Contributions
Abstract: PB1871
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) patients are at a significantly increased risk of developing a second malignant neoplasm. Recent introduction of B-cell receptor inhibitors (BCRi) ibrutinib and idelalisib was a major breakthrough in the treatment of relapsed and refractory disease. However, knowledge on incidence of second cancers in the context of BCRi therapy is limited.
Aims
To study the incidence and pattern of second cancers and Richter transformation (RT) in relapsed and refractory CLL patients treated with ibrutinib or idelalisib.
Methods
Retrospective analysis was performed concerning diagnosis and outcome of second malignancies occurring during BCRi treatment in Polish hematology centers of the Polish Adult Leukemia Study Group (PALG).
Results
Clinical data of 211 heavily pretreated relapsed and refractory CLL patients, of whom 157 received ibrutinib and 54 were treated with idelalisib, were included in the analysis. Median ibrutinib treatment duration was 33.5 (range 0.4 – 46.8) months. Eleven (7%) second malignancies developed under ibrutinib therapy including 7 cancers of epithelial origin (2 lung cancers, 2 skin cancers, 1 peritoneal cancer, 1 urinary bladder and 1 breast cancer) and 4 cases of RT (3 histologically confirmed Hodgkin variant of RT and 1 clinically suspected RT of unknown histology). Median time from CLL diagnosis to the diagnosis of second malignancy was 83.1 (38.3 – 298.0) months, while median time from ibrutinib initiation to second cancer reached 19.63 (3.9 – 31.9) months. Idelalisib alone or in combination with anti-CD20 antibodies was administered for a median of 13.8 (0.1 – 23.5) months. In the group of idelalisib treated patients 7 (12.9%) malignancies occurred including 5 epithelial cancers (2 thyroid cancers, 1 renal cancer, 1 penile cancer and 1 gastric cancer) and 2 RT. Median time from CLL diagnosis to second cancer and median time from idelalisib start to diagnosis of second cancer were 47.7 (13.1 – 178) months and 21.3 (2.3 – 31.5) months, respectively. Comparing the frequency of second malignancies in ibrutinib and idelalisib treated patients, we did not reveal significant differences between both cohorts (p=0.25). The analysis of clinical decisions following the diagnosis of second malignancies in this real-life patient population showed different strategies including transient or permanent discontinuation of BCRi or dose modifications. Regarding the outcome of patients with second cancer, 6 out of 11 patients in the ibrutinib cohort and 2 out of 5 patients treated with idelalisib died. Importantly, in all these cases the second malignancy was the primary cause of death.
Conclusion
In this retrospective analysis we show that second cancers are not an uncommon clinical problem during BCRi therapy of CLL, at least in relapsed refractory patients, heavily pretreated with standard alkylating agents and/or purine nucleoside analogs based therapies. Interestingly, we observed more epithelial cancers than RT. The potential influence of specific type of BCRi on incidence of second cancers as well as optimal dosing of BCRi during systemic treatment of second malignancies needs further research.
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical
Keyword(s): B-CLL, Second malignancy, Treatment
Abstract: PB1871
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) patients are at a significantly increased risk of developing a second malignant neoplasm. Recent introduction of B-cell receptor inhibitors (BCRi) ibrutinib and idelalisib was a major breakthrough in the treatment of relapsed and refractory disease. However, knowledge on incidence of second cancers in the context of BCRi therapy is limited.
Aims
To study the incidence and pattern of second cancers and Richter transformation (RT) in relapsed and refractory CLL patients treated with ibrutinib or idelalisib.
Methods
Retrospective analysis was performed concerning diagnosis and outcome of second malignancies occurring during BCRi treatment in Polish hematology centers of the Polish Adult Leukemia Study Group (PALG).
Results
Clinical data of 211 heavily pretreated relapsed and refractory CLL patients, of whom 157 received ibrutinib and 54 were treated with idelalisib, were included in the analysis. Median ibrutinib treatment duration was 33.5 (range 0.4 – 46.8) months. Eleven (7%) second malignancies developed under ibrutinib therapy including 7 cancers of epithelial origin (2 lung cancers, 2 skin cancers, 1 peritoneal cancer, 1 urinary bladder and 1 breast cancer) and 4 cases of RT (3 histologically confirmed Hodgkin variant of RT and 1 clinically suspected RT of unknown histology). Median time from CLL diagnosis to the diagnosis of second malignancy was 83.1 (38.3 – 298.0) months, while median time from ibrutinib initiation to second cancer reached 19.63 (3.9 – 31.9) months. Idelalisib alone or in combination with anti-CD20 antibodies was administered for a median of 13.8 (0.1 – 23.5) months. In the group of idelalisib treated patients 7 (12.9%) malignancies occurred including 5 epithelial cancers (2 thyroid cancers, 1 renal cancer, 1 penile cancer and 1 gastric cancer) and 2 RT. Median time from CLL diagnosis to second cancer and median time from idelalisib start to diagnosis of second cancer were 47.7 (13.1 – 178) months and 21.3 (2.3 – 31.5) months, respectively. Comparing the frequency of second malignancies in ibrutinib and idelalisib treated patients, we did not reveal significant differences between both cohorts (p=0.25). The analysis of clinical decisions following the diagnosis of second malignancies in this real-life patient population showed different strategies including transient or permanent discontinuation of BCRi or dose modifications. Regarding the outcome of patients with second cancer, 6 out of 11 patients in the ibrutinib cohort and 2 out of 5 patients treated with idelalisib died. Importantly, in all these cases the second malignancy was the primary cause of death.
Conclusion
In this retrospective analysis we show that second cancers are not an uncommon clinical problem during BCRi therapy of CLL, at least in relapsed refractory patients, heavily pretreated with standard alkylating agents and/or purine nucleoside analogs based therapies. Interestingly, we observed more epithelial cancers than RT. The potential influence of specific type of BCRi on incidence of second cancers as well as optimal dosing of BCRi during systemic treatment of second malignancies needs further research.
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical
Keyword(s): B-CLL, Second malignancy, Treatment