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Marginal zone lymphoma
ongoing TRANSCEND FL study (NCT04245839) patients with relapsed/refractory follicular lymphoma and MZL are being treated with lisocabtagene maraleucel. This and other studies will help to define the role of anti-CD19 CAR T cells in this disease.
Lenalidomide and rituximab is an active combination in patients with MZL. Leonard et al. included 63 patients with relapsed/refractory MZL (18% of the study popula- tion) in the AUGMENT study, in which patients with indolent B-cell lymphoma were randomized to either rit- uximab or rituximab and lenalidomide.94 Overall, the study indicated an improvement in PFS (hazard ratio=0.46) from the addition of lenalidomide although this did not reach statistical significance in the small sub- set of patients with MZL. A phase II trial in treatment- naïve patients resulted in an ORR of 93% (complete responses, 70%).95 In a report of the long term follow-up of the MZL subset of this study, the median PFS was 59.8 months and the 5-year OS was 96%.96
Future directions
The COUP-1 single-arm, phase II study (NCT03474744) is evaluating copanlisib and rituximab combination therapy in treatment-naïve and relapsed MZL patients ineligible for local therapy.22 The German Lymphoma Alliance has also planned the POLE-1 trial (NCT03474744), a single-arm, phase II German and Italian collaborative study designed to evaluate the clini- cal performance of pembrolizumab in treatment-naïve and relapsed-confirmed MZL patients with nodal, extran- odal, or splenic disease who are ineligible for local thera- py. The German Lymphoma Alliance’s OLYMP-1 trial (NCT03322865) is a single-arm phase II study that is designed to evaluate the clinical performance of obinu- tuzumab as a single agent in treatment-naïve MZL patients with nodal, extranodal, or splenic disease who are ineligible for local therapy. The IELSG38 study (NCT018085990), which investigated chlorambucil in combination with subcutaneous rituximab in patients with MALT lymphoma, has completed its enrollment phase, and follow-up and analysis is now ongoing. The IELSG48 randomized phase III study is planned to com- pare the clinical performance of rituximab single-agent therapy with that of rituximab combined with acalabru- tinib in patients with splenic MZL in the first-line setting. The IELSG49 study (NCT04646395) is a run-in pilot study of tafasitamab (an anti-CD19 antibody) in combi- nation with acalabrutinib in patients with relapsed or refractory MZL in whom previous systemic therapy has failed. The ongoing MALIBU-IELSG47 study
(NCT03697512) is evaluating ibrutinib plus rituximab combination therapy in untreated MZL, including extra- nodal MZL, splenic MZL, and nodal MZL. The primary endpoints of the MALIBU study are complete response at 12 months and progression-free survival at 5 years.
Conclusions
MZL are a group of indolent B-cell lymphomas with considerable heterogeneity in terms of clinical presenta- tion, biology, etiology and therapeutic approaches. Most patients with limited stage MALT lymphoma have an excellent prognosis with either antibiotics (H. pylori-asso- ciated gastric MALT) or radiotherapy (gastric and non- gastric sites). In the absence of symptoms, splenic MZL can be observed, while symptomatic patients can be managed with rituximab monotherapy or eventually splenectomy or chemo-immunotherapy if needed. Patients with nodal MZL can be managed in a similar fashion to those with follicular lymphoma. Histological transformation is rare but associated with inferior out- comes and should be managed with anthracycline-based chemo-immunotherapy. Newer targeted agents including BTK inhibitors, PI3K inhibitors, and immunomodulatory drugs are active in patients with relapsed/refractory dis- ease. At present, the role of CAR T-cell therapy in MZL is under investigation in several trials. Future studies will define more active novel combinations.
Disclosures
CYC has received fees for consulting and advisory services and honoraria from Roche, Janssen, MSD, Gilead, Ascentage Pharma, AstraZenecca, Lilly, TG therapeutics, Beigene, Novartis, and BMS; research funding from BMS, Roche, Abbvie; and travel expenses from Roche. TMH has participated in data monitoring committees for Seagen and Tess Therapeutics, has sat on scientific advisory boards for Eli Lilly & Co., Morphosys, Incyte, Biegene, and Loxo Oncology; he receives no personal compensation for these activities. His insti- tution receives the compensation. DR receives no personal com- pensation. His institution has received honoraria from AbbVie, AstraZeneca, and Janssen; and research grants from AbbVie, AstraZeneca, and Janssen. EZ’s institution has received research support from AstraZeneca, Celgene, Incyte, Janssen, Merck, and Roche; honoraria for advisory boards services from Beigene, Celgene, Incyte Janssen, Merck, Roche, Celltion Healthcare, and Kyte (a Gilead Company); and travel grants from Abbvie and Roche.
Contributions
All authors revised and approved the manuscript.
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