Early progression as a predictor of survival in marginal zone lymphomas: an analysis from the FIL-NF10 study

Abstract

Marginal zone lymphomas (MZLs) are indolent nonfollicular B-cell lymphomas (INFLs) and have heterogeneous clinical behavior. Recently, time to progression of disease at 24 months (POD24) was identified to stratify overall survival (OS) in follicular non-Hodgkin lymphoma and in INFL. Here, we examined the ability of POD24 to predict subsequent OS in a large, international cohort of MZL as part of the NF10 prospective international registry headed by Fondazione Italiana Linfomi (FIL). POD24 was only calculated for MZL patients requiring immediate therapy and was defined as experiencing lymphoma progression within 24 months from diagnosis. Among the 1325 patients enrolled in the NF10 study, we identified 321 patients with MZL for whom immediate therapy was planned right after lymphoma diagnosis. Overall, POD24 was confirmed in 59 patients (18%). Three-year OS for patients with POD24 was 53% with a hazard ratio of 19.5 (95% confidence interval, 8.4-45) compared with patients without POD24 (3-year OS, 95%). Association of POD24 with OS was confirmed for the subgroup of splenic and extranodal MZLs. Assessment of POD24 stratifies subsequent outcome in MZL and identifies a high-risk population. This trial was registered at www.clinicaltrials.gov as #NCT02904577.

Progression-free survival at 24 months and subsequent survival of patients with extranodal NK/T-cell lymphoma: a China Lymphoma Collaborative Group (CLCG) study

“…Previous studies, mainly using the randomized controlled trial (RCT) or real-world data, have demonstrated that the surrogate endpoints of EFS and PFS are strongly related to OS at both trial- and individual-level in different lymphoma subtypes [ 26 – 29 , 32 , 39 – 41 ]. Consistent with the present finding, the subsequent survival of patients with DLBCL or PTCL who achieved EFS24 or PFS24 is almost equal to that of the age-, sex-, and country-matched general population [ 26 – 29 , 32 ].…”

“…Furthermore, we have confirmed the association of PFS24 with OS in trial- and treatment arm-level in RCTs on DLBCL patients treated with immunochemotherapy; its association has been externally validated using the literature-based data from high-quality phase II and retrospective studies [ 40 ]. Similarly, in patients with follicular lymphoma and marginal zone lymphomas [ 39 , 41 ], early progression of disease within 24 months after initial treatment stratified subsequent OS and identifies a high-risk population. Consistent with the present study, these findings highlight the important role of PFS or EFS as early efficacy endpoint in designing prospective trials.…”

Outcome of relapsed and refractory nodular lymphocyte‐predominant Hodgkin lymphoma: a North American analysis

“…POD24 has been identified as a surrogate marker of OS in patients with indolent B-cell lymphoma, including follicular lymphoma and marginal-zone lymphoma, although these studies evaluated all patients from the time of diagnosis and not just relapsed patients. [26][27][28] While we excluded patients with known transformation at first relapse/progression, we cannot exclude that they may have harboured aggressive lymphoma. However, it is important to note that in our study POD24 did not help identifying patients at higher risk of transformation.…”

Undetectable minimal residual disease is an independent prognostic factor in splenic marginal zone lymphoma

“…MRD detection for those PR patients has a more important value, and we should enhance the follow-up within this special group of patients. Third, as POD24 plays a more important role in predicting adverse prognosis in indolent lymphomas, including marginal zone lymphoma, 10,18,19 how to identify these high-risk patients earlier has become an urgent issue to solve. Our present study demonstrated that MRD positivity after therapy was a powerful indicator, with almost one-third of MRD-positive patients relapsing within 24 months, providing a strong clue for identifying these high-risk POD24 patients.…”