High Dose Therapy and Autologous Stem Cell Transplantation Still Improves Progression Free Survival in First Relapse for DLBCL in the Rituximab Era: A Study Using Patients as Their Own Controls.
Authors: Sureda Anna , Canals Carme , Mounier Nicolas , Foa Roberto , Conde Eulogio , Maertens Johan , Rambaldi Alessandro , Masszi Tamas , Crawley Charles , Cook Gordon , Attal Michel , Pfreundschuh Michael , Harousseau Jean-Luc , Gisselbrecht Christian 
Published: April 2020

Abstract
Autologous stem cell transplantation (ASCT) remains the treatment of choice for patients (pts) with diffuse large B-cell lymphoma (DLBCL) that relapse after first line chemotherapy (CT). Nevertheless, the impact of the use of the anti-CD20 monoclonal antibody (Rituximab®) (RTX) with combination CT on the ulterior results of the transplantation procedure has to be determined. One of the main factors affecting survival after ASCT is a short first remission duration. This study was designed to evaluate the benefit of this strategy, in pts with DLBCL achieving after salvage CT a 2nd complete remission (CR2), by retrospectively comparing for each pt the progression free survival (PFS) after ASCT with the duration of the previous CR. Adult DLBCL pts with MEDB information available autografted in CR2 between 1990 and 2005 in EBMT centres were included in the analysis. A total of 386 pts (224 males, median age 47 (18–71) years] were evaluated. 294 pts (74%) did not receive RTX prior to ASCT, 67 pts (17%) did receive it at all and in 34 pts (9%) this information is missing. Duration of CR1 was 12 (3 – 142) months [median (range)]; it lasted less than 6 months in 25% of the cases and was longer than 24 months in 25% of the pts. Median time from diagnosis to ASCT was 25 (6–181) months. Peripheral blood was used as the source of hematopoietic stem cells in 311 pts (81%). The BEAM protocol was the conditioning regimen most frequently used (n = 244, 63%) and only 5.5% pts were conditioned with TBI-containing regimens. After a median follow up after ASCT for surviving pts of 42 months, overall survival (OS) was 63% and PFS 48%. 158 pts did relapse after ASCT [median (range), 10 (3–200) months] and 32 pts died from non-relapse mortality. When each patient was taken as her/his own control, PFS after ASCT was longer than CR1 (p &lt; 0.001). During the initial phase of the disease, 74% pts experienced 1st relapse in less than 2 years, compared with only 32% of the patients who experienced 2nd relapse 2 years after ASCT. The use of RTX prior to ASCT did not impair the beneficial effects of the autologous procedure in the whole population of pts (RTX no: 66% vs 33%, p &lt; 0.001; RTX yes: 73% vs 26%, p = 0.001). 2-years PFS after ASCT was significantly lower in patients with a CR1 &lt; 12 months (p &lt; 0.001). However, in this subgroup of patients PFS after ASCT was significantly longer than CR1 duration when studying each pt as his/her own control (p = 0.001). ASCT can significantly increase PFS in comparison with the duration of CR2 in DLBCL and can change disease course. The use of RTX prior to ASCT does not decrease the beneficial effect of pts autografted in CR2 when compared to their prior CR1 duration. The duration of CR1 remains one of the most important prognostic factors for ASCT outcome.