Relapsed and Refractory Primary Mediastinal Diffuse Large B-Cell Lymphoma: Outcome with ICE-Based Treatment.

Introduction: Primary mediastinal diffuse large B-cell lymphoma (PMLBL) is a distinct subtype of diffuse large B-cell lymphoma (DLBCL) with specific clinical, molecular and genetic features. The clinical presentation is similar to that of Hodgkin’s lymphoma (HL); this similarity extends to the molecular level based on gene expression profiling revealing PMLBL is more similar to HL than to DLBCL subtypes. At MSKCC, initial therapy for PMLBL pts treated on protocol has employed dose-dense chemotherapy without radiation (RT) with excellent results [Hamlin, et. Al, BJH, 130(5), 2005]. In patients (pts) with relapsed (rel) and primary refractory (ref) disease, outcome with HDT/ASCT is largely undefined. We report MSKCC’s experience with rel and ref PMLBL pts enrolled on sequential protocols with uniform second-line therapy (SLT) followed by HDT/ASCT, analyzed by intent-to-treat from initiation of SLT.

Methods: Forty-two PMLBL pts were retrospectively identified across intent-to-transplant second-line chemotherapy protocols active at MSKCC from 1989 to 2004. Clinical characteristics at the time of rel or ref disease, including KPS, LDH, stage, and extranodal sites were recorded. Second-line age-adjusted IPI (aaIPI) and IPI values were calculated at rel/ref diagnosis. Event-free and overall survivals were assessed.

Results: Patient demographics (n=42) revealed: rel disease 52.4% (n=22), ref 48% (n=20), 95% were <60 yrs. Advanced stage: 43%, LDH > ULN: 60%, KPS < 80%: 26%; aaIPI 0/1/2/3: 29%/21%/31%/14% (n= 40; 2 missing data); IPI 0&1/2/3/4&5: 45%/19%/14%/17%. Median time from initial diagnosis (dx) to dx of rel/ref disease was 7.2 months (range 2.4 to 37 months); 86% of relapses had occurred by 1 year. Initial therapy was CHOP (50%), NHL-15 (41%) [Portlock CS., et. al, Ann. Oncol., 15(10), 2004], or other (9%). 81% of pts (n=34) received a single second-line program prior to HDT/ASCT: ICE 47.5%, RICE 52.5%. Rituximab was included as part of treatment (at anytime) in 62% of cases. Most patients (81%) did not receive RT with their initial therapy, thus allowing RT to be utilized prior to HDT/ASCT (76% of pts). Ultimately, 81% of pts underwent ASCT. EFS and OS for all pts were 60% and 58% respectively, at a median follow-up for surviving pts of 5.9 years (range, 1.4 to 17 yrs) from diagnosis of rel/ref disease. EFS for rel pts compared with ref pts is 68% vs. 50% (p=0.17). EFS of transplant vs. no transplant pts was 71% vs. 12.5% (p=<0.0001). EFS for ICE vs. RICE was 62.5% vs. 64%; Of stage, LDH, and KPS, only stage was prognostic by log rank for EFS. EFS by aaIPI 0/1/2/3 was 83%/56%/54%/17% (p=0.008); EFS by IPI 0&1/2/3/4&5 was 68%/63%/67%/14% (p=0.001).

Conclusions: This represents the largest intent-to-treat assessment of rel and ref PMLBL reporting SLT with HDT/ASCT. It reveals HDT/ASCT for chemosensitive pts with rel or ref PMLBL results in excellent EFS and OS, more similar to rel/ref HL than DLBCL; a rituximab effect on EFS was not evident in this series. The integration of RT as part of SLT prior to HDT/ASCT might have contributed to these favorable results. In the second-line setting, the aaIPI may divide PMLBL into good (0), intermediate (1–2) and poor (3) risk groups.