Contributions
Abstract: PB2217
Type: Publication Only
Background
Bortezomib-based triplet therapy is the current standard of care for induction treatment in myeloma prior to autologous stem cell transplant (ASCT) in combination with dexamethasone and an IMiD such as thalidomide (VTD) or an alkylator such as cyclophosphamide (VCD). Induction therapy aims to achieve the deepest remission whilst limiting treatment toxicity. Peripheral neuropathy secondary to bortezomib and thalidomide can result in dose reduction or treatment discontinuation and potentially poorer response. Substituting thalidomide for cyclophosphamide may limit neuropathy but could theoretically reduce efficacy due to losing the synergistic effect between bortezomib and thalidomide.
Aims
To compare the response to treatment, incidence of neuropathy and rate of bortezomib and thalidomide dose reduction or discontinuation in patients who received VTD vs VCD induction for newly diagnosed myeloma prior to ASCT.
Methods
Patients were treated in 2 consecutive cohorts. Response rates were assessed prior to ASCT using IMWG criteria.
Results
Between 2014 and 2017, 39 patients were treated with VTD and subsequently, a further 30 were treated with VCD. Median age at diagnosis was 62 years and 63 years and the median performance status was 1 and 0, respectively. ORR was 86.8% with VTD and 96.5% with VCD. The rate of VGPR or better was higher in the VTD group (61.5% vs 53%). 4 patients (10.25%) in the VTD group and 1 patient (3.3%) in the VCD group progressed during treatment, with 3 of 4 in the VTD group having high-risk cytogenetics. More patients treated with VTD proceeded to ASCT (84.6% vs 70%). Median follow up was 16 months. The 1-year PFS was 87% for VTD vs 76.5% for VCD. Comparing VTD to VCD, the median total cumulative bortezomib dose was 20.8 mg/m2 vs 24 mg/m2 and the median number of cycles given was 4 and 5 respectively. 14 patients (35.9%) with VTD developed neuropathy of any grade compared to 13 (43.3%) with VCD leading to dose reduction in 20.5% and 43.3% respectively. Median cumulative bortezomib dose prior to the first bortezomib dose reduction was 12.45 mg/m2 with VTD and 16.1 mg/m2 with VCD. The rate of bortezomib discontinuation due to neuropathy (all grades) was 10% in each group. 15 patients (38.5%) treated with VTD had thalidomide dose reduction and 13 (33.3%) discontinued it after a median of 4 cycles. Median bortezomib dose per patient before discontinuation was 10.63 mg/m2 for VTD and 19.43 mg/m2 for VCD.
Conclusion
ORR was higher in patients treated with VCD, with 96.5% achieving remission. Patients treated with VTD required earlier dose reductions of bortezomib and received a lower median dose. Whilst patients treated with VTD achieved a higher rate of VGPR or better, VCD still resulted in an impressive 53% VGPR or above. VGPR rate for VCD is higher than that seen in some previous studies and comparable to that in the IFM2013-04 trial although our results were achieved using a lower dose of cyclophosphamide (500mg weekly). 1-year PFS was higher in the VTD group but more patients in this arm proceeded to ASCT so the PFS data may not accurately reflect the efficacy of induction therapy. Interestingly the rate of neuropathy was higher with VCD. This may reflect the need for more active dose reduction of bortezomib in the VTD group, discontinuation of thalidomide in around one-third of VTD patients and the higher cumulative bortezomib dose in VCD patients. Our findings suggest VCD is effective, delivers a higher bortezomib dose and is a viable alternative to VTD for induction therapy in myeloma.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): bortezomib, Thalidomide
Abstract: PB2217
Type: Publication Only
Background
Bortezomib-based triplet therapy is the current standard of care for induction treatment in myeloma prior to autologous stem cell transplant (ASCT) in combination with dexamethasone and an IMiD such as thalidomide (VTD) or an alkylator such as cyclophosphamide (VCD). Induction therapy aims to achieve the deepest remission whilst limiting treatment toxicity. Peripheral neuropathy secondary to bortezomib and thalidomide can result in dose reduction or treatment discontinuation and potentially poorer response. Substituting thalidomide for cyclophosphamide may limit neuropathy but could theoretically reduce efficacy due to losing the synergistic effect between bortezomib and thalidomide.
Aims
To compare the response to treatment, incidence of neuropathy and rate of bortezomib and thalidomide dose reduction or discontinuation in patients who received VTD vs VCD induction for newly diagnosed myeloma prior to ASCT.
Methods
Patients were treated in 2 consecutive cohorts. Response rates were assessed prior to ASCT using IMWG criteria.
Results
Between 2014 and 2017, 39 patients were treated with VTD and subsequently, a further 30 were treated with VCD. Median age at diagnosis was 62 years and 63 years and the median performance status was 1 and 0, respectively. ORR was 86.8% with VTD and 96.5% with VCD. The rate of VGPR or better was higher in the VTD group (61.5% vs 53%). 4 patients (10.25%) in the VTD group and 1 patient (3.3%) in the VCD group progressed during treatment, with 3 of 4 in the VTD group having high-risk cytogenetics. More patients treated with VTD proceeded to ASCT (84.6% vs 70%). Median follow up was 16 months. The 1-year PFS was 87% for VTD vs 76.5% for VCD. Comparing VTD to VCD, the median total cumulative bortezomib dose was 20.8 mg/m2 vs 24 mg/m2 and the median number of cycles given was 4 and 5 respectively. 14 patients (35.9%) with VTD developed neuropathy of any grade compared to 13 (43.3%) with VCD leading to dose reduction in 20.5% and 43.3% respectively. Median cumulative bortezomib dose prior to the first bortezomib dose reduction was 12.45 mg/m2 with VTD and 16.1 mg/m2 with VCD. The rate of bortezomib discontinuation due to neuropathy (all grades) was 10% in each group. 15 patients (38.5%) treated with VTD had thalidomide dose reduction and 13 (33.3%) discontinued it after a median of 4 cycles. Median bortezomib dose per patient before discontinuation was 10.63 mg/m2 for VTD and 19.43 mg/m2 for VCD.
Conclusion
ORR was higher in patients treated with VCD, with 96.5% achieving remission. Patients treated with VTD required earlier dose reductions of bortezomib and received a lower median dose. Whilst patients treated with VTD achieved a higher rate of VGPR or better, VCD still resulted in an impressive 53% VGPR or above. VGPR rate for VCD is higher than that seen in some previous studies and comparable to that in the IFM2013-04 trial although our results were achieved using a lower dose of cyclophosphamide (500mg weekly). 1-year PFS was higher in the VTD group but more patients in this arm proceeded to ASCT so the PFS data may not accurately reflect the efficacy of induction therapy. Interestingly the rate of neuropathy was higher with VCD. This may reflect the need for more active dose reduction of bortezomib in the VTD group, discontinuation of thalidomide in around one-third of VTD patients and the higher cumulative bortezomib dose in VCD patients. Our findings suggest VCD is effective, delivers a higher bortezomib dose and is a viable alternative to VTD for induction therapy in myeloma.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): bortezomib, Thalidomide