Background: The combination of Rituximab and CHOP (R-CHOP) is considered to be the standard treatment for patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Treatment results are still unsatisfactory in a significant proportion of patients, particularly in those with a high-risk disease defined by the IPI score. The use of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) is standard clinical practice for patients with relapsed/refractory DLBCL, while its significance as consolidation in first-line treatment remains unclear. Aims: We analyzed safety and effectiveness of R-CHOP followed by salvage chemotherapy and ASCT for patients with young (<65 years) high-risk DLBCL, defined by an age-adjusted IPI score of 2/3, for whom from 2004 on our institutional guidelines recommended ASCT as consolidation. We analyzed prognostic factors in this group. Methods: The treatment program consisted of 4 cycles R-CHOP-14 followed by 3 cycles of a DHAP-like salvage regimen, R-MICMA (Sorà et al, Cancer 2006; 106: 859), and consolidation with Busulfan-Melphalan supported with ASCT. We observed 76 consecutive patients (median age 50 years, range 15- 64 years; 32 females and 44 males) diagnosed between May 2004 and January 2013 with DLBCL who had an age-adjusted IPI score of 2 or 3. Response was assessed according to Cheson criteria (Cheson et al, JCO 1999; 17:1244). Results: Nine of 76 patients (12%) were not eligible for the treatment program that included ASCT. Reasons were important comorbidities in 6 pts (1 cardiac, 2 neurologic, 1 hepatic, 1 hematologic, 1 renal) and start of another treatment regimen (CODOX-M/IVAC in the suspicion of a Burkitt lymphoma) in 3 pts. Response after 4 cycles R-CHOP was CR/CRu in 40/67 pts (60%), PR in 21/67 pts (31%) and NR in 6/67 (9%). Sixty-one patients went on to salvage chemotherapy with R-MICMA, while 6 pts in CR/CRu continued R-CHOP, and 53 pts were transplanted. Reasons not to proceed to transplant were progressive disease (3 pts), infections (3 pts), mobilization failure (1 pt) and patient’s decision (1 pt). The 3-year EFS and OS of the entire group of 76 patients were 67% (95% CI, 55-76) and 71% (95% CI, 59-80%), respectively. The 3-year EFS and OS of transplanted patients were 70% (95% CI, 55-80) and 76% (95% CI, 62-85). Factors associated with inferior EFS were age-adjusted IPI score (2 vs. 3, p=0.004) and disease status after 4 cycles R-CHOP (p=0.01) in univariate and multivariate analysis. These differences were also retained in the group of patients who received ASCT, with a three-years EFS of 78% in pts with an age-adjusted IPI score 2 vs 46% in pts with an age-adjusted IPI score 3 (p=0.003), suggesting that ASCT is insufficient for highest risk patients. Summary and Conclusions: Our findings of an intention-to-treat, single centre experience indicate that 88% of patients with high-risk DLBCL and age <65 years are eligible for a treatment strategy that includes ASCT, and 70% will eventually receive ASCT as part of their first-line treatment. Consolidation with upfront ASCT for high-risk DLBCL is a feasible and promising therapy also in the Rituximab era, but there are still subsets of patients that continue to have a poor prognosis despite ASCT, and addition of new biologic drugs, as tyrosine kinase inhibitors, have to be tested to improve outcome in these patients.

Tisi, M. C., Maiolo, E., D'Alo', F., Bellesi, S., Sora', F., Chiusolo, P., Laurenti, L., Picardi, M., Alma, E., Larocca, L. M., Sica, S., Hohaus, S., HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANTATION IN FIRST LINE TREATMENT FOR HIGH-RISK DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) IN THE RITUXIMAB ERA: AN INTENTION TO TREAT-ANALYSIS, Abstract de <<19th Congress of the European-Hematology-Association>>, (Milan, ITALY, 12-15 June 2014 ), <<HAEMATOLOGICA>>, 2014; 99 (Supplement no.1): 703-703 [http://hdl.handle.net/10807/62174]

HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANTATION IN FIRST LINE TREATMENT FOR HIGH-RISK DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) IN THE RITUXIMAB ERA: AN INTENTION TO TREAT-ANALYSIS

Tisi, Maria Chiara;Maiolo, Elena;D'Alo', Francesco;Bellesi, Silvia;Sora', Federica;Chiusolo, Patrizia;Laurenti, Luca;Alma, Eleonora;Larocca, Luigi Maria;Sica, Simona;Hohaus, Stefan
2014

Abstract

Background: The combination of Rituximab and CHOP (R-CHOP) is considered to be the standard treatment for patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Treatment results are still unsatisfactory in a significant proportion of patients, particularly in those with a high-risk disease defined by the IPI score. The use of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) is standard clinical practice for patients with relapsed/refractory DLBCL, while its significance as consolidation in first-line treatment remains unclear. Aims: We analyzed safety and effectiveness of R-CHOP followed by salvage chemotherapy and ASCT for patients with young (<65 years) high-risk DLBCL, defined by an age-adjusted IPI score of 2/3, for whom from 2004 on our institutional guidelines recommended ASCT as consolidation. We analyzed prognostic factors in this group. Methods: The treatment program consisted of 4 cycles R-CHOP-14 followed by 3 cycles of a DHAP-like salvage regimen, R-MICMA (Sorà et al, Cancer 2006; 106: 859), and consolidation with Busulfan-Melphalan supported with ASCT. We observed 76 consecutive patients (median age 50 years, range 15- 64 years; 32 females and 44 males) diagnosed between May 2004 and January 2013 with DLBCL who had an age-adjusted IPI score of 2 or 3. Response was assessed according to Cheson criteria (Cheson et al, JCO 1999; 17:1244). Results: Nine of 76 patients (12%) were not eligible for the treatment program that included ASCT. Reasons were important comorbidities in 6 pts (1 cardiac, 2 neurologic, 1 hepatic, 1 hematologic, 1 renal) and start of another treatment regimen (CODOX-M/IVAC in the suspicion of a Burkitt lymphoma) in 3 pts. Response after 4 cycles R-CHOP was CR/CRu in 40/67 pts (60%), PR in 21/67 pts (31%) and NR in 6/67 (9%). Sixty-one patients went on to salvage chemotherapy with R-MICMA, while 6 pts in CR/CRu continued R-CHOP, and 53 pts were transplanted. Reasons not to proceed to transplant were progressive disease (3 pts), infections (3 pts), mobilization failure (1 pt) and patient’s decision (1 pt). The 3-year EFS and OS of the entire group of 76 patients were 67% (95% CI, 55-76) and 71% (95% CI, 59-80%), respectively. The 3-year EFS and OS of transplanted patients were 70% (95% CI, 55-80) and 76% (95% CI, 62-85). Factors associated with inferior EFS were age-adjusted IPI score (2 vs. 3, p=0.004) and disease status after 4 cycles R-CHOP (p=0.01) in univariate and multivariate analysis. These differences were also retained in the group of patients who received ASCT, with a three-years EFS of 78% in pts with an age-adjusted IPI score 2 vs 46% in pts with an age-adjusted IPI score 3 (p=0.003), suggesting that ASCT is insufficient for highest risk patients. Summary and Conclusions: Our findings of an intention-to-treat, single centre experience indicate that 88% of patients with high-risk DLBCL and age <65 years are eligible for a treatment strategy that includes ASCT, and 70% will eventually receive ASCT as part of their first-line treatment. Consolidation with upfront ASCT for high-risk DLBCL is a feasible and promising therapy also in the Rituximab era, but there are still subsets of patients that continue to have a poor prognosis despite ASCT, and addition of new biologic drugs, as tyrosine kinase inhibitors, have to be tested to improve outcome in these patients.
Inglese
Tisi, M. C., Maiolo, E., D'Alo', F., Bellesi, S., Sora', F., Chiusolo, P., Laurenti, L., Picardi, M., Alma, E., Larocca, L. M., Sica, S., Hohaus, S., HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANTATION IN FIRST LINE TREATMENT FOR HIGH-RISK DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) IN THE RITUXIMAB ERA: AN INTENTION TO TREAT-ANALYSIS, Abstract de <<19th Congress of the European-Hematology-Association>>, (Milan, ITALY, 12-15 June 2014 ), <<HAEMATOLOGICA>>, 2014; 99 (Supplement no.1): 703-703 [http://hdl.handle.net/10807/62174]
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