Contributions
Abstract: PB1793
Type: Publication Only
Background
Diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable B cell tumor, characterized by an extreme biological complexity and different clinical outcomes. Recent studies suggested that the use of front-line high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in untreated high-risk DLBCL does not improve the outcome, while this approach remains the standard of care for chemosensitive relapse/refractory (R/R) DLBCL. However, the outcome of many R/R DLBCL still remains unsatisfactory.
Aims
We analyzed the outcome and toxicities in a cohort of DLBCL patients treated with HDT and ASCT as first-line or salvage approach at our centre.
Methods
We retrospectively evaluated a group of 34 high-risk DLBCL patients, who underwent ASCT (12 as first-line and 22 as salvage regimens). Median age at diagnosis was 50 years (range 21-70 years). Adverse clinical features in the upfront HDT and R/R groups, were: Ann Arbor stage III to IV (77% vs 86%), ECOG ≥2 (25% vs 10%), bulky disease (58% vs 45%), ≥2 extranodal sites (25% vs 32%), B symptoms (67% vs 41%), R-IPI poor (58% vs 68%), CNS-IPI intermediate to high-risk (83% vs 86%), primary refractory/early relapse (42% vs 77%), cell of origin (COO as per Hans’ immunohistochemistry (IHC) algorythm: GCB 33% vs 36% and non-GCB 42% vs 50%), BCL2 positivity in IHC (50% vs 73%), high proliferation index (Ki67 ≥70: 42% vs 45%). c-Myc was evaluated only in 8/34 patients (23%). Cytogenetics and FISH analysis were performed at diagnosis in 30/34 patients (88%). Results were: poor/complex karyotype (17% vs 23%) and double hit lymphoma (2 patients in the upfront HDT group vs 1 patients in the R/R group). Salvage regimens were R-DHAP, R-ICE or R-CODOX/IVAC; ASCT conditioning was BEAM (10 patients), BEAM-like (15 patients) or Mitox/L-PAM (7 patients). Response was assessed using the revised Lugano criteria.
Results
There were not significant differences in CR rate, OS and PFS between the upfront HDT and R/R group (CR: 58% vs 55%, p=0.9; 3-year OS: 54.5% vs 58.4%, p=0.9; 3-year PFS: 56.3% vs 59.1%, p=0.9). Grade ³3 hematological and non-hematological adverse events were reported in 58% patients in the upfront HDT group versus 55% patients in the R/R group. Conditioning regimens provided comparable results, both in term of toxicity and efficacy against lymphoma. Five patients (42%) in the upfront HDT group and nine patients (41%) in the R/R group died. No differences in OS and PFS were observed according to the COO, BCL2 positivity, lymphocyte/monocyte ratio at diagnosis and subdiaphragmatic disease. The presence of R-IPI poor and Ki67≥70% at diagnosis significantly impacted on OS and PFS (for R-IPI poor, 3-year OS 45%, p=0.07, 3-year PFS 46%, p=0.05; for Ki67≥70%, 3-year OS 30%, p=0.03, 3-year PFS 33%, p=0.03: data confirmed also in multivariate analysis).
Conclusion
Our analysis is a “real life” experience of treatment choices for high risk DLBCL; we confirmed that front-line HDT followed by ASCT in untreated high-risk DLBCL does not improve CR, PFS and OS, compared to ASCT in the R/R setting. Hematologic and non-hematologic toxicities were similar in the upfront HDT and R/R groups. Importantly, in our cohort an high R-IPI and elevated Ki67 positivity at diagnosis significantly impacted on OS and PFS. These markers together with other recognized prognostic factors validated in the R/R setting (as described in the CORAL study and in REFINE analysis), should be assessed to help discriminate patients in which conventional salvage therapies is not appropriate.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): DLBCL
Abstract: PB1793
Type: Publication Only
Background
Diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable B cell tumor, characterized by an extreme biological complexity and different clinical outcomes. Recent studies suggested that the use of front-line high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in untreated high-risk DLBCL does not improve the outcome, while this approach remains the standard of care for chemosensitive relapse/refractory (R/R) DLBCL. However, the outcome of many R/R DLBCL still remains unsatisfactory.
Aims
We analyzed the outcome and toxicities in a cohort of DLBCL patients treated with HDT and ASCT as first-line or salvage approach at our centre.
Methods
We retrospectively evaluated a group of 34 high-risk DLBCL patients, who underwent ASCT (12 as first-line and 22 as salvage regimens). Median age at diagnosis was 50 years (range 21-70 years). Adverse clinical features in the upfront HDT and R/R groups, were: Ann Arbor stage III to IV (77% vs 86%), ECOG ≥2 (25% vs 10%), bulky disease (58% vs 45%), ≥2 extranodal sites (25% vs 32%), B symptoms (67% vs 41%), R-IPI poor (58% vs 68%), CNS-IPI intermediate to high-risk (83% vs 86%), primary refractory/early relapse (42% vs 77%), cell of origin (COO as per Hans’ immunohistochemistry (IHC) algorythm: GCB 33% vs 36% and non-GCB 42% vs 50%), BCL2 positivity in IHC (50% vs 73%), high proliferation index (Ki67 ≥70: 42% vs 45%). c-Myc was evaluated only in 8/34 patients (23%). Cytogenetics and FISH analysis were performed at diagnosis in 30/34 patients (88%). Results were: poor/complex karyotype (17% vs 23%) and double hit lymphoma (2 patients in the upfront HDT group vs 1 patients in the R/R group). Salvage regimens were R-DHAP, R-ICE or R-CODOX/IVAC; ASCT conditioning was BEAM (10 patients), BEAM-like (15 patients) or Mitox/L-PAM (7 patients). Response was assessed using the revised Lugano criteria.
Results
There were not significant differences in CR rate, OS and PFS between the upfront HDT and R/R group (CR: 58% vs 55%, p=0.9; 3-year OS: 54.5% vs 58.4%, p=0.9; 3-year PFS: 56.3% vs 59.1%, p=0.9). Grade ³3 hematological and non-hematological adverse events were reported in 58% patients in the upfront HDT group versus 55% patients in the R/R group. Conditioning regimens provided comparable results, both in term of toxicity and efficacy against lymphoma. Five patients (42%) in the upfront HDT group and nine patients (41%) in the R/R group died. No differences in OS and PFS were observed according to the COO, BCL2 positivity, lymphocyte/monocyte ratio at diagnosis and subdiaphragmatic disease. The presence of R-IPI poor and Ki67≥70% at diagnosis significantly impacted on OS and PFS (for R-IPI poor, 3-year OS 45%, p=0.07, 3-year PFS 46%, p=0.05; for Ki67≥70%, 3-year OS 30%, p=0.03, 3-year PFS 33%, p=0.03: data confirmed also in multivariate analysis).
Conclusion
Our analysis is a “real life” experience of treatment choices for high risk DLBCL; we confirmed that front-line HDT followed by ASCT in untreated high-risk DLBCL does not improve CR, PFS and OS, compared to ASCT in the R/R setting. Hematologic and non-hematologic toxicities were similar in the upfront HDT and R/R groups. Importantly, in our cohort an high R-IPI and elevated Ki67 positivity at diagnosis significantly impacted on OS and PFS. These markers together with other recognized prognostic factors validated in the R/R setting (as described in the CORAL study and in REFINE analysis), should be assessed to help discriminate patients in which conventional salvage therapies is not appropriate.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): DLBCL