R-CHOP with or without Lenalidomide/Bortezomib As a First Line Treatment for Patients with Non-Germinal Center Diffuse Large B Cell Lymphoma (DLBCL) Subtype: Son Espases University Hospital Experience

Abstract

INTRODUCTIONThe standard first line treatment for patients with diffuse large B-cell lymphoma (DLBCL) is rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) independently of cell origin subtype. Retrospective studies have shown that non-germinal center (NGC) subtype is associated with a worse progression free survival (PFS) and overall survival (OS) compared to germinal center subtype. In phase II studies the combination of lenalidomide (lena) or bortezomib (bor) with R-CHOP in this lymphoma subtype has shown better results in comparison to R-CHOP alone. For this reason, the aim of our study is to analyze the efficacy and toxicity of R-CHOP plus lena/bor in comparison with R-CHOP alone in patients with NGC DLBCL.PATIENTS AND METHODSIn order to avoid selection bias, all patients with NGC DLBCL (confirmed by immunohistochemistry with Hans algorithm) who received R-CHOP or R-CHOP-lena/bor (25mg lenalidomide daily from day 1 to 10 / bortezomib 1.3mg/m2 days 1 and 4) were retrospectively selected from the Pharmacy Registry. Patients in our center received R-CHOP from March 2002 to June 2013, R-CHOP-bor from June 2013 to July 2015 and R-CHOP-lena from November 2014 until now. Cheson and Lugano criteria were used to confirm response rates. Toxicity was checked with CTCAE v4-5 criteria.RESULTSFifty-five patients with NGC DLBCL were identified from 2002 to 2018, 18 of whom were treated with R-CHOP-lena/bor and 33 with R-CHOP. Baseline characteristics are specified in Table 1. Overall response rate was similar in both treatment regimens, 94% versus 87%, respectively. 12.5% progression/stable disease cases were identified with R-CHOP alone compared to 5.3% with R-CHOP-lena/bor. With a median follow-up of 45 months (6-126) for R-CHOP and 22 months (6-59) for R-CHOP-lena/bor, the median PFS was 65 months for R-CHOP and was not reached for R-CHOP-lena/bor. 47% versus 9% of progressions were observed in R-CHOP and R-CHOP-lena/bor, respectively (p=0.006). Regarding OS, the death rate in the R-CHOP group was 45% in comparison with 23% in R-CHOP-lena/bor group (p=0.015). Higher hematological toxicity was observed in the R-CHOP-lena/bor group comparing with R-CHOP: neutropenia (95% versus 68%), grade 3-4 neutropenia (81% versus 37%) and anemia (81% vs 56%) (p<0.05) (Table 2) being manageable in all cases.CONCLUSIONSThe addition of lenalidomide or bortezomib to R-CHOP seems to be a good option in NGC DLBCL, with a lower progression rate, refractoriness and less mortality in comparison with R-CHOP alone. R-CHOP-lena/bor is associated to higher rates of hematological toxicity but manageable in all cases. These retrospective data should be confirmed in ongoing phase III clinical trials. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.