Contributions
Abstract: S221
Type: Oral Presentation
Session title: Aggressive Lymphoma - Clinical
Background
The standard treatment in patients with diffuse large-B cell lymphoma (DLBCL) relapsed/refractory (R/R) after first line therapy is a cisplatin-containing regimen followed by consolidation with high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) in responsive ones after induction. Bortezomib had proven activity in aggressive lymphomas.
Aims
On these bases, the Fondazione Italiana Linfomi designed the FIL-VERAL12 trial, aimed at evaluating whether the addition of bortezomib to rituximab-cisplatin-cytarabine-dexametasone (BR-DHAP) increases complete response rate (CR, according to Lugano 2007 criteria) prior auto-SCT compared to standard R-DHAP.
Methods
FIL-VERAL12 was a prospective, multicenter, two-arm randomized phase II trial (NCT01805557).The primary study endpoint was CR after 4 courses of R-DHAP or BR-DHAP, assuming a 30% CR for the standard arm and a 50% CR in experimental arm. Inclusion criteria were: patients aged 18-65 years eligible to high-dose therapy, with R/R DLBCL after first line chemoimmunotherapy. Patients were stratified by relapsed or refractory and randomized 1:1 to receive: a) the standard salvage therapy R-DHAP every 28 days for 4 cycles and b) subcutaneous 1.5 mg/ms bortezomib on days 1 and 4 of each 4-week cycle in addition to the same regimen.
Results
From January 2013 to November 2018, 114 patients were screened, and 107 patients that fulfilled the inclusion criteria were enrolled into the trial and randomized to receive R-DHAP or BR-DHAP (54 patients in R-DHAP, 53 in BR-DHAP). Principal clinical characteristics were: median age 57 years (IQR: 48;62); stage III/IV 83 patients (78%); International Prognostic Index (IPI) risk >2 37 (35%). All patients received rituximab and anthracycline-based regimens as first line treatment. Considering the time at relapse, 53 patients (50%) were registered as relapsed (median time at relapse 10.8 months, IQR: 6.9;20.9) and 54 (50%) as refractory (0.9 months, IQR 0.52;1.3). 52 (49%) patients completed the planned 4 cycles of therapy; 55 did not, due to progressive disease in 42, adverse events or clinician decision in 13. At the end of the 4 courses, the pre-auto-SCT response was: CR 29 (27%), Partial Response (PR) 9 (17%); according to arm of randomization, the primary end point was not met, with CR 28% for R-DHAP and 26% for BR-DHAP (p-value 0.563). Fifty patients (44%) performed a consolidation with SCT, 24 in R-DHAP arm and 26 in BR-DHAP arm; auto-SCT was performed in 39 patients and allo-SCT in 11. The addition of bortezomib to standard R-DHAP did not impact the mobilization, with a median number of CD34+ collected of 6.43 x 10^6 cells CD34/kg (IQR: 4.40;9.11) in R-DHAP and 6.78 x 10^6 cells CD34/kg (IQR: 5.00;9.68) in BR-DHAP. Sixty patients died: 49 (82%) due to lymphoma, 1 due to toxicity, 3 due to transplant related mortality, 7 due to other causes. The incidence of adverse events was similar in the two arms, with grade 3-4 haematological toxicities in 96 patients (90%), g3-4 infection in 5 (5%), g3-4 neurotoxicity in 4 (4%). At a median follow-up of 50 months, 2-years PFS was 29% (95%CI: 19.94;41.83) and 41% (27.67;53.84) for R-DHAP and BR-DHAP, respectively; HR 0.65 (0.41;1.02) p 0.062; 2-years OS was 43% (28.98;56.30) and 52% (37.80;64.56) for R-DHAP and BR-DHAP, respectively; HR 0.74 (0.44;1.23) p 0.244.
Conclusion
In the FIL-VERAL12 phase II randomized trial, the addition of bortezomib to R-DHAP did not improve the CR rate pre-auto-SCT of R/R DLBCL patients eligible to high-dose chemotherapy plus SCT; a numerically higher 2-year PFS rate was observed in BR-DHAP arm.
Keyword(s): Bortezomib, Diffuse large B cell lymphoma, Relapsed lymphoma, Stem cell transplant
Abstract: S221
Type: Oral Presentation
Session title: Aggressive Lymphoma - Clinical
Background
The standard treatment in patients with diffuse large-B cell lymphoma (DLBCL) relapsed/refractory (R/R) after first line therapy is a cisplatin-containing regimen followed by consolidation with high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) in responsive ones after induction. Bortezomib had proven activity in aggressive lymphomas.
Aims
On these bases, the Fondazione Italiana Linfomi designed the FIL-VERAL12 trial, aimed at evaluating whether the addition of bortezomib to rituximab-cisplatin-cytarabine-dexametasone (BR-DHAP) increases complete response rate (CR, according to Lugano 2007 criteria) prior auto-SCT compared to standard R-DHAP.
Methods
FIL-VERAL12 was a prospective, multicenter, two-arm randomized phase II trial (NCT01805557).The primary study endpoint was CR after 4 courses of R-DHAP or BR-DHAP, assuming a 30% CR for the standard arm and a 50% CR in experimental arm. Inclusion criteria were: patients aged 18-65 years eligible to high-dose therapy, with R/R DLBCL after first line chemoimmunotherapy. Patients were stratified by relapsed or refractory and randomized 1:1 to receive: a) the standard salvage therapy R-DHAP every 28 days for 4 cycles and b) subcutaneous 1.5 mg/ms bortezomib on days 1 and 4 of each 4-week cycle in addition to the same regimen.
Results
From January 2013 to November 2018, 114 patients were screened, and 107 patients that fulfilled the inclusion criteria were enrolled into the trial and randomized to receive R-DHAP or BR-DHAP (54 patients in R-DHAP, 53 in BR-DHAP). Principal clinical characteristics were: median age 57 years (IQR: 48;62); stage III/IV 83 patients (78%); International Prognostic Index (IPI) risk >2 37 (35%). All patients received rituximab and anthracycline-based regimens as first line treatment. Considering the time at relapse, 53 patients (50%) were registered as relapsed (median time at relapse 10.8 months, IQR: 6.9;20.9) and 54 (50%) as refractory (0.9 months, IQR 0.52;1.3). 52 (49%) patients completed the planned 4 cycles of therapy; 55 did not, due to progressive disease in 42, adverse events or clinician decision in 13. At the end of the 4 courses, the pre-auto-SCT response was: CR 29 (27%), Partial Response (PR) 9 (17%); according to arm of randomization, the primary end point was not met, with CR 28% for R-DHAP and 26% for BR-DHAP (p-value 0.563). Fifty patients (44%) performed a consolidation with SCT, 24 in R-DHAP arm and 26 in BR-DHAP arm; auto-SCT was performed in 39 patients and allo-SCT in 11. The addition of bortezomib to standard R-DHAP did not impact the mobilization, with a median number of CD34+ collected of 6.43 x 10^6 cells CD34/kg (IQR: 4.40;9.11) in R-DHAP and 6.78 x 10^6 cells CD34/kg (IQR: 5.00;9.68) in BR-DHAP. Sixty patients died: 49 (82%) due to lymphoma, 1 due to toxicity, 3 due to transplant related mortality, 7 due to other causes. The incidence of adverse events was similar in the two arms, with grade 3-4 haematological toxicities in 96 patients (90%), g3-4 infection in 5 (5%), g3-4 neurotoxicity in 4 (4%). At a median follow-up of 50 months, 2-years PFS was 29% (95%CI: 19.94;41.83) and 41% (27.67;53.84) for R-DHAP and BR-DHAP, respectively; HR 0.65 (0.41;1.02) p 0.062; 2-years OS was 43% (28.98;56.30) and 52% (37.80;64.56) for R-DHAP and BR-DHAP, respectively; HR 0.74 (0.44;1.23) p 0.244.
Conclusion
In the FIL-VERAL12 phase II randomized trial, the addition of bortezomib to R-DHAP did not improve the CR rate pre-auto-SCT of R/R DLBCL patients eligible to high-dose chemotherapy plus SCT; a numerically higher 2-year PFS rate was observed in BR-DHAP arm.
Keyword(s): Bortezomib, Diffuse large B cell lymphoma, Relapsed lymphoma, Stem cell transplant