Contributions
Abstract: EP1042
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Ixazomib, lenalidomide and dexamethasone (IRD) provide an efficient treatment for relapsed and/or refractory multiple myeloma (MM) based on the results of the TOURMALINE-MM1 study. Our recent analysis1 showed that the IRD combination has a survival benefit over lenalidomide and dexamethasone alone (RD) in the routine practice.
In the registration trial, the subgroups with greater benefit included patients with 2 or 3 prior therapies, or 1 prior therapy without transplant. Our analysis showed better results in the first relapse with no adverse impact of previous autologous stem cell transplant (ASCT) on the outcome.
Aims
The aim of the present analysis was to determine which subgroups had adverse outcomes regardless of treatment used.
Methods
We assessed a group of 127 patients with relapsed and/or refractory MM treated with IRD and 217 patients with RD regimen. With known data on PFS (17,5 vs 11,5 months) and OS (36,6 vs 26,0 months) we looked for the subgroups who did not benefit from either therapy.
The analyzed parameters were: age (≤65, 66-75, >75 years), ISS stage, cytogenetics, presence of extramedullary disease (EM), line of treatment, maximal treatment response, pretreatment by proteasome inhibitors (PI), immunomodulatory drugs (IMiDs) or ASCT, disease status (relapsed vs relapsed and refractory).
Results
We previously reported adverse impact of EM in both IRD and RD arms (PFS 6,5 and 10,5 months), decreasing PFS with number of prior lines (1 line 32.7 vs 14.8 months, 2 lines 23.1 vs 9.3 months, 3 lines 9.7 vs 9.0 months and ≥4 lines 5.0 vs 9.9 months), with increasing age (≤65 years: 23.0 vs 10.8 months, 66-75 years: 17.8 vs 11.5 months, >75 years: 11.1 vs 11.7 years), more advanced disease by ISS stage (ISS 1 32.7 vs 17.1 months, ISS 2 25.8 vs 9.7 months, ISS 3 9.9 vs 6.4 months), and that there was no adverse impact of previous ASCT – patients after ASCT did better in IRD than RD arm (PFS 23.0 vs 9.7 months).1
The subsequent subgroup analysis showed following results: There was only a limited number of patients with known high-risk cytogenetics (IRD 15, RD 19), still, with a trend to negative impact on PFS (7,3 and 9,9 months). Pretreatment with PIs did not significantly affect the outcomes. There was, however, negative impact of exposure to IMiDs in both IRD (PFS 11,3 months vs not reached) and RD arms (PFS 9,3 vs 18,0 months). Patients who were relapsed and refractory did worse to those who were relapsed only in both IRD (PFS 9,7 months vs not reached) and RD arms (PFS 6,0 vs 14,8 months).
Conclusion
Most of the subgroups that do not benefit with either treatment, correlate with either patient´s overall condition or the aggressiveness of the disease itself. Groups with worse outcomes were as follows: later relapse (≥4), higher age (≥75 years), the presence of high risk features – extramedullary disease, high-risk cytogenetics, higher stage (ISS 3) and refractory status in the previous line. We did not find an adverse impact of pretreatment by PIs or ASCT but patients with previous IMiDs had worse outcomes in both IRD and RD arms.
With support of AZV 17-29343A, NV18–03-00500, MH CZ – DRO (FNOl, 00098892), IGA-LF-2020-002.
1) Minarik J, Pika T, Radocha J. et al. Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice. BMC Cancer 2021; 21: https://doi.org/10.1186/s12885-020-07732-1
Keyword(s): Myeloma, Relapse, Therapy
Abstract: EP1042
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Ixazomib, lenalidomide and dexamethasone (IRD) provide an efficient treatment for relapsed and/or refractory multiple myeloma (MM) based on the results of the TOURMALINE-MM1 study. Our recent analysis1 showed that the IRD combination has a survival benefit over lenalidomide and dexamethasone alone (RD) in the routine practice.
In the registration trial, the subgroups with greater benefit included patients with 2 or 3 prior therapies, or 1 prior therapy without transplant. Our analysis showed better results in the first relapse with no adverse impact of previous autologous stem cell transplant (ASCT) on the outcome.
Aims
The aim of the present analysis was to determine which subgroups had adverse outcomes regardless of treatment used.
Methods
We assessed a group of 127 patients with relapsed and/or refractory MM treated with IRD and 217 patients with RD regimen. With known data on PFS (17,5 vs 11,5 months) and OS (36,6 vs 26,0 months) we looked for the subgroups who did not benefit from either therapy.
The analyzed parameters were: age (≤65, 66-75, >75 years), ISS stage, cytogenetics, presence of extramedullary disease (EM), line of treatment, maximal treatment response, pretreatment by proteasome inhibitors (PI), immunomodulatory drugs (IMiDs) or ASCT, disease status (relapsed vs relapsed and refractory).
Results
We previously reported adverse impact of EM in both IRD and RD arms (PFS 6,5 and 10,5 months), decreasing PFS with number of prior lines (1 line 32.7 vs 14.8 months, 2 lines 23.1 vs 9.3 months, 3 lines 9.7 vs 9.0 months and ≥4 lines 5.0 vs 9.9 months), with increasing age (≤65 years: 23.0 vs 10.8 months, 66-75 years: 17.8 vs 11.5 months, >75 years: 11.1 vs 11.7 years), more advanced disease by ISS stage (ISS 1 32.7 vs 17.1 months, ISS 2 25.8 vs 9.7 months, ISS 3 9.9 vs 6.4 months), and that there was no adverse impact of previous ASCT – patients after ASCT did better in IRD than RD arm (PFS 23.0 vs 9.7 months).1
The subsequent subgroup analysis showed following results: There was only a limited number of patients with known high-risk cytogenetics (IRD 15, RD 19), still, with a trend to negative impact on PFS (7,3 and 9,9 months). Pretreatment with PIs did not significantly affect the outcomes. There was, however, negative impact of exposure to IMiDs in both IRD (PFS 11,3 months vs not reached) and RD arms (PFS 9,3 vs 18,0 months). Patients who were relapsed and refractory did worse to those who were relapsed only in both IRD (PFS 9,7 months vs not reached) and RD arms (PFS 6,0 vs 14,8 months).
Conclusion
Most of the subgroups that do not benefit with either treatment, correlate with either patient´s overall condition or the aggressiveness of the disease itself. Groups with worse outcomes were as follows: later relapse (≥4), higher age (≥75 years), the presence of high risk features – extramedullary disease, high-risk cytogenetics, higher stage (ISS 3) and refractory status in the previous line. We did not find an adverse impact of pretreatment by PIs or ASCT but patients with previous IMiDs had worse outcomes in both IRD and RD arms.
With support of AZV 17-29343A, NV18–03-00500, MH CZ – DRO (FNOl, 00098892), IGA-LF-2020-002.
1) Minarik J, Pika T, Radocha J. et al. Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice. BMC Cancer 2021; 21: https://doi.org/10.1186/s12885-020-07732-1
Keyword(s): Myeloma, Relapse, Therapy