Favorable Outcome of Primary Mediastinal Large B-Cell Lymphoma Patients Treated with Sequential R-CHOP/R- ICE Regimen Omitting Radiation

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.

 

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%