Contributions
Abstract: PB2208
Type: Publication Only
Background
Therapeutic advances, notably the development of regimens that incorporate immune-modulatory drugs (lenalidomide and pomalidomide) and proteasome inhibitors (e.g. bortezomib and carfilzomib), have improved survival outcome in multiple myeloma (MM). However, MM remains largely incurable and patients invariable develop relapsed or refractory (R/R) disease, a new unmet clinical challenge for hematologists. Relapse can be characterized according to disease aggressiveness and the presence of clinical symptoms. Aggressive disease relapse can occur at biochemical level, due to rapid and relevant increase of monoclonal component or LDH, or at clinical level it can be defined by the presence of extramedullary disease, acute renal injury or progression to secondary plasma cell leukemia.
Aims
In this retrospective study we evaluated 76 patients who relapsed after a front-line regimen containing lenalidomide or bortezomib to identify the rate of biochemical and clinical aggressive relapses and clinical outcome upon treatment with second generation novel agents (pomalidomide and carfilzomib).
Methods
From July 2014 we evaluated 76 R/R patients (41 males and 35 females, median age 62 years, range 45-78). Median number of previous line was 3 (1-6), half of them (43/76) underwent ASCT. Pd consisted of pomalidomide 4 mg daily given orally on Days 1–21 of each 28-day cycle and dexamethasone 40 mg weekly. KRd consisted of Carfilzomib 20 mg/m2 IV on days 1 and 2 of the first cycle, then 27 mg/m2 on days 8, 9, 15 16 of the first cycle and days 1, 2, 8, 9, 15 and 16 of the subsequent cycles, Dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16 and lenalidomide 25 mg daily given orally on days 1–21 of each 28-day cycle.
Results
51 patients were both bortezomib and/or lenalidomide refractory and received Pd according to Italian Health System. 7 of them further progressed and received KRd, the remain 25 received KRd as second and third line therapy. 53 patients had a non aggressive relapse, while the remain 23 experienced an aggressive relapse of disease. 43 patients experiencing relapse after ASCT, 44% had asymptomatic serological relapse or progression, 66% experienced symptomatic relapse (with 38% high risk cytogenetic detected by FISH) and one-third experienced relapse featuring extramedullary disease, plasma cell leukemia or severe renal failure. In the remaining 33 patients not eligible to ASCT, 78% had not aggressive relapse. As expected median PFS obtained in Pd patients was higher for NA group (6 vs 4 months). Even if the majority of KRd patients are still under treatment, the OR was 90% with greater PFS in NA than in A group (8 vs 6 months).
Conclusion
In our community setting data, heavily pretreated patients achieved improvement of outcome obtaining a median PFS >4 months, using KRd and Pd as salvage therapies. We found that an aggressive relapse was more frequent in young patients and that earlier treatment at biochemical asymptomatic relapse is associated to better outcome.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): immunomodulation, Multiple Myeloma, Proteasome inhibitor
Abstract: PB2208
Type: Publication Only
Background
Therapeutic advances, notably the development of regimens that incorporate immune-modulatory drugs (lenalidomide and pomalidomide) and proteasome inhibitors (e.g. bortezomib and carfilzomib), have improved survival outcome in multiple myeloma (MM). However, MM remains largely incurable and patients invariable develop relapsed or refractory (R/R) disease, a new unmet clinical challenge for hematologists. Relapse can be characterized according to disease aggressiveness and the presence of clinical symptoms. Aggressive disease relapse can occur at biochemical level, due to rapid and relevant increase of monoclonal component or LDH, or at clinical level it can be defined by the presence of extramedullary disease, acute renal injury or progression to secondary plasma cell leukemia.
Aims
In this retrospective study we evaluated 76 patients who relapsed after a front-line regimen containing lenalidomide or bortezomib to identify the rate of biochemical and clinical aggressive relapses and clinical outcome upon treatment with second generation novel agents (pomalidomide and carfilzomib).
Methods
From July 2014 we evaluated 76 R/R patients (41 males and 35 females, median age 62 years, range 45-78). Median number of previous line was 3 (1-6), half of them (43/76) underwent ASCT. Pd consisted of pomalidomide 4 mg daily given orally on Days 1–21 of each 28-day cycle and dexamethasone 40 mg weekly. KRd consisted of Carfilzomib 20 mg/m2 IV on days 1 and 2 of the first cycle, then 27 mg/m2 on days 8, 9, 15 16 of the first cycle and days 1, 2, 8, 9, 15 and 16 of the subsequent cycles, Dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16 and lenalidomide 25 mg daily given orally on days 1–21 of each 28-day cycle.
Results
51 patients were both bortezomib and/or lenalidomide refractory and received Pd according to Italian Health System. 7 of them further progressed and received KRd, the remain 25 received KRd as second and third line therapy. 53 patients had a non aggressive relapse, while the remain 23 experienced an aggressive relapse of disease. 43 patients experiencing relapse after ASCT, 44% had asymptomatic serological relapse or progression, 66% experienced symptomatic relapse (with 38% high risk cytogenetic detected by FISH) and one-third experienced relapse featuring extramedullary disease, plasma cell leukemia or severe renal failure. In the remaining 33 patients not eligible to ASCT, 78% had not aggressive relapse. As expected median PFS obtained in Pd patients was higher for NA group (6 vs 4 months). Even if the majority of KRd patients are still under treatment, the OR was 90% with greater PFS in NA than in A group (8 vs 6 months).
Conclusion
In our community setting data, heavily pretreated patients achieved improvement of outcome obtaining a median PFS >4 months, using KRd and Pd as salvage therapies. We found that an aggressive relapse was more frequent in young patients and that earlier treatment at biochemical asymptomatic relapse is associated to better outcome.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): immunomodulation, Multiple Myeloma, Proteasome inhibitor