Outcome of Patients with Chemotherapy Refractory and Early Progressive Diffuse Large B Cell Lymphoma After R-CHOP Treatment

The addition of rituximab to CHOP (R-CHOP) has markedly improved the progression-free and overall survival of patients (pts) with diffuse large B cell lymphoma (DLBCL). Nevertheless, 9.5% of pts harbor lymphoma that is refractory to R-CHOP (Feugier et al) and 18–27% experience relapse after initial response (GELA and MINT trial).

Assess outcome of pts with primary refractory and early relapsing DLBCL (within 3 months of CR/PR post completion of R-CHOP treatment).

The BCCA Lymphoid Cancer Database identified 1126 pts diagnosed with DLBCL between December 2000 and September 2009. All ages and stages were included and primary treatment was R-CHOP in all pts.

166 pts(15%) had primary refractory or early relapsing disease, of which 93 were age >70 y and too frail to have received > 2 cycles of R-CHOP. Of the remaining 73 pts, 33 (45%) had primary refractory lymphoma and 40 (55 %) relapsed within 3 months of achieving a CR/PR. Pt characteristics (n=73): median age 57 y; 68% male; stage I (4 %), II (16 %), III (19 %), IV (60 %); PS 0,1 (41 %) PS 2–4 (59 %); LDH elevated (58 %); IPI 0 (1 %), 1 (15 %), 2 (15 %), 3 (30 %), 4 (35 %), 5 (2 %). There were no differences in the clinical characteristics of pts with primary refractory versus early relapsing disease. Of the 73 pts, 37 (50%) were without serious co-morbidity and were able to be treated with a curative intent that included multi-agent salvage chemotherapy with a plan to proceed to high-dose tx and autologous stem cell transplantation (ASCT), whereas 36 pts had palliative tx or comfort care only. 10 pts did undergo ASCT (3 primary refractory, 7 early relapsers). The median overall survival for the 73 pts was 10 months with only 6 pts alive without evidence of disease (range 14–106 months). 5 of these 6 pts had relapsed early after initial CR/PR, while only 1 patient had primary refractory disease. 3 of these 6 pts had salvage treatment without ASCT and 3 with ASCT.

Chemotherapy-refractory or early relapsed disease after R-CHOP has a very poor outcome with only anecdotal survivors independent of the intended treatment approach. Biologic workup of this group of patients is urgently needed with the intention of defining the molecular underpinnings of treatment resistance.

Savage:Roche: Honoraria. Sehn:Roche: Honoraria, Research Funding.