PS1255 EFFICACY OF R-BAC IMMUNOCHEMOTHERAPY IN PATIENTS WITH RELAPSED, REFRACTORY MANTLE CELL LYMPHOMA POST BTK INHIBITOR THERAPY
Authors: R. McCulloch, C. Visco, R. Frewin, D. Tucker, J.P. Kerr, N. Phillips, J. Gandla, M.R. Howard, A. Hodson, F. Jack, J. Seale, N. Crosbie, S. Rule
Journal: HemaSphere (2019)

Background: The prognosis of follicular lymphoma (FL) is considered favorable with rituximab-containing first-line chemotherapy (R-CHEMO1). However, many patients will eventually require second-line therapy, for which there is no current standard. Generally, patients receive a second course of rituximab-containing chemotherapy (R-CHEMO2) even though there are no prospective trials backing this approach. Aims: To characterize outcomes after R-CHEMO2 of patients with relapsed biopsy-proven grade 1–3A FL initially treated with R-CHEMO1 ± maintenance rituximab (MR). Methods: We did a retrospective study of consecutive patients from 6 Canadian centres, excluding patients with transformed FL and those who received second-line radiotherapy or chemotherapy alone. Results: 129 patients with FL, 48% female, were included. Characteristics at diagnosis were a median age of 56 years (range 20–81), 84% stage III/IV, 35% high-risk FLIPI. 33 (26%) were initially observed, and 5 (4%) initially received radiation. R-CHEMO1 was R-CVP in 95 (74%), R-CHOP in 29 (23%), BR in 4 (3%), and FR in one patient. 73 (57%) received MR1. The median time from start of R-CHEMO1 to start of R-CHEMO2 was 36 months (range 2–145), with progression within 24 months of R-CHEMO1 (POD24) in 49 (38%) patients. At start of R-CHEMO2, the median year was 2011 (range 2004–2017), the median age was 60 (range 22–82). 80% had stage III/IV, 44% high-risk FLIPI, 39% high LDH, 89% performance status 0–1. Second-line regimens included 40 (31%) BR, 19 (15%) R-CHOP, 19 (15%) R-CVP, 17 (13%) FR, 17 (13%) platinum-containing, and 17 (13%) other regimens. Overall response rate was 80% and complete response 37%. 40 (31%) patients received autologous stem cell transplantation (ASCT), 34 (26%) received MR2, and 5 received radiotherapy. With a median follow-up in living patients of 5.2 years (range 1.1–13.3) after R-CHEMO2, there have been 56 (43%) instances of progression (PROG2). 20 were biopsied (7 DLBCL, 13 FL) and 36 were not (2 aggressive and 34 indolent behavior). Median PFS2 was 6.4 years (95% CI 3.0–9.9) and 5-year PFS2 was 54% (95% CI 53–55). 31 (24%) patients progressed within 6 months of R-CHEMO2 or MR2. Age over 60 (HR 1.75, 95% CI 1.04–2.95, p = 0.036), ASCT (HR 0.26, 95% CI 0.13–0.53, p < 0.001), and CR to R-CHEMO2 (HR 0.22, 95% CI 0.11–0.44, p < 0.001) were associated with PFS2. Median OS2 was not reached and 5-year OS2 was 81% (95% CI 80–82). 27 patients died at the time of last follow up; 20 from lymphoma, and 7 from other causes. Elevated LDH (HR 3.22, 95% CI 1.42–7.28, p = 0.005), high FLIPI (HR 5.13, 95% CI 2.04–12.86, p < 0.001), ASCT (HR 0.19, 95% CI 0.06–0.64, p = 0.007) and CR to R-CHEMO2 (HR 0.31, 95% CI 0.11–0.89, p = 0.029) were associated with OS2. 53/56 patients with progression after R-CHEMO2 received 3rd line therapy, which was heterogeneous: 35 received R-CHEMO3, 3 ASCT, 9 allogeneic SCT, and many patients received novel/experimental agents. The median time to 3rd line therapy was 1.5 years (range 0.13–8.1). 5-year OS3 of 57% (95% CI 55–59) did not differ according to indolent vs. aggressive behavior (p = 0.306). Summary/Conclusion: Patients with relapsed FL treated with R-CHEMO1 can be successfully treated with R-CHEMO2 and achieve prolonged PFS2 and freedom from 3rd line treatment. Patients under the age of 60, those treated with ASCT, and those who achieve a CR have improved PFS2. Outcomes at progression after R-CHEMO2 are less favorable, highlighting the need for other therapies in these patients. These data may provide benchmarking for clinical trial development and regulatory purposes.