Early Response to a Short Course of Induction Chemotherapy Overcomes the Prognostic Role of IPI in Patients with Aggressive NHL. Preliminary Results of the GISL LA05 Trial.

The achievement of a clinical response to the first part of induction chemotherapy has been considered for predicting survival in patients with aggressive non Hodgkin lymphoma (NHL). In April 2000, the Gruppo Italiano Studio Linfomi (GISL) started the LA05 trial with the aim of assessing different treatment modalities according to response to 4 initial courses of chemotherapy (CT) assessed according to the international response criteria for NHL. Untreated Patients younger than 65 years with histologically confirmed diagnosis of aggressive NHLs were eligible to the study. All stages and all IPI groups were allowed. After 4 courses of CT patients achieving at least a PR >75% were to be treated with two additional courses of CT (group 1); those achieving PR <75% were randomized to receive either additional 4 courses of the same CT or a modified HDS program followed by autologous stem cell support (group 2); patients with SD or PD were to be assigned to salvage programs (group 3). The study CT regimen was ProMECE-CytaBOM; in July 2005, the protocol was amended allowing the use of other CT regimens, including CHOP and MACOP-B, and recommending the addition of Rituximab for B-cell NHL. D The study is still ongoing and we are not yet able to provide data about the efficacy of HDS in patients of group 2. We present the preliminary results of efficacy of the LA05 trial, in particular focused on the outcome of group 1 patients. As of June 2006, 341 patients were enrolled. Eighty percent of cases had DLBCL, 12% PTCL, 5% GIII FL and 3% MCL. Median age at diagnosis was 49 years (range 18–67). Sixty percent had stage III–IV disease and 38% had a bulky mass. IPI was low (0–1) in 52%, intermediate (2) in 22% and high (3+) in 26% of cases. After 4 courses of CT, 265 patients were evaluable for response; one-hundred and seventy patients (64%) achieved a CR or a PR >75%, 49 (19%) achieved a PR <75% and 46 (17%) had SD or PD. The probability of achieving a CR or a PR >75% was 74%, 62% and 42%, for patients with an initial IPI of 0–1, 2 or 3+. At the end of treatment program, a CR was achieved in 57% of cases and a PR in 14%. After a median follow-up of 21 months (range 1–73), the 2-year OS was 69% (IC 95% 62–75), being 85%, 65% and 25% for group 1, 2 and 3 respectively (p<0.001). Two-year OS was 88%, 78% and 78% for patient in group 1 with and IPI of 0–1, 2 and 3+ respectively (p=NS). The achievement of a CR or a PR >75% after the first part of initial CT overcomes the prognostic role of IPI in patients with aggressive NHL.