Contributions
Abstract: EP631
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
Other malignancies occurring in patients with CLL are a well-known, but insufficiently investigated area, highlighting the need for further research.
Aims
To leverage the understanding of other malignancies in CLL, particularly regarding potential links to chemoimmunotherapy (CIT) and/or novel agents, as well as associations with relevant clinicobiological factors.
Methods
Data from consecutive sets of patients diagnosed with CLL between 2000-2016 were collected by affiliated members through ERIC and subjected to detailed statistical analysis. Collected variables included: demographics, stage at diagnosis, treatment, treatment response, death, cause of death, other malignancy (type, date of diagnosis, outcome), biomarker profiles.
Results
Overall, 13,808 patients from 64 centers were evaluated: 8,517 males, 5,291 females; median age: 66 (range, 27-92). At diagnosis, 74/16/10% of cases were classified as Binet stages A/B/C. Biomarker profiling (performed before frontline treatment): 1,055/6,310 cases (14.1%) with del(11q); 843/6,928 cases (10.8%) with TP53 aberrations [del(17p) and/or TP53 mutation]; 3,127 (48%) and 3,390 (52%) cases with unmutated or mutated IGHV genes, respectively. With a median follow-up of 77 months (range, 49-199), 7,134/13,308 (53.6%) patients had received ≥1 line(s) of treatment (1: 59.3%, 2: 19.3%, 3: 11%, 4+: 10.4%). Therapies received (at any line) included only CIT/CIT+novel agents/only novel agents in 71.5/21.3/7.2% of cases, respectively. Frontline therapies were FCR (32.3% of cases), bendamustine+/-antiCD20 (10.7%), other CIT (mostly chlorambucil+antiCD20) (46.7%), BTKi+/-combinations (4.8%), idelalisib+/-combinations (0.5%), venetoclax+/-combinations (0.9%), various other regimens (4%). Within this series, 2,919/13,808 cases (21.1%) were reported with other malignancies besides CLL; cases with Richter’s transformation (n=390/10,157, 3.8%) were not included in this count. CLL diagnosis preceded the other malignancy in 1,939 cases (14% of the cohort): of these, 317 and 1,622 cases developed other hematological or non-hematological malignant neoplasms, respectively. The great majority of the former concerned MDS/AML (31%) and other lymphoid malignancies (49%), excluding MGUS. The incidence of MDS/AML was significantly enriched in (i) patients with unmutated IGHV genes (p=0.05) or del(11q) (p=0.009); (ii) treated patients (p<0.001), particularly those receiving ≥3 treatment lines (p<0.01); and (iii) patients treated with FCR (p<0.001). FCR retained independence on multivariate analysis. Within the group of non-hematological malignant neoplasms, non-melanoma skin cancer (NMSC) accounted for 31% of cases; malignant neoplasms of the prostate, colon, breast, bronchus/lung and melanoma collectively accounted for 41.6% of cases. Several of these neoplasms were significantly more prevalent in untreated patients (p<0.01 for breast, prostate, colon), despite that the follow-up of treated vs untreated patients did not differ significantly. Only NMSC was significantly more prevalent (p=0.007) in treated patients.
Conclusion
We report strong associations between the development of other hematological malignancies, especially MDS/AML, and certain biological features as well as treatment for CLL, with a highly relevant risk for patients treated with CIT, particularly the FCR regimen. In contrast, the development of solid tumors appeared unaffected by treatment administration, prompting further investigation in specific patient subgroups that will be presented at the congress.
Keyword(s): Chronic lymphocytic leukemia
Abstract: EP631
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
Other malignancies occurring in patients with CLL are a well-known, but insufficiently investigated area, highlighting the need for further research.
Aims
To leverage the understanding of other malignancies in CLL, particularly regarding potential links to chemoimmunotherapy (CIT) and/or novel agents, as well as associations with relevant clinicobiological factors.
Methods
Data from consecutive sets of patients diagnosed with CLL between 2000-2016 were collected by affiliated members through ERIC and subjected to detailed statistical analysis. Collected variables included: demographics, stage at diagnosis, treatment, treatment response, death, cause of death, other malignancy (type, date of diagnosis, outcome), biomarker profiles.
Results
Overall, 13,808 patients from 64 centers were evaluated: 8,517 males, 5,291 females; median age: 66 (range, 27-92). At diagnosis, 74/16/10% of cases were classified as Binet stages A/B/C. Biomarker profiling (performed before frontline treatment): 1,055/6,310 cases (14.1%) with del(11q); 843/6,928 cases (10.8%) with TP53 aberrations [del(17p) and/or TP53 mutation]; 3,127 (48%) and 3,390 (52%) cases with unmutated or mutated IGHV genes, respectively. With a median follow-up of 77 months (range, 49-199), 7,134/13,308 (53.6%) patients had received ≥1 line(s) of treatment (1: 59.3%, 2: 19.3%, 3: 11%, 4+: 10.4%). Therapies received (at any line) included only CIT/CIT+novel agents/only novel agents in 71.5/21.3/7.2% of cases, respectively. Frontline therapies were FCR (32.3% of cases), bendamustine+/-antiCD20 (10.7%), other CIT (mostly chlorambucil+antiCD20) (46.7%), BTKi+/-combinations (4.8%), idelalisib+/-combinations (0.5%), venetoclax+/-combinations (0.9%), various other regimens (4%). Within this series, 2,919/13,808 cases (21.1%) were reported with other malignancies besides CLL; cases with Richter’s transformation (n=390/10,157, 3.8%) were not included in this count. CLL diagnosis preceded the other malignancy in 1,939 cases (14% of the cohort): of these, 317 and 1,622 cases developed other hematological or non-hematological malignant neoplasms, respectively. The great majority of the former concerned MDS/AML (31%) and other lymphoid malignancies (49%), excluding MGUS. The incidence of MDS/AML was significantly enriched in (i) patients with unmutated IGHV genes (p=0.05) or del(11q) (p=0.009); (ii) treated patients (p<0.001), particularly those receiving ≥3 treatment lines (p<0.01); and (iii) patients treated with FCR (p<0.001). FCR retained independence on multivariate analysis. Within the group of non-hematological malignant neoplasms, non-melanoma skin cancer (NMSC) accounted for 31% of cases; malignant neoplasms of the prostate, colon, breast, bronchus/lung and melanoma collectively accounted for 41.6% of cases. Several of these neoplasms were significantly more prevalent in untreated patients (p<0.01 for breast, prostate, colon), despite that the follow-up of treated vs untreated patients did not differ significantly. Only NMSC was significantly more prevalent (p=0.007) in treated patients.
Conclusion
We report strong associations between the development of other hematological malignancies, especially MDS/AML, and certain biological features as well as treatment for CLL, with a highly relevant risk for patients treated with CIT, particularly the FCR regimen. In contrast, the development of solid tumors appeared unaffected by treatment administration, prompting further investigation in specific patient subgroups that will be presented at the congress.
Keyword(s): Chronic lymphocytic leukemia