Contributions
Abstract: PB1649
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Carfilzomib, a second-generation proteasome inhibitor, in combination with lenalidomide plus dexamethasone (KRD) is approved for the treatment of patients with relapsed/refractory multiple mm (RRMM) after 1-3 prior lines.
Aims
Our objective was aimed to analyse the efficacy and safety of KRD in a real-life cohort in eleven hospitals from Catalonia.
Methods
A real-life retrospective analysis of RRMM patients treated with KRD at hospitals in GEMMAC group from January 2016 until May 2020. KRd was administrated at standard schedule (carfilzomib 27mg/m2, d1,2,8,9,15,16; lenalidomide 25mg/d,d1-21 (adjusted by renal clearance); dexamethasone 20-40mg,d1,8,15, 22). Response rate was assessed using IMWG criteria. Progression free survival (PFS) and overall survival (OS) were calculated from the start of KRD treatment using Kaplan-Meier method. Cytogenetic high-risk (HR) included t(4;14), t(14;16) or del(17p) vs. Standard risk (SR).
Results
We included 149 patients with a median age of 66 years (range:40-88); 56% were male. Forty-four (29%), 57(38%) and 42(28%) patients were ISS1, ISS2 and ISS3, respectively. Ninety-seven (65%) patients had cytogenetic information by FISH at diagnosis, thirty-six (37%) of them had HR cytogenetic. Median prior lines of therapy were 1 (range: 1-4), 120(80%) patients had received only one prior line. All patients had previously received bortezomib and 61(41%) thalidomide. Seventeen (11%) patients had been exposed to lenalidomide previously. The overall response rate (ORR) was 75% (53% ≥VGPR, 38% ≥CR) with a median time to best response of 4 months. Median time on treatment was 6 (1-46) months. One hundred one (68%) patients discontinued treatment, mainly due to progression and toxicity: 49 (33%) and 17(11%) patients, respectively. Twenty-one (14%) patients received consolidation with autologous transplantation (ASCT) and 7 (5%) patients with allogeneic transplantation (AlloSCT). After a median of 18 months of follow-up, median PFS and OS were 26 (95% CI, 20-33) and 42 (95% CI, 34-50) months, respectively. Median PFS and OS at 1st, 2nd and subsequent relapse were 28 (95%CI, 22-34), 22 (95%CI, 1-46) and 1 (95%CI,1-4) months (p=0,004) and 50 (95%CI, 30-70), 37 (95%CI, 0-79) and 4 (95%CI, 0-8) (p=0,014) months, respectively. PFS was shorter in HR cytogenetic group patients but did not achieve statistically significance (HR: 12 [95%CI, 1-27] months vs SR: 25 [95%CI, 15-34] months, p=0.15). OS was either not significantly different in this group (OS: HR: not reached vs SR: 50 months, p=0,15). Median PFS and OS in a subgroup of patients who consolidated with ASCT or AlloSCT (28 [19%]) were longer [PFS: not reached vs 20 (95%CI,9-31) months, p=0.001; OS: not reached vs 42 (95%CI,29-55) months, p=0.007]. The most common adverse effects (incidence >10%) were hematological [anemia (41%), leukopenia (36%) and thrombocytopenia (34%)], infection (32%), asthenia (25%), gastrointestinal (19%) and cutaneous (10%). Fifteen (10%) patients discontinued carfilzomib due to toxicity, 6 (4%) of them by cardiovascular toxicity.
Conclusion
Our cohort shows that KRD is especially effective (ORR: 82%) in patients at first or second relapses after bortezomib- or thalidomide-based regimen. In patients who were candidates for transplantation (ASCT or AlloSCT) KRD was an effective salvage treatment. The most frequent toxicities were haematological and infectious complications. Cardiac toxicity, even not frequent, was the main cause of carfilzomib discontinuation. In conclusion, this data shows that KRD is an effective and safe regimen in patients with RRMM.
Keyword(s): Hematological malignancy, Multiple myeloma, Proteasome inhibitor
Abstract: PB1649
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Carfilzomib, a second-generation proteasome inhibitor, in combination with lenalidomide plus dexamethasone (KRD) is approved for the treatment of patients with relapsed/refractory multiple mm (RRMM) after 1-3 prior lines.
Aims
Our objective was aimed to analyse the efficacy and safety of KRD in a real-life cohort in eleven hospitals from Catalonia.
Methods
A real-life retrospective analysis of RRMM patients treated with KRD at hospitals in GEMMAC group from January 2016 until May 2020. KRd was administrated at standard schedule (carfilzomib 27mg/m2, d1,2,8,9,15,16; lenalidomide 25mg/d,d1-21 (adjusted by renal clearance); dexamethasone 20-40mg,d1,8,15, 22). Response rate was assessed using IMWG criteria. Progression free survival (PFS) and overall survival (OS) were calculated from the start of KRD treatment using Kaplan-Meier method. Cytogenetic high-risk (HR) included t(4;14), t(14;16) or del(17p) vs. Standard risk (SR).
Results
We included 149 patients with a median age of 66 years (range:40-88); 56% were male. Forty-four (29%), 57(38%) and 42(28%) patients were ISS1, ISS2 and ISS3, respectively. Ninety-seven (65%) patients had cytogenetic information by FISH at diagnosis, thirty-six (37%) of them had HR cytogenetic. Median prior lines of therapy were 1 (range: 1-4), 120(80%) patients had received only one prior line. All patients had previously received bortezomib and 61(41%) thalidomide. Seventeen (11%) patients had been exposed to lenalidomide previously. The overall response rate (ORR) was 75% (53% ≥VGPR, 38% ≥CR) with a median time to best response of 4 months. Median time on treatment was 6 (1-46) months. One hundred one (68%) patients discontinued treatment, mainly due to progression and toxicity: 49 (33%) and 17(11%) patients, respectively. Twenty-one (14%) patients received consolidation with autologous transplantation (ASCT) and 7 (5%) patients with allogeneic transplantation (AlloSCT). After a median of 18 months of follow-up, median PFS and OS were 26 (95% CI, 20-33) and 42 (95% CI, 34-50) months, respectively. Median PFS and OS at 1st, 2nd and subsequent relapse were 28 (95%CI, 22-34), 22 (95%CI, 1-46) and 1 (95%CI,1-4) months (p=0,004) and 50 (95%CI, 30-70), 37 (95%CI, 0-79) and 4 (95%CI, 0-8) (p=0,014) months, respectively. PFS was shorter in HR cytogenetic group patients but did not achieve statistically significance (HR: 12 [95%CI, 1-27] months vs SR: 25 [95%CI, 15-34] months, p=0.15). OS was either not significantly different in this group (OS: HR: not reached vs SR: 50 months, p=0,15). Median PFS and OS in a subgroup of patients who consolidated with ASCT or AlloSCT (28 [19%]) were longer [PFS: not reached vs 20 (95%CI,9-31) months, p=0.001; OS: not reached vs 42 (95%CI,29-55) months, p=0.007]. The most common adverse effects (incidence >10%) were hematological [anemia (41%), leukopenia (36%) and thrombocytopenia (34%)], infection (32%), asthenia (25%), gastrointestinal (19%) and cutaneous (10%). Fifteen (10%) patients discontinued carfilzomib due to toxicity, 6 (4%) of them by cardiovascular toxicity.
Conclusion
Our cohort shows that KRD is especially effective (ORR: 82%) in patients at first or second relapses after bortezomib- or thalidomide-based regimen. In patients who were candidates for transplantation (ASCT or AlloSCT) KRD was an effective salvage treatment. The most frequent toxicities were haematological and infectious complications. Cardiac toxicity, even not frequent, was the main cause of carfilzomib discontinuation. In conclusion, this data shows that KRD is an effective and safe regimen in patients with RRMM.
Keyword(s): Hematological malignancy, Multiple myeloma, Proteasome inhibitor