PET/CT Before Autologous Stem Cell Transplantation Predicts Outcome In High-Risk, Relapsed Follicular Lymphoma

First-line immunochemotherapy followed by two years of rituximab (R) maintenance is now the standard of care for high-tumor burden follicular lymphoma (FL). In spite of an old controversy regarding the heterogeneous metabolic activity of FL lesions, either interim or final PET-CT after R-CHOP first-line therapy is now recognize to be strongly predictive of outcome.

At the time of relapse, R-chemotherapy and autologous stem cell transplantation (ASCT) is a recommended option. Though, some patients will relapse quickly while others achieve long-term remissions. We investigated the prognostic value of PET-CT in patients with high-tumor burden relapsed FL treated with salvage R-chemotherapy followed by ASCT.

Seventy-five patients with relapsed FL referred to three French institutions were retrospectively analyzed. Patients with grade 3b follicular lymphoma or transformed into diffuse large B-cell lymphoma were excluded. Patients received second-line immunochemotherapy according to the local physician’s choice. We classified these salvage treatments into three groups: fludarabine-based regimen (n=29, group 1), cytarabine-based regimen (n=31, group 2), or ifosfamide-based regimen (n=15, group 3). PET-CT scans performed after salvage therapy (before ASCT) were included in the analyses. The local investigator’s interpretation of the imaging physician’s scan report defined a positive or negative PET.

Median age was 56 years and 60% were men. Sixty eight patients received ASCT. Among this whole high-risk study population, 87% relapsed before 36 months after R-CHOP and 42% relapsed within 6 months and were therefore considered as R-CHOP refractory, with a median progression free survival (PFS) after R-CHOP first-line therapy of 15 months. Only 21% of the patients received R maintenance after R-CHOP.

PET-CT scans after salvage therapy (before ASCT) were considered negative in 57%/76%/47% among the 3 groups respectively (p=0.06). Median stem cell harvest was higher in group 3-ifosfamide-based (8.3.10⁶) than in both fludarabine and cytarabine-based regimens (4.47 and 4.8.10⁶ respectively, Mann-Whitney p=0.15). Conditioning regimen was BEAM (37%) or Zevalin-BEAM (56%). Thirteen patients received R maintenance after ASCT.

At a median follow-up of 28 months, 26/75 patients relapsed and 62 are alive. At 2 years, median PFS was 63.8%/66%/53.5% and median overall survival (OS) 68%/94%/92% among the 3 groups, respectively.

PFS was only correlated to PET-CT results (p=0.0006). OS was correlated to group of therapy (2-3 versus 1), FLIPI score at relapse and PET-CT negativity. The latter was the strongest OS predictor on a multivariate analysis (p<0.01). On the other hand, age, gender, conditioning regimen, and PFS after R-CHOP (<36 months or even <12 months) were not linked to shorter PFS/OS.

We observed 12% of second non-hematologic cancer.

PET-CT scan negativity after salvage treatment is the most important favourable factor for relapsed/refractory FL patients who receive ASCT.

No relevant conflicts of interest to declare.