Contributions
Abstract: PB2227
Type: Publication Only
Background
Based on the TOURMALINE-MM1 trial, Ixazomib (Ixa) is a novel oral proteasome inhibitor (PI), which in combination with lenalidomide and dexamethasone (IxaRD) prolongs progression free survival and increases the overall response rate over RD alone.
Aims
To evaluate the efficacy and safety of IxaRd in the real-world clinical practice in Slovenia.
Methods
We retrospectivelly analysed data on heavily pretreated patients with RRMM, treated with IxaRD regimen from July 2016 to January 2018, that were included in the compassionate ixazomib use Named-Patient Program in Slovenia. We compared our data with significantly less pretreated patients in Tourmaline MM1 study. Primary end point was overall response rate (ORR). Secondary endpoints included duration of treatment, number of patients experiencing adverse effects (AE) and treatment discontinuation reasons.
Results
We treated 47 patients; Female/Male ratio was 30%/70%, median age at enrollment was 68 (46-82), median age at diagnosis 62, ISS I or II 59% and ISS III 41%. They were previously treated with median 5 (1-11) lines of therapy. 94% of patients were previously treated with bortezomib based regimens, 11% were primarily refractory. 69% of patients received lenalidomide based regimen (24% were refractory), and 13% received pomalidomide. At diagnosis, cytogenetics was not assessed in 47% (22/47) of patients: 15% (7/47) had high risk cytogenetics, 23% (11/47) intermediate risk and 15% (7/47) standard risk. Translocation (4;14) and gaining of (1q21) were determined as intermediate risk. 45 patients (96%) were treated with the IxaRD combination, 5 of those (10%) have continued without lenalidomide due to side effects. Two patients (4%) started treatment with ixazomib-dexamethasone regimen. Median number of cycles administered was 4,5 and 12 patients are still receiving treatment. Response rate was assesed according to IMWG criteria. ORR in these patients was 33%; 5 patients (10%) achieved CR, 5 (10%) VGPR, 6 (13%) PR. In addition we observed minimal response or at least stable disease in 17% of patients. In 27% of patients disease progressed. In 23% of patients we were not able to evaluate the response rate due to the short period of treatment. In 5 patients refractory to bortezomib, 1 VGPR and 1PR were observed. There were no AE reported amog 62% of patients. 6% of patients had polyneuropathy, 16% had cytopenias, 2% dizziness , 4% infection, 2% generalized skin rash, and 2% acute renal impairment, leading to treatment discontinuation in 8 patients.
Conclusion
The dataset from this real life study describes results of IxaRD regimen in our heavily pretreated and high risk patients. It also emphasises the difference between real life data and clinical trials. Namely our patients received many more lines of therapy and had more often unfavorable disease markers. The overal response rate, including MR and SD patients, was 50%, which is significantly less than the ORR published in Tourmaline study (78%). Clinical benefit rate was much lower in patients treated beyond 5th treatment line, including bortezomib and lenalidomide refractory patietns. We noticed that resistance to bortezomib doesn't always mean, that the patient is ixazomib resistant too; 40% of bortezomib refractory pts responded to ixazomib. It would be interesting to find out how it is with cross resistance interactions between karfilzomib and ixazomib and vice versa. During the observational period there were no ixazomib related deaths. IxaRd appears to be a reasonablly safe and effective treatment option.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Clinical data, Myeloma, Proteasome inhibitor
Abstract: PB2227
Type: Publication Only
Background
Based on the TOURMALINE-MM1 trial, Ixazomib (Ixa) is a novel oral proteasome inhibitor (PI), which in combination with lenalidomide and dexamethasone (IxaRD) prolongs progression free survival and increases the overall response rate over RD alone.
Aims
To evaluate the efficacy and safety of IxaRd in the real-world clinical practice in Slovenia.
Methods
We retrospectivelly analysed data on heavily pretreated patients with RRMM, treated with IxaRD regimen from July 2016 to January 2018, that were included in the compassionate ixazomib use Named-Patient Program in Slovenia. We compared our data with significantly less pretreated patients in Tourmaline MM1 study. Primary end point was overall response rate (ORR). Secondary endpoints included duration of treatment, number of patients experiencing adverse effects (AE) and treatment discontinuation reasons.
Results
We treated 47 patients; Female/Male ratio was 30%/70%, median age at enrollment was 68 (46-82), median age at diagnosis 62, ISS I or II 59% and ISS III 41%. They were previously treated with median 5 (1-11) lines of therapy. 94% of patients were previously treated with bortezomib based regimens, 11% were primarily refractory. 69% of patients received lenalidomide based regimen (24% were refractory), and 13% received pomalidomide. At diagnosis, cytogenetics was not assessed in 47% (22/47) of patients: 15% (7/47) had high risk cytogenetics, 23% (11/47) intermediate risk and 15% (7/47) standard risk. Translocation (4;14) and gaining of (1q21) were determined as intermediate risk. 45 patients (96%) were treated with the IxaRD combination, 5 of those (10%) have continued without lenalidomide due to side effects. Two patients (4%) started treatment with ixazomib-dexamethasone regimen. Median number of cycles administered was 4,5 and 12 patients are still receiving treatment. Response rate was assesed according to IMWG criteria. ORR in these patients was 33%; 5 patients (10%) achieved CR, 5 (10%) VGPR, 6 (13%) PR. In addition we observed minimal response or at least stable disease in 17% of patients. In 27% of patients disease progressed. In 23% of patients we were not able to evaluate the response rate due to the short period of treatment. In 5 patients refractory to bortezomib, 1 VGPR and 1PR were observed. There were no AE reported amog 62% of patients. 6% of patients had polyneuropathy, 16% had cytopenias, 2% dizziness , 4% infection, 2% generalized skin rash, and 2% acute renal impairment, leading to treatment discontinuation in 8 patients.
Conclusion
The dataset from this real life study describes results of IxaRD regimen in our heavily pretreated and high risk patients. It also emphasises the difference between real life data and clinical trials. Namely our patients received many more lines of therapy and had more often unfavorable disease markers. The overal response rate, including MR and SD patients, was 50%, which is significantly less than the ORR published in Tourmaline study (78%). Clinical benefit rate was much lower in patients treated beyond 5th treatment line, including bortezomib and lenalidomide refractory patietns. We noticed that resistance to bortezomib doesn't always mean, that the patient is ixazomib resistant too; 40% of bortezomib refractory pts responded to ixazomib. It would be interesting to find out how it is with cross resistance interactions between karfilzomib and ixazomib and vice versa. During the observational period there were no ixazomib related deaths. IxaRd appears to be a reasonablly safe and effective treatment option.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Clinical data, Myeloma, Proteasome inhibitor