PS1254 CHARACTERISTICS AND OUTCOME OF PATIENTS WITH RELAPSED FOLLICULAR LYMPHOMA AFTER RETREATMENT WITH SECOND‐LINE RITUXIMAB‐CONTAINING CHEMOTHERAPY
Authors: Liu J. , Biccler J.L. , Stewart D. , Fontaine A. , Fleury I. , Mollica L. , Prica A. , Buckstein R. , Kuruvilla J. , Villa D. 
Published: June 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.