refractory (R/R) mantle cell lymphoma (MCL). Real-world data on the outcome of unselected patients are still limited. We analyzed 77 R/R MCL patients receiving ibrutinib with at least one prior systemic anti-lymphoma therapy. After a median follow-up of 14.0 months, 56 patients relapsed/progressed, and 45 died. The overall response rate was 66%, with 31% of complete metabolic remissions on PET/CT. The median progression-free and overall survival (OS) rates were 10.3 and 23.1 months, respectively. The median OS from ibrutinib failure was 3.7 months. High proliferation rate by Ki67 (≥ 30%) and two or more previous therapy lines both negatively correlated with outcome (HR = 2.2, p = 0.04, and HR = 2.06, p = 0.08, respectively). Female gender borderline correlated with better outcome (HR = 0.53, p = 0.08). In multivariate analysis, 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. From 20 patients with detectable BM infiltration (before ibrutinib initiation) achieving complete (n = 13) or partial (n = 7) metabolic remission, none achieved remission in BM. We confirmed good efficacy of ibrutinib in unselected heavily pre-treated MCL patients. Our findings support the use of a combination of ibrutinib and rituximab in patients with BM involvement.

• Keywords
• Bone marrow, Bruton tyrosine kinase, Chemoresistance, Ibrutinib, Mantle cell lymphoma,
• MeSH
• Ki-67 Antigen MeSH
• Adult MeSH
• Humans MeSH
• Lymphoma, Mantle-Cell * pathology   MeSH
• Positron Emission Tomography Computed Tomography MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Ki-67 Antigen MeSH
• ibrutinib MeSH Browser

Twenty percent of patients with high-tumor-burden (HTB) follicular lymphoma (FL) develop progression/relapse of disease (POD) within 24 months of frontline immunochemotherapy. Unfortunately, about 50% of these patients die within 5 years since POD event. Rituximab maintenance was proven to reduce relapse rate in responding FL, but its role on preventing POD was not defined. We analyzed 1360 HTB-FL patients from the Czech Lymphoma Study Group registry treated with frontline rituximab-containing regimen. Of those, 950 cases received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and achieved complete or partial remission: 712 patients received rituximab maintenance (MAINT) and 238 were a historical observational cohort (OBS). We have proposed a modified POD24 (mPOD24) endpoint for the chemosensitive patients calculated from the end-of-induction (EOI). Survival rates since EOI were as follows: 5-year overall survival (OS) 86.2% versus 94.5% in the OBS and MAINT groups, respectively (P < .001) and 5-year progression-free survival 58.5% (OBS) and 75.4% (MAINT) (P < .001). The Cox proportional hazards model showed a decrease in mPOD24 incidence in the MAINT group with the overall hazard rate reduced by 56% (hazard ratio = 0.44; P < .001). The cumulative incidence of mPOD24 was reduced from 24.1% in OBS to 10.1% in MAINT (P < .001). Comparison of non-mPOD24 cases showed OS similar to that in the general population. Rituximab maintenance given after R-CHOP resulted in a 2.4-fold reduction in mPOD24 incidence. Once the non-POD24 status is achieved, FL does not shorten the patients' life expectancy.

• Keywords
• early progression, follicular lymphoma, maintenance, rituximab,
• Publication type
• Journal Article MeSH

Mantle cell lymphoma (MCL) is a heterogeneous malignancy with a broad spectrum of clinical behavior from indolent to highly aggressive cases. Despite the fact that MCL remains in most cases incurable by currently applied immunochemotherapy, our increasing knowledge on the biology of MCL in the last two decades has led to the design, testing, and approval of several innovative agents that dramatically changed the treatment landscape for MCL patients. Most importantly, the implementation of new drugs and novel treatment algorithms into clinical practice has successfully translated into improved outcomes of MCL patients not only in the clinical trials, but also in real life. This review focuses on recent advances in our understanding of the pathogenesis of MCL, and provides a brief survey of currently used treatment options with special focus on mode of action of selected innovative anti-lymphoma molecules. Finally, it outlines future perspectives of patient management with progressive shift from generally applied immunotherapy toward risk-stratified, patient-tailored protocols that would implement innovative agents and/or procedures with the ultimate goal to eradicate the lymphoma and cure the patient.

• Keywords
• B-cell receptor signaling, cell cycle, mantle cell lymphoma,
• MeSH
• Cell Cycle drug effects   genetics   MeSH
• Drug Resistance, Neoplasm MeSH
• Molecular Targeted Therapy * methods   MeSH
• Genetic Variation MeSH
• Clonal Evolution drug effects   genetics   MeSH
• Combined Modality Therapy MeSH
• Humans MeSH
• Lymphoma, Mantle-Cell drug therapy   etiology   metabolism   mortality   MeSH
• Disease Susceptibility MeSH
• Biomarkers, Tumor antagonists & inhibitors   MeSH
• Prognosis MeSH
• Antineoplastic Agents pharmacology   therapeutic use   MeSH
• Receptors, Antigen, B-Cell metabolism   MeSH
• Recurrence MeSH
• Gene Expression Regulation, Neoplastic drug effects   MeSH
• Signal Transduction drug effects   MeSH
• Treatment Outcome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Biomarkers, Tumor MeSH
• Antineoplastic Agents MeSH
• Receptors, Antigen, B-Cell MeSH