Retrospective analysis on R‐DHAP/OX and ASCT as salvage treatment for relapsed/refractory high‐risk follicular lymphoma

Abstract

Introduction: Follicular lymphoma (FL) relapsing within the first 2 years from frontline chemo-immunotherapy is associated with a median overall survival of 5 years from the time of progression, and optimal subsequent treatment remains uncertain. Rituximab, dexamethasone, high-dose cytarabine, and cisplatin/oxaliplatin (R-DHAP/Ox), followed by autologous stem cell transplant (ASCT), could be a reasonable option because it has shown efficacy in diffuse large B-cell lymphoma with germinal center subtype. Method(s): We retrospectively analyzed patients with FL relapsing within 2 years after first-line chemo-immunotherapy who received subsequent R-DHAP/Ox. Exclusion criteria were histologic grade 3B and transformation to DLBCL before R-DHAP/Ox. Overall survival (OS) was calculated from risk-defining events as described in the LymphoCare study (Casulo et al. JCO 2015). Time to next therapy (TTNT) was calculated from the end of one line of therapy to start of the subsequent therapy. Survival end points were estimated with the Kaplan-Meyer method. Result(s): Data from 67 patients were collected, from 3 Italian institutions; 48 patients were eligible. Characteristics of the population are summarized in the table. First-line therapy was R-CHOP in 37 (77%), R-fludarabine-mitoxantrone in 4 (8.3%), R-CVP in 2 (4.1%), R-bendamustine in 2 (4.1%), R-FND, R-chlorambucil, and R-HDS (HD sequential of etoposide, cyclophosphamide, mitoxantrone, (Table Presented) melphalan + ASCT) in 1 (2.1%). Thirty-four 34 (70.8%) patients underwent 1 line of therapy prior to R-DHAP/Ox, 11 (22.9%) underwent 2 lines of therapy, and 3 (6.3%) had 3 or more lines before R-DHAP/Ox. The median TTNT from first-line was 14.3 months (range 10.6-19.4). With a median follow-up of 66 months, the 5-year OS was 73.1% (95% CI, 61-85%). Among the 34 patients that underwent ASCT, the 5-year OS was 84% (95% CI, 72-98%). Time to next treatment (TTNT) after DHAP/Ox was 30.9 months (95% CI, 18-47%). Stem cell collection failure was reported in 6 cases (12.5%). Four cases (8.3%) of transformation to DLBCL and 3 (6.2%) secondary malignancies (2 myeloid disorders, 1 bladder carcinoma) were reported. Conclusion(s): In this population of high-risk, early relapsing FL, RDHAP/ Ox +/- ASCT was found to be active, with aTTNT significantly longer than that experienced following first-line therapy. This population had very similar FLIPI risk scores compared to the LymphoCare study population but appears to have experienced better survival outcomes. Late events continue to occur, and cure appears unlikely. Prospective studies of R-DHAP/Ox +/- ASCT are warranted in this high-risk FL population.