Favorable Outcome of Primary Mediastinal Large B-Cell Lymphoma Patients Treated with Sequential R-CHOP/R- ICE Regimen Omitting Radiation
Authors: Goldschmidt Neta , Paltiel Ora B. , Ben Yehuda Dina , Kleinstern Geffen , Gural Alexander , Libster Diana , Lavie David , Gatt Moshe E. 
Published: October 2019

Abstract
Introduction: Progression-free (PFS) and overall survival (OS) rates for Primary mediastinal large B-cell lymphoma (PMBL) have risen to 84% and 92%, respectively, with the addition of rituximab to standard CHOP. Despite general acceptance of RCHOP as standard of care for Diffuse Large B-Cell lymphoma (DLBCL), many centers recommended alternative regimens for PMBL such as RMACOPB, RVACOPB, RCHOP-RICE and DA-EPOCH-R. The latter was adopted with great worldwide enthusiasm, despite its lack of proven superiority in randomized controlled trials (RCT). The benefits of DA-EPOCH-R include the omission of consolidation radiotherapy (RT), an attractive option in PMBL patients (pts), given their demographic profile-mainly females in their 3rd decade. We aimed to evaluate the PFS, the OS, the number of hospitalization days for treatment, and complications and the need for consolidation RT in a single center in the Rituximab era; where since 2007 over 80% of our pts were treated with the RCHOP-RICE regimen consisting of 4 courses of RCHOP followed by 3 courses of RICE.
Methods: We reviewed the files of all PMBL pts who received 1st-line treatment in Hadassah Medical Center between 8/2002-10/2014, extracting clinical, laboratory and imaging data.
Results: Of the 47 pts, 24 were treated with RCHOP-RICE (80% since 2007), 12 with RMACOPB, 3 with RVACOPB, 6 with RCHOP and 2 with DA-EPOCH-R. Pts were mainly female, with Stage I-II disease, and a high LDH level. Pt characteristics were comparable between the protocols (Table). In total, 21 (45%) of our pts received RT; only 3 pts (12%) treated with RCHOP-RICE compared to 18 pts (78%) treated with other protocols (p<0.01). A mean of 11+8 hospitalization days/pt were needed to administer the RCHOP-RICE regimen, significantly more than required for other treatments combined (p<0.01), except DA-EPOCH-R where the mean hospitalization days to administer 6 courses-=37+2 /pt (2 patients). Treatment-related toxicities did not differ between the groups. Late toxicity included advanced breast cancer in one pt who received RMACOPB and radiotherapy. The Deauville 5-point scale at interim was available for 39 pts, of whom 43% had an uptake </= to mediastinal blood pool, 33% had an uptake greater than the mediastinum and </= liver uptake and 23% had >liver uptake. At the end of therapy the numbers were 68%, 23% and 9% respectively, for 35 pts who were evaluated. The median 5-year PFS and OS were 93% and 98% respectively, with no difference between treatment regimens.
Conclusion: The RCHOP-RICE regimen does not appear inferior to other regimens, allows to omit RT in PMBL and demonstrated no significant late toxicities. Published phase 2 data on DA-EPOCH-R (93% EFS and 95% OS) do not demonstrate an advantage compared to the simpler regimens described here. RCTs are required to establish the standard for efficacy, efficiency and safety of care in PMBL.
Table 1. Characteristics RCHOP-RICE Others All patients Number of patients 24 23 47 Median age 34 34 34 Female n(%) 16 (67) 15 (65) 31 (66) Stage 1-2 n(%) 17 (71) 21 (91) 38 (81) Median tumor size (cm) 10.2 10.5 10.2 High LDH n(%) 21 (87) 17 (81) 38 (84) Effusion n(%) 10 (42) 9 (39) 19 (40) Median 5 year PFS 90% 95% 93% Median 5 year OS 100% 95% 98%

Disclosures
Lavie: Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.