AUTHORS
Georgios N. Pongas, M.D., Prokop Vodicka, MD, PhD2, Pavel Klener, MD, PhD, Prof.3, David Salek, MD4, Alice Sykorova, MD, PhD5, Heidi Mocikova, MD, PhD6, Vit Karel Prochazka, MD, PhD, Prof.7, Juraj Duras, MD8, Jan Pirnos, MD9, Katerina Steinerova, MD10, Michal Masar, MD11, Andrea Janikova, MD, PhD, Assoc. Prof.12, Josef Karban, MD, CSc13, David Belada, MD, PhD14, Jozef Michalka, MD15, Pavla Stepankova, MD16, Frantisek Folber, MD, PhD17, Jitka Dlouha, DiS18, Petra Blahovcova, MS19, Zuzana Prouzova, MD20, Jan Galko, MD21, Vit Campr, MD22, Juan Pablo Alderuccio, MD23, Magdalena Klanova, MD, PhD24, Dominic Earl Mitchell Jarrett, MD25, Wei Zhao26, Jennifer Chapman, MD27, Isildinha Reis, PhD28, Marek Trnený, MD, CSc, Prof.29, Izidore S. S. Lossos, M.D.30
AFFILIATIONS
1 Sylvester Comprehensive Cancer Center, Miller School of Medicine, Miami, Florida, United States
2 First Department of Medicine, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic
3 First Department of Medicine, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic
4 Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University and University Hospital, Brno, Czech Republic
5 Fourth Department of Internal Medicine – Hematology, Faculty of Medicine, Charles University and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
6 Department of Hematology, Fakultni nemocnice Kralovske Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czech Republic
7 Department of Haemato-Oncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czech Republic
8 Department of Hematology, Medical Faculty of the Ostrava University and University Hospital, Ostrava, Czech Republic
9 Hospital Ceské Budejovice, Department of Oncology, Ceské Budejovice, Czech Republic
10 Department of Haematology and Oncology, Faculty of Medicine, Charles University and University Hospital Pilsen, Pilsen, Czech Republic
11 First Department of Medicine, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic
12 Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University and University Hospital, Brno, Czech Republic
13 First Department of Medicine, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic
14 Fourth Department of Internal Medicine – Hematology, Faculty of Medicine, Charles University and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
15 Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University and University Hospital, Brno, Czech Republic
16 Fourth Department of Internal Medicine – Hematology, Faculty of Medicine, Charles University and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
17 Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University and University Hospital, Brno, Czech Republic
18 Data Center, Czech Lymphoma Study Group, Prague, Czech Republic
19 Data Center, Czech Lymphoma Study Group, Prague, Czech Republic
20 Institute of Pathology, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic
21 Institute of Pathology, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic
22 Department of Pathology and Molecular Medicine, Motol and Homolka University Hospital, Prague, Czech Republic
23 Sylvester Comprehensive Cancer Center, Miller School of Medicine, Miami, Florida, United States
24 First Department of Medicine, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic
25 Department of Internal Medicine, Jackson Memorial Hospital, Miller School of Medicine, Miami, Florida, United States
26 Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, Miami, Florida, United States
27 Division of Hematopathology, University of Miami, Miller School of Medicine, Miami, Florida, United States
28 Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida, United States
29 First Department of Medicine, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic
30 Sylvester Comprehensive Cancer Center, Miller School of Medicine, Miami, Florida, United States
ABSTRACT
Background: MZL transformation to DLBCL is associated with shorter survival and represents unmet clinical need. Data on transformed MZL (tMZL), mostly derived from population-based registries and meta-analyses, lack detailed clinical and treatment information. We report treatments and outcomes of the largest cohort of tMZL to date based on the University of Miami (UM) and the Czech Lymphoma Study Group (CZ) collaboration.
Methods: Following centralized pathology review, 249 patients (pts) with biopsy-confirmed tMZL were included: 76 from the UM (n=810; 1995-2025) and 173 from the CZ (n=2183; 1999-2024) databases. Chi-square/Fisher’s exact tests assessed differences between concurrent (c-tMZL-diagnosed concurrently with MZL) and subsequent (s-tMZL) transformations. Cox regression analyzed clinical factors affecting progression-free survival (PFS) and overall survival (OS).
Results: 116 pts with c-tMZL (31UM, 85 CZ) and 133 with s-tMZL (45 UM, 88 CZ) were analyzed. Based on the s-tMZL events, the estimated cumulative incidence rates at 5, 10, and 15 years were 3.1% & 5.3%, 4.2% & 8.0% and 5.4% & 10.9% in CZ and UM cohorts, respectively. The cohorts had comparable characteristics at the time of tMZL diagnosis, including gender, cell-of-origin (COO) of DLBCL (GCB vs Non-GCB), MZL subtype, ECOG (0-1 vs >2), stage (I-II vs III-IV), and LDH. The cohorts only differed by age, with more younger patients in the UM cohort (age≤60 42.1% vs 25.4%, p=0.008). For both cohorts, there were no differences between pts with c-tMZL and s-tMZL with respect to age, gender, COO, ECOG, stage, LDH and IPI score at the time of tMZL diagnosis.
UM and CZ cohorts had similar PFS (5-year rates 47.2% [95% CI, 34.5-59%] vs 49.8% [41.7-57.4%], p=0.752) and OS (69% [55.8-78.9%] vs 56% [47.7-63.5%], p=0.285) post transformation diagnosis. For further analysis we combined the two cohorts. The 5-year PFS and OS of the combined cohort were 49% (95% CI, 42.2-55.5%) and 59.8% (52.9-66%), respectively. Univariable analysis (UVA) showed shorter PFS with s-tMZL (HR 2.02 [95% CI,1.44-2.84], p<0.001), tMZL from SMZL vs EMZL (HR 1.54 [1.02-2.34], p=0.042), age >60 (HR 2.05 [1.39-3.02], p<0.001), ECOG>2 (HR 2.28 [1.62-3.22], p<0.001), advanced stage (HR 2.1 [1.41-3.14], p<0.001), elevated LDH (HR 2.41 [1.66-3.51], p<0.001), intermediate (HR 2.58 [1.39-4.8], p=0.003) and high risk IPI (HR 4.56 [2.61-7.98], p<0.001). UVA for OS identified the same factors, but no difference by the MZL subtype.
In the c-tMZL group without (w/o) CNS disease (n=114), 104 pts (91.2%) were treated with full-dose anthracycline-based regimens (CHOP-like) and had superior PFS (5-year rate 67.5% [95% CI, 56.9-76%], p<0.0001) and OS (74.8% [64.7-82.4%], p<0.001) compared to 13.3% (0.8-43.3%) and 24% (3.8-53.7%) of the 10 pts (8.8%) who received other therapies (other-tx; e.g R-mini-CHOP). Treatment was an independent predictor in multivariable analysis (MVA) on PFS (HR=3.24, p=0.007) and OS (HR=3.97, p=0.002). Intermediate and high-IPI were also associated with inferior PFS (HR=2.85, p=0.040; HR=4.99, p<0.001) and OS (HR=4.54, p=0.01; HR= 6.37, p<0.001), respectively. Pts with s-tMZL w/o CNS (n=120) were treated with salvage + stem cell transplant (SCT) or CAR-T (Sal-A/C), n=16, 13.3%), salvage without A/C (Sal, n=14, 11.7%), CHOP-like (n=62, 51.7%) and other-tx (n=28, 23.3%). PFS (p=0.0042) and OS (p=0.005) differed significantly across treatment groups: 5-year rates for Sal-A/C 65.3% (95% CI, 35-84.1%) and 83.1% (47.2-95.5%), CHOP-like 40.3% (27-53.1%) and 49.4% (34.7-62.4%), Sal 34.3% (11.6-58.7%) and 55.9% (23.1-79.4%) and other-tx 10% (0.9-32.1%) and 30.3% (10.9-52.5%), respectively. MVA using Sal-A/C as the reference, demonstrated shorter PFS in pts treated with Sal (HR 2.85 [95% CI,1.01-7.98] and other-tx (HR 4.1 [1.50-11.21], p=0.006) and shorter OS in pts treated with CHOP-like (HR 3.98 [1.13-14.07], p=0.032) and other-tx (HR 7.6 [2.02-28.65], p=0.003). Intermediate and high-IPI were also associated with inferior PFS (HR=2.62, p=0.029; HR=3.55, p= 0.001) and OS (HR=4.37, p=0.008; HR= 4.61, p=0.002) respectively.
Conclusions: This is the largest study reporting the survival outcomes in tMZL that demonstrates improved survival among pts with c-tMZL treated with CHOP-like and those with s-tMZL treated with Sal-A/C tx.
DISCLOSURES
Georgios N. Pongas, M.D.: MEVOX, ltd - Current equity holder in private company; ADC Therapeutics - Consultancy (Includes expert testimony); BeOne Medicines - Consultancy (Includes expert testimony)