Contributions
Abstract: PB1500
Type: Publication Only
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
Treatment of chronic lymphocytic leukemia remains a significant challenge in gematology. Despite the large number of innovative targeted drugs used, the FCR program is used in many randomized trials as a reference for comparison, which indicates its importance not only for scientific tasks, but also for modern clinical practice, as it remains one of the most accessible. To date, the FCR program is included in the modern algorithm of the 1st line treatment of patients with CLL younger than 65 years with intact TP53, regardless of the mutated IGHV genes. This is based on data from randomized trials of the GCLLSG. In the CLL8 study, the standard FCR-program cycle was 28 days. There are not enough studies proving the efficacy of such treatment in patients with high comorbidity.
Aims
The aim of the study was to investigate the clinical efficacy of front-line FCR program treatment in CLL patients within a clinical model integrated into real practice.
Methods
The study included 108 previously untreated patients with CD20-positive chronic lymphocytic leukemia. The stage of the disease was assessed according to the Rai classification, the functional state was determined on the ECOG scale, and the comorbidity was assessed on the SIRS - G scale. The 17p13/TP53 deletion was calculated using the FISH method, and the IGHV-status observed through PCR. The FCR program consisting of 6 standard courses was being conducted over a longer period of time, which extended the induction period and reduced treatment density. Minimal residual disease (MRD) was assessed according to the international standardized protocol (Rawstron, 2007) by 4-color flow cytometry. Some patients were receiving maintenance treatment with Rituximab for 2 years, compared to the group of patients without maintenance therapy. The main control points of the analysis were PFS and OS. The OS was evaluated according to the intent-to-treat principle.
Results
The Me of the comorbidity index was 5(0-12). The Me of creatinine clearance was 60.4 ml / min (43-121). We have introduced the concept of treatment density (the ratio of the duration of the standard cycle to the original one) in real clinical practice. The drug doses were not reduced in our study. The Me of the FCR cycle in our study was 50 days. Accordingly, the Me duration of the induction treatment period increased to 9 months, and the treatment density decreased to 0.6. The clinical efficacy of the treatment was evaluated according to the iWCLL 2008. The overall respons rate was 92.6%, complete remission (CR) was detected in 53.9% patients. 52.8% patients had undetectable MRD (UMRD) in the peripheral blood and 39.3% patients had UMRD in the bone marrow. The Me follow-up was of 51 months (range 8-150). The Me of PFS from the beginning of FCR induction was 42 months. PFS was significantly longer in patients who achieved CR (p=0,0001), with comorbidity in patients below 5 index (p=0,02), and with achievement of UMRD (p=0,002). Reduced treatment density and maintenance therapy with Rituximab did not affect the duration of PFS. OS from the beginning of FCR-induction was 120 months in 60% of patients.
Conclusion
The study showed that the decrease in the density of the FCR program induction in real clinical practice in patients with CLL was accompanied by high efficacy and did not lead to a significant decrease in the PFS compared to patients who received the standard program.
Keyword(s): Chronic lymphocytic leukemia, MRD, Practice
Abstract: PB1500
Type: Publication Only
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
Treatment of chronic lymphocytic leukemia remains a significant challenge in gematology. Despite the large number of innovative targeted drugs used, the FCR program is used in many randomized trials as a reference for comparison, which indicates its importance not only for scientific tasks, but also for modern clinical practice, as it remains one of the most accessible. To date, the FCR program is included in the modern algorithm of the 1st line treatment of patients with CLL younger than 65 years with intact TP53, regardless of the mutated IGHV genes. This is based on data from randomized trials of the GCLLSG. In the CLL8 study, the standard FCR-program cycle was 28 days. There are not enough studies proving the efficacy of such treatment in patients with high comorbidity.
Aims
The aim of the study was to investigate the clinical efficacy of front-line FCR program treatment in CLL patients within a clinical model integrated into real practice.
Methods
The study included 108 previously untreated patients with CD20-positive chronic lymphocytic leukemia. The stage of the disease was assessed according to the Rai classification, the functional state was determined on the ECOG scale, and the comorbidity was assessed on the SIRS - G scale. The 17p13/TP53 deletion was calculated using the FISH method, and the IGHV-status observed through PCR. The FCR program consisting of 6 standard courses was being conducted over a longer period of time, which extended the induction period and reduced treatment density. Minimal residual disease (MRD) was assessed according to the international standardized protocol (Rawstron, 2007) by 4-color flow cytometry. Some patients were receiving maintenance treatment with Rituximab for 2 years, compared to the group of patients without maintenance therapy. The main control points of the analysis were PFS and OS. The OS was evaluated according to the intent-to-treat principle.
Results
The Me of the comorbidity index was 5(0-12). The Me of creatinine clearance was 60.4 ml / min (43-121). We have introduced the concept of treatment density (the ratio of the duration of the standard cycle to the original one) in real clinical practice. The drug doses were not reduced in our study. The Me of the FCR cycle in our study was 50 days. Accordingly, the Me duration of the induction treatment period increased to 9 months, and the treatment density decreased to 0.6. The clinical efficacy of the treatment was evaluated according to the iWCLL 2008. The overall respons rate was 92.6%, complete remission (CR) was detected in 53.9% patients. 52.8% patients had undetectable MRD (UMRD) in the peripheral blood and 39.3% patients had UMRD in the bone marrow. The Me follow-up was of 51 months (range 8-150). The Me of PFS from the beginning of FCR induction was 42 months. PFS was significantly longer in patients who achieved CR (p=0,0001), with comorbidity in patients below 5 index (p=0,02), and with achievement of UMRD (p=0,002). Reduced treatment density and maintenance therapy with Rituximab did not affect the duration of PFS. OS from the beginning of FCR-induction was 120 months in 60% of patients.
Conclusion
The study showed that the decrease in the density of the FCR program induction in real clinical practice in patients with CLL was accompanied by high efficacy and did not lead to a significant decrease in the PFS compared to patients who received the standard program.
Keyword(s): Chronic lymphocytic leukemia, MRD, Practice