Prognostic Significance of Clinical Characteristics and Baseline PET-CT Metabolic Parameters in Patients with Marginal Zone Lymphoma
Authors: Nizamuddin Imran A. , Haq Adeel , Wan Fei , Watkins Marcus P. , Shea Lauren Kelly , Bartlett Nancy L. , Kahl Brad S. , Mhlanga Joyce , Mehta-Shah Neha 
Published: December 2024

Background: While marginal zone lymphoma (MZL) is generally an indolent non-Hodgkin lymphoma, some patients (pts) have a more aggressive course. The prognostic role of positron emission tomography (PET)-computed tomography (CT) imaging is not well-characterized in MZL. We sought to investigate the prognostic impact of SUVmax in pts with newly diagnosed MZL.

Methods: We conducted a single-center retrospective cohort study of adults with biopsy-proven MZL without transformation diagnosed from 1/1/2010-3/1/2023. Demographics, clinical, and treatment data were collected. Metabolic parameters on baseline PET-CT including SUVmax and SUVmean of lymphomatous lesions and background hepatic and blood pool activity were independently calculated using standard methods on MIM and Hermes viewer. An optimal cut-off for a binary SUVmax variable (high vs low) was determined using a minimal p-value approach based on log-rank test statistics. Kaplan-Meier method and log-rank test was used to compare differences in progression-free survival (PFS) and overall survival (OS) between high and low SUVmax groups among each subtype. Corresponding Cox proportional hazards models were fitted to estimate hazard ratios.

Results: Of 183 pts with MZL, 40.4% were male with median age at diagnosis of 64 (range: 29-90). Majority had extranodal MZL (ENMZL, n=101, 55.2%), followed by nodal MZL (NMZL, n=49, 26.8%) and splenic MZL (SMZL, n=33, 18.0%). There was no significant difference in age, gender, B symptoms at diagnosis, baseline LDH, rates of frontline observation, or rates of progression between subtypes. Seven (3.8%) pts later experienced disease transformation (4 ENMZL, 3 NMZL).

Forty-two pts (23%) were observed as initial treatment for median of 44 months, and 16 pts later progressed requiring treatment after a median of 18 months. Advanced stage (p=0.009), multiple extranodal sites (p&lt;0.001), and NMZL (p=0.05) were most predictive of requiring treatment after observation. Most common treatments were radiation (n=60, 32.8%), bendamustine with rituximab (BR) (n=45, 24.6%), and rituximab monotherapy (R) (n=31, 16.9%). Forty-three pts (23.5%) progressed requiring second-line treatment. Response rates for R, BR, and radiation were 64.5%, 82.2%, and 90%, respectively. Pts with extranodal sites (p&lt;0.001) were more likely to progress after initial treatment. Those treated with R were more likely to progress than those treated with other regimens (p=0.008).

Overall, 5-year PFS was 79.4% and 5-year OS was 90.0%. When comparing subtypes, 5-year PFS for ENMZL, NMZL, and SMZL were 80.1%, 78.4%, and 79.9%, respectively. There was no significant difference in PFS or OS based on subtype of MZL.

SUVmax was reliably measured for 128 pts (72 ENMZL, 39 NMZL, 17 SMZL), with median 6.1 (range: 1.4-31.8). Optimal SUVmax cutoff was found to be 8.4. PFS and OS were both significantly worse in pts with SUVmax ≥8.4 (5-year PFS 82.9% vs 69.8%, HR 2.06, p=0.0398; 5-year OS 93.8% vs 82.2%, HR 3.11, p=0.0133). SUVmax cutoff of 8.4 was most predictive of PFS and OS in ENMZL (5-year PFS 87.9% vs 55.6%, HR 3.71, p=0.0059; 5-year OS 92.1% vs 84.6%, HR 3.02, p=0.0683). It was also predictive of PFS and OS in NMZL (5-year PFS 83.6% vs 75.4%, HR 1.69, p=0.390; 5-year OS 94.7% vs 75.3%, HR 2.27, p=0.343). Only 5 pts (29.4%) with SMZL had SUVmax ≥8.4 and 5-year OS was 100% in this group. Excluding pts initially observed, cutoff SUVmax ≥8.4 remained significantly associated with inferior OS (5-year OS 93.5% vs 82.6%; HR 3.40, p=0.0163), but not PFS (5-year PFS 82.6% vs 71.2%; HR 1.58, p=0.2683). SUVmax cutoff of 8.4 remained most predictive of PFS and OS in ENMZL (5-year PFS 85.0% vs 47.6%, HR 2.84, p=0.0379; 5-year OS 90.4% vs 81.7%, HR 2.86, p=0.0837) and NMZL (5-year PFS 90.0% vs 86.5%, HR 1.43, p=0.7022; 5-year OS 100% vs 78.1%, HR 2.38, p=0.4544).

Conclusions: While treatments for MZL remain very effective with high response rates leading to prolonged progression-free survival across disease subtypes, patients with ENMZL and NMZL with SUVmax &gt;8.4 demonstrate inferior PFS and OS. The predictive value of SUVmax was seen in the entire cohort as well as when excluding those who were initially observed. Conclusions for SMZL were limited by sample size and overall low FDG avidity.