Intensification treatment based on early FDG‐PET in patients with high‐risk diffuse large B‐cell lymphoma: a phase II GELTAMO trial

Abstract

SummaryWe conducted a multicentre, phase II study of interim positron emission tomography (PET) as a guide to risk-adapted therapy in high-risk patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients achieving negative fluorodeoxyglucose (FDG)-PET after three courses of RMegaCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) received three additional courses, whereas PET-positive patients received two courses of R-IFE (rituximab, ifosfamide, etoposide) followed by BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stemcell transplantation. The primary endpoint was progression-free survival (PFS). 71 patients (median age 55 years, range 25-69) were enrolled. With a median follow-up of 42Á8 months (range 7Á2-58Á4), the estimated 4-year PFS and overall survival (OS) were 67% and 78%, respectively, for the global series. Patients in complete remission after interim PET (N = 36) had significantly better 3-year PFS than those with partial response (N = 30) [81% vs. 57%, Hazard ratio (HR) = 2Á6, 95% confidence interval (CI) = 1Á02-6Á65] but not a statistically significant longer OS. A retrospective PET central review was done for 51 patients. According to semiquantitative analysis, 3-year PFS (81% vs. 33%; HR = 6Á9, 95% CI = 2Á35-20Á6) and OS (95% vs. 33%, HR = 19Á4, 95% CI = 3Á89-97Á0) were significantly better for negative than for positive interim PET patients. Early PET assessment is valuable for risk stratification in DLBCL; for this purpose semiquantitative evaluation is a better predictor than visual criteria.

Early treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14

“…[22][23][24] Notably, these trials showed higher rates of iPET-positivity of 39%, 51%, and 71%, compared to 29% in the present study, meaning that more patients were subject to HDT yet still displayed rates of 2-year PFS (66%, 57%, and 65%) that were no better than those seen in the current study (67%). Other notable differences with these 3 studies were that iPET scans were performed earlier in the treatment course (after 2 or 3 induction cycles), and that the 5-PS was not utilized.…”

“…Few studies in DLBCL have prospectively explored a change in treatment strategy guided by iPET responses. [22][23][24][25] We chose to evaluate a change to HDT since it is the most widely accepted curative strategy for patients with DLBCL failing R-CHOP. We hypothesized that improved clinical outcomes for high-risk DLBCL patients with poor prognosis as identified by iPET after 4 chemotherapy cycles would be achieved with early HDT and ASCT delivered when there is a lower burden of chemo-resistant disease than if instituted at the time of radiological progression.…”

Spanish Lymphoma Group (GELTAMO) guidelines for the diagnosis, staging, treatment, and follow-up of diffuse large B-cell lymphoma

“…CMR on iPET carries an excellent prognosis. Studies evaluating intensification treatment based on iPET have shown no benefit over R-CHOP [69, 70]. Therefore, iPET is not recommended as a basis for altering treatment outside of clinical trials.…”

The Strategies to Homogenize PET/CT Metrics: The Case of Onco-Haematological Clinical Trials

“…In the GELTAMO-2006 [50] clinical trial from Grupo Espanol de Linfomas y Trasplante de Medula Osea (GELTAMO) conducted in 20 Spanish hospitals, 71 patients with untreated, histologically proven DLCBL or grade 3B follicular lymphoma CD20+ that had a baseline PET/CT scan positive with at least one evaluable hyper-metabolic lesion were enrolled. Patients achieving negative PET/CT after three courses of R-MegaCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) received three additional courses, whereas PET-positive patients received two courses of R-IFE (rituximab, ifosfamide, etoposide) followed by BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stem-cell transplantation.…”