Chemoimmunotherapy with R-CHOP or High Dose Sequential Therapy with Autologous Stem Cell Transplantation (R-HDS) for High Risk Diffuse Large B-Cell Lymphomas Patients: Results of the Randomized R-HDS0305 Trial by Gruppo Italiano Terapie Innovative Nei Linfomi (GITIL)

Autor: Giovanni Pizzolo, Pietro Leoni, Atto Billio, Alessandro Massimo Gianni, Arianna Masciulli, Marco Scarano, Valerio Zoli, Antonino Mulè, Maurizio Frezzato, Tiziano Barbui, Anna Maria Barbui, Leonardo Flenghi, Paolo Corradini, Manuela Zanni, Alessandro Rambaldi, Giorgio La Nasa, Sergio Cortelazzo, Roberto Marchioli, Andrea Rossi, Francesco Di Raimondo, Corrado Tarella, Caterina Patti, Andrés J.M. Ferreri, Andrea Gallamini, G. Semenzato, Massimo Di Nicola, Marco Ladetto
Rok vydání: 2012
Předmět:
Zdroj: Blood. 120:746-746
ISSN: 1528-0020
0006-4971
Popis: Abstract 746 Background The clinical benefit of high dose chemotherapy programs in patients with diffuse large B cell lymphomas (DLBCL) with unfavorable presentation (IPI>2) is still matter of debate and several prospective randomized clinical trials have been conducted to address this point. Patients and study design In year 2005 the cooperative study group GITIL launched a multicenter phase III trial (R-HDS 0305, Clinical Trials.gov.number NCT00355199) in DLBCL patients without CNS involvement and the following inclusion criteria: age between 18–60 years, stage > II B-bulk with ECOG-PS=0-3 and age adjusted IPI (aaIPI) 2–3 or age 61–65 years with ECOG-PS = 0–2 and IPI >3. The control group received 8 courses of the conventional R-CHOP-14 chemotherapy program, followed by IFRT, in patients who achieved at least a partial response (PR) after 4 cycles. Cases refractory to R-CHOP-14 could be rescued by R-HDS. The experimental arm (R-HDS) included: 3 courses of doxorubicin-containing chemotherapy (APO), followed by high-dose cyclophosphamide (CTX) 7 g/sqm, Ara-C (2g/sqm every 12 hours for 6 days), etoposide 2 g/sqm plus cisplatin 100 mg/sqm. After R-HDS chemotherapy, a mitoxantrone-melphalan (60 and 180 mg/sqm, respectively) or BEAM conditioning regimen with autologous stem cell transplantation (ASCT) + IFRT, as above. Rituximab (375 mg/sqm) was given for a total of 6 doses, twice after CTX and Ara-C based cycles, as in vivo purging before CD 34+ cells harvest, and twice after ASCT (Tarella C. et al Leukemia 21:1802–1811, 2007). The primary end-point of the study was to test an increase of 2-year Event Free Survival (EFS) from 50% in the R-CHOP arm to 65% in the intensified R-HDS arm. Secondary end-points were Disease Free Survival (DFS), Overall Survival (OS) and toxicity. Results From June 2005 to June 2011, 248 patients were enrolled in the study (R-CHOP-14=127; R-HDS=121) and 241 were evaluable as to completeness of information. The median age was 51 years (range, 18–65), 32 subjects (13.3%) had> 60 years and the M/F ratio was 1.39. Clinical features were as follows: advanced Ann Arbor clinical stage (93%), BM infiltration (22%), bulky disease (69%), elevated LDH (87%), elevated beta 2-microglobulin (60%), poor ECOG-PS (61%), B-symptoms (57%), ≥2 extranodal sites (71%), IPI 2 (51%) and IPI >3 (49%). The two arms were well balanced for all these features. No significant difference could be detected in the response rates of patients treated with R-CHOP and R-HDS that in detail, were the following: complete response (CR, 76% vs. 76%), partial response (PR, 4.7% vs. 7.9%), progressive disease (PD, 15% vs. 8.8%), stable disease (SD, 1.6% vs. 0.9%), treatment discontinuation for any reason (0 vs. 1.8%), early death (ED, 2.4% vs. 4.4%). On the contrary, the relapse rate was higher in the R-CHOP vs. the R-HDS arm (14% vs. 4.6%, p= 0.025). After a median follow-up of 27.7 months (range 0.3 – 52.5) the 2-year DFS of patients treated with R-CHOP or R-HDS is 83% vs. 93% (p=0.07) while the EFS is 68% vs. 73% (p= 0.345) (Figure 1 and 2). Similarly, with the current follow up, no significant difference could be detected in OS (77% vs. 80%, p= 0.398). The OS was better for patients with IPI 2 in comparison to those with IPI >3 (84% vs. 73%; p= 0.04), but without any significant difference according to treatment arm. Although the rate of death in remission (2% in both arms) was similar, the overall toxicity of the R-HDS arm was higher in terms of hematologic toxicity (CTC G>2) (p Conclusion In DLBCL patients with unfavorable presentation a conventional R-CHOP and a more intensive R-HDS chemotherapy achieved the same excellent rate of response. Despite a trend for a better DFS observed in patients treated with R-HDS, the EFS (primary endpoint of the study) and the OS are not different. A longer follow-up is needed in order to definitively rule out the role of intensified R-HDS program as first line treatment for poor-prognosis DLBCL patients. Disclosures: Tarella: Hoffmann-La Roche: Consultancy, Honoraria. Gianni:Hoffmann-La Roche: Consultancy, Honoraria. Pizzolo:Hoffmann-La Roche: Consultancy, Honoraria. Rambaldi:Hoffmann-La Roche: Consultancy, Honoraria.
Databáze: OpenAIRE
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