Interim and End-of-Treatment 18F-FDG-PET Evaluation of Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with 6 Cycles of Dose-Dense R-CHOP-14 Immunochemotherapy Plus Pegfilgrastim for First-Line Treatment: An Open-Label Clinical Trial in Spain.

DLBCL is the most frequent aggressive non Hodgkin's lymphoma in adults. The International Prognostic Index (IPI) is currently the most used tool to identify different risk patients. The role of an interim PET to early identify patients with bad response to chemotherapy is controversial. However end of therapy PET correlates strongly with progression free survival.

The aim of this analysis is to evaluate the results of an interim PET (after 2 chemotherapy cycles) and PET at the end of treatment (6 chemotherapy cycles of dose-dense R-CHOP) in patients with DLBCL.

This is a prospective clinical trial for patients with DLBCL older than 65 with IPI 0-5 or younger than 65 with IPI 0-2. Treatment consists of 6 cycles of R-CHOP administered every 14 days followed by pegfilgrastim (6 mg per cycle) on day 2. 63 patients, who completed all 6 cycles of chemotherapy and have had both PET evaluations after 2 cycles of R-CHOP and at the end of treatment, have been selected for this sub-analysis. All evaluations were made by combined PET/ CT, except for 14 patients who were evaluated by PET alone. PET was determined to be positive or negative based on the radiology reports. Interim PET results did not change the planned treatment.

109 patients were analyzed for response. 17 patients (15.5%) did not finish 6 cycles of treatment: 2 due to serious adverse events, 3 due to progression disease / stabilization, 5 due to investigators decision and 7 due to death. Over 92 patients who completed 6 cycles of treatment, 63 patients who had both a PET evaluation after 2 cycles of treatment and at the end of treatment, were included in this analysis. Median age was 60 years old (range 18.2-78.9), 30 (47.6%) were older than 65, 32 (51%) were male. Fifty-four (85.7%) had ECOG 0-1. Characteristics of the disease at diagnosis were as follows: stage III-IV: 39 (61.9%), bulky disease: 15 (23.8%), > 2 extra-nodal sites involvement: 4 (6.4%), B symptoms: 15 (23.8%), elevated LDH: 31 (49.2%), elevated beta-2-microglobulin: 20/57 (35.1%), IPI 3-5: 19 (30.2%). Thirty-one (49.2%) patients achieved a negative PET evaluation after 2 R-CHOP cycles and 53 (84.1%) at the end of treatment. Twenty-nine (93.6%) patients with an interim negative PET remained negative at the end of therapy. Among the 32 patients with a positive PET after 2 cycles of therapy, 24 (75%) turned negative at the end of therapy. Patients with bulky disease had a positive interim PET more frequently (66.7% vs 45.8%), but most of them turned negative at the end of treatment (positive PET 6.7%).

An early positive PET is not predictive of a persistent positivity at the end of treatment. In fact, patients with bulky disease more frequently have an early positive PET, but most of them turn negative after 6 cycles of R-CHOP14. On the other hand, an early negative PET is highly predictive of a negative end-of-treatment PET. In conclusion, our data do not support an early intensification of patients with DLBCL with a positive interim PET, although a longer follow-up is necessary to confirm these results.

No relevant conflicts of interest to declare.