OTHER MALIGNANCIES IN THE HISTORY OF CHRONIC LYMPHOCYTIC LEUKEMIA – A RETROSPECTIVE, MULTICENTER COHORT STUDY BY ERIC, THE EUROPEAN RESEARCH INITIATIVE ON CLL, IN HARMONY
Author(s): ,
Thomas Chatzikonstantinou
Affiliations:
European Research Initiative on CLL,Barcelona,Spain;INAB, CERTH,Thessaloniki,Greece
,
Lydia Scarfò
Affiliations:
Università Vita Salute and IRCCS Ospedale San Raffaele,Milan,Italy;European Research Initiative on CLL,Barcelona,Spain
,
Jana Kotašková
Affiliations:
Department of Internal Medicine - Hematology and Oncology,University Hospital Brno,Brno,Czech Republic;CEITEC,Masaryk University,Brno,Czech Republic
,
Gloria Iacoboni
Affiliations:
Vall d'Hebron University Hospital,Barcelona,Spain
,
Evangelia Minga
Affiliations:
INAB, CERTH,Thessaloniki,Greece
,
Dimitra Chammou
Affiliations:
INAB, CERTH,Thessaloniki,Greece
,
George Karakatsoulis
Affiliations:
INAB, CERTH,Thessaloniki,Greece
,
Miguel Alcoceba
Affiliations:
University Hospital of Salamanca (HUS/IBSAL), CIBERONC and Cancer Research Institute of Salamanca-IBMCC (USAL-CSIC),Salamanca,Spain
,
Shaimaa El-Ashwah
Affiliations:
Clinical Hematology Unit, Oncology Center, Medical Faculty,Mansoura University,Mansoura,Egypt
,
Francesca Bacchiarri
Affiliations:
Hematology,University of Siena, AOUS,Siena,Italy
,
Mehreen Ali Khan
Affiliations:
AFBMTC/NIBMT,Rawalpindi,Pakistan
,
Ramona Cassin
Affiliations:
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano,Milan,Italy
,
Sophia Chatzileontiadou
Affiliations:
Hematology Unit, 1st Dept of Internal Medicine, AUTH, AHEPA Hospital,Thessaloniki,Greece
,
Amy Christian
Affiliations:
Royal Bournemouth Hospital,Bournemouth,United Kingdom
,
Rosa Collado
Affiliations:
Hospital General Universitario Valencia,Valencia,Spain
,
Marcos Daniel De Deus Santos
Affiliations:
Universidades Federal do Espirito Santo,Vitória,Brazil
,
Zadie Davis
Affiliations:
Royal Bournemouth Hospital,Bournemouth,United Kingdom
,
Christos Demosthenous
Affiliations:
Hematology Department and HCT Unit, G. Papanicolaou Hospital,Thessaloniki,Greece
,
Maria Dimou
Affiliations:
1st Internal Medicine Department, Propaedeutic, Hematology Clinical Trial Unit, National and Kapodistrian University of Athens,Athens,Greece
,
David Donaldson
Affiliations:
Haematology Department,Belfast City Hospital,Belfast,United Kingdom
,
Gimena Dos Santos
Affiliations:
Hospital de Clínicas Dr. Manuel Quintela,Montevideo,Uruguay
,
Barbara Dreta
Affiliations:
University Hospital Center,Zagreb,Croatia
,
Maria Efstathopoulou
Affiliations:
Iatriko Medical Center,Athens,Greece
,
Alicia Enrico
Affiliations:
Hospital Italiano La Plata,Buenos Aires,Argentina
,
Alberto Fresa
Affiliations:
Hematology Unit, Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology,Fondazione Policlinico Universitario A. Gemelli IRCCS,Roma,Italy
,
Sara Galimberti
Affiliations:
Ospedale Santa Chiara,Pisa,Italy
,
Rocío García-Serra
Affiliations:
Hospital General Universitario Valencia,Valencia,Spain
,
Isabel González-Gascón-y-Marín
Affiliations:
Hospital  Infanta Leonor,Madrid,Spain
,
Alessandro Gozzetti
Affiliations:
Hematology,University of Siena, AOUS,Siena,Italy
,
Valerio Guarente
Affiliations:
Centro di Ricerche Emato-Oncologiche,Perugia,Italy
,
Sean Harrop
Affiliations:
Peter Maccallum Cancer Center,Melbourne,Australia
,
Eleftheria Hatzimichael
Affiliations:
Department of Haematology, Faculty of Medicine, University of Ioannina,Ioannina,Greece
,
Yair Herishanu
Affiliations:
Department of Hematology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University,Tel Aviv,Israel
,
Michalis Iskas
Affiliations:
Hematology Department and HCT Unit, G. Papanicolaou Hospital,Thessaloniki,Greece
,
Ozren Jaksic
Affiliations:
Department of Hematology Dubrava University Hospital,Zagreb,Croatia
,
Susanne R. Janssen
Affiliations:
Amsterdam Medical Center,Amsterdam,Netherlands
,
Elżbieta Kalicińska
Affiliations:
Department of Hematology,Wroclaw Medical University,Wroclaw,Poland
,
Volkan Karakus
Affiliations:
Alanya Alaaddin Keykubat University Hospital, Alanya,Turkey
,
Arnon P. Kater
Affiliations:
Amsterdam Medical Center,Amsterdam,Netherlands
,
Bonnie Kho
Affiliations:
Pamela Youde Nethersole Eastern Hospital, Chai Wan,Hong Kong,Hong Kong
,
Εliana Konstantinou
Affiliations:
Haematology,University of Athens, Laikon General Hospital,Athens,Greece
,
Maya Koren-Michowitz
Affiliations:
Shamir Medical Center,Zerifin,Israel;Tel Aviv University,Tel Aviv,Israel
,
Ioannis Kotsianidis
Affiliations:
University Hospital of Alexandroupolis,Alexandroupolis,Greece
,
Robert J. Kreitman
Affiliations:
Laboratory of Molecular Biology, NCI, NIH,Bethesda,United States
,
Uttam Kumar Nath
Affiliations:
Department of Medical Oncology,All India Institute of Medical Sciences,Rishikesh,India
,
Jorge Labrador
Affiliations:
Complejo Asistencial Universitario de Burgos,Burgos,Spain
,
Deepesh P. Lad
Affiliations:
Department of Internal Medicine,Post Graduate Institute of Medical Education and Research,Chandigarh,India
,
Mark-David Levin
Affiliations:
Albert Schweitzer Hospital,Dordrecht,Netherlands
,
Ilana Levy
Affiliations:
Bnai Zion Medical center,Haifa,Israel
,
Alberto Lopez-Garcia
Affiliations:
Fundacion Jimenez Diaz University Hospital,Madrid,Spain
,
Juan Marquet
Affiliations:
Ramon y Cajal University Hospital,Madrid,Spain
,
Stanislava Mašlejová
Affiliations:
Department of Internal Medicine - Hematology and Oncology,University Hospital Brno,Brno,Czech Republic
,
Carlota Mayor-Bastida
Affiliations:
La Princesa University Hospital,Madrid,Spain
,
Biljana Mihaljevic
Affiliations:
Clinical Center of Serbia,Belgrade,Serbia;University of Belgrade,Belgrade,Serbia
,
Ivana Milosevic
Affiliations:
Faculty of Medicine,University of Novi Sad,Novi Sad,Serbia
,
Fatima Miras
Affiliations:
12 de Octubre University Hospital,Madrid,Spain
,
Riccardo Moia
Affiliations:
University of Eastern Piedmont,Novara,Italy
,
Marta Morawska
Affiliations:
Hematology Department,St. John's Cancer Center,Lublin,Poland;Experimental Hematooncology Department,Medical University of Lublin,Lublin,Poland
,
Almudena Navarro-Bailón
Affiliations:
University Hospital of Salamanca (HUS/IBSAL), CIBERONC and Cancer Research Institute of Salamanca-IBMCC (USAL-CSIC),Salamanca,Spain
,
David Oscier
Affiliations:
Royal Bournemouth Hospital,Bournemouth,United Kingdom
,
Ana C. Oliveira
Affiliations:
ICO Hospitalet, IDIBELL,Barcelona,Spain
,
Jacopo Olivieri
Affiliations:
Hematology Clinic,Azienda Sanitaria Universitaria Friuli Centrale,Udine,Italy
,
Tomáš Papajík
Affiliations:
Department of Haemato-Oncology,University Hospital Olomouc,Olomouc,Czech Republic
,
Maria Papaioannou
Affiliations:
Hematology Unit, 1st Dept of Internal Medicine, AUTH, AHEPA Hospital,Thessaloniki,Greece
,
Cheyenne Pierie
Affiliations:
Amsterdam Medical Center,Amsterdam,Netherlands
,
Anna Puiggros
Affiliations:
Pathology and Hematology Services, Hospital del Mar,Barcelona,Spain
,
Gianluigi Reda
Affiliations:
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano,Milan,Italy
,
Gian Matteo Rigolin
Affiliations:
Hematology Unit,St. Anna University Hospital,Ferrara,Italy
,
Rosa Ruchlemer
Affiliations:
Shaare Zedek Medical Center,Jerusalem,Israel
,
Gokmen Sevindik
Affiliations:
Medipol Universiy Hospital,İstanbul,Turkey
,
Salem Al-Shemari
Affiliations:
Kuwait University,Kuwait City,Kuwait
,
Yandong Shen
Affiliations:
Royal North Shore Hospital and University of Sydney,Sydney,Australia
,
Martin Šimkovič
Affiliations:
4th Department of Internal Medicine - Hematology,University Hospital Hradec Králové and Charles University Faculty of Medicine,Hradec Králové,Czech Republic
,
Svetlana Smirnova
Affiliations:
National Research Center for Hematology,Moscow,Russian Federation
,
Dina Sameh Abdelrahman Soliman
Affiliations:
Department of Laboratory Medicine & Pathology,Hamad Medical Corporation,Doha,Qatar
,
Martin Špaček
Affiliations:
1st Department of Medicine – Department of Hematology, First Faculty of Medicine,Charles University and General Hospital in Prague,Prague,Czech Republic
,
Tamar Tadmor
Affiliations:
Bnai Zion Medical center,Haifa,Israel
,
Liat Tourjeman
Affiliations:
Shaare Zedek Medical Center,Jerusalem,Israel
,
Eric Tse
Affiliations:
University of Hong Kong,Hong Kong,Hong Kong
,
Andrea Visentin
Affiliations:
Hematology and Clinical Immunology Unit, Department of Medicine,Università di Padova,Padova,Italy
,
Kristina Tomic
Affiliations:
Clinical Center of Serbia,Belgrade,Serbia
,
Michel van Gelder
Affiliations:
Maastricht University Medical Center,Maastricht,Netherlands
,
Theodoros Vassilakopoulos
Affiliations:
Haematology,University of Athens, Laikon General Hospital,Athens,Greece
,
Candida Vitale
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Torino,Torino,Italy;Division of Hematology,A.O.U. Città della Salute e della Scienza di Torino,Torino,Italy
,
Julia von Tresckow
Affiliations:
West German Cancer Center,University Hospital Essen, University of Duisburg-Essen,Essen,Germany
,
George Vrachiolias
Affiliations:
University Hospital of Alexandroupolis,Alexandroupolis,Greece
,
Vojin Vukovic
Affiliations:
Clinical Center of Serbia,Belgrade,Serbia
,
Zhenshu Xu
Affiliations:
Fujian Medical University Union Hospital,Fuzhou,China
,
Lucrecia Yañez
Affiliations:
University Hospital Marques de Valdecilla-IDIVAL,Santander,Spain
,
Munci Yagci
Affiliations:
Gazi University,Ankara,Turkey
,
Mohamed Yassin
Affiliations:
National Center for Cancer Care and Research, Qatar University,Doha,Qatar
,
Jana Zuchnická
Affiliations:
Department of Haemato-Oncology,University Hospital Ostrava,Ostrava,Czech Republic
,
Maria Angelopoulou
Affiliations:
Haematology,University of Athens, Laikon General Hospital,Athens,Greece
,
Darko Antic
Affiliations:
Clinical Center of Serbia,Belgrade,Serbia;University of Belgrade,Belgrade,Serbia
,
Bella Biderman
Affiliations:
National Research Center for Hematology,Moscow,Russian Federation
,
Mark Catherwood
Affiliations:
Haematology Department,Belfast City Hospital,Belfast,United Kingdom
,
Marta Coscia
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Torino,Torino,Italy;Division of Hematology,A.O.U. Città della Salute e della Scienza di Torino,Torino,Italy
,
Antonio Cuneo
Affiliations:
Hematology Unit,St. Anna University Hospital,Ferrara,Italy
,
Fatih Dermikan
Affiliations:
Dokuz Eylül University,Izmir,Turkey
,
Blanca Espinet
Affiliations:
Pathology and Hematology Services, Hospital del Mar,Barcelona,Spain
,
Gianluca Gaidano
Affiliations:
University of Eastern Piedmont,Novara,Italy
,
Luca Laurenti
Affiliations:
Hematology Unit, Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology,Fondazione Policlinico Universitario A. Gemelli IRCCS,Roma,Italy
,
Stephen Mulligan
Affiliations:
Royal North Shore Hospital and University of Sydney,Sydney,Australia
,
Eugene Nikitin
Affiliations:
The outpatient department of hematology-oncology and chemotherapy,S. P. Botkin's City Hospital,Moscow,Russian Federation
,
Panagiotis Panagiotidis
Affiliations:
1st Internal Medicine Department, Propaedeutic, Hematology Clinical Trial Unit, National and Kapodistrian University of Athens,Athens,Greece
,
Gerasimos Pangalis
Affiliations:
Iatriko Medical Center,Athens,Greece
,
Viola Maria Popov
Affiliations:
Hematology Department,Colentina Clinical Hospital,Bucharest,Romania
,
Šárka Pospíšilová
Affiliations:
Department of Internal Medicine - Hematology and Oncology,University Hospital Brno,Brno,Czech Republic;CEITEC,Masaryk University,Brno,Czech Republic
,
Lukáš Smolej
Affiliations:
4th Department of Internal Medicine - Hematology,University Hospital Hradec Králové and Charles University Faculty of Medicine,Hradec Králové,Czech Republic
,
Paolo Sportoletti
Affiliations:
Centro di Ricerche Emato-Oncologiche,Perugia,Italy
,
Niki Stavrogianni
Affiliations:
Hematology Department and HCT Unit, G. Papanicolaou Hospital,Thessaloniki,Greece
,
Constantine Tam
Affiliations:
Peter Maccallum Cancer Center,Melbourne,Australia
,
Livio Trentin
Affiliations:
Hematology and Clinical Immunology Unit, Department of Medicine,Università di Padova,Padova,Italy
,
Marek Trněný
Affiliations:
1st Department of Medicine – Department of Hematology, First Faculty of Medicine,Charles University and General Hospital in Prague,Prague,Czech Republic
,
Anastasia Chatzidimitriou
Affiliations:
INAB, CERTH,Thessaloniki,Greece
,
Paolo Ghia
Affiliations:
Università Vita Salute and IRCCS Ospedale San Raffaele,Milan,Italy;European Research Initiative on CLL,Barcelona,Spain
,
Francesc Bosch
Affiliations:
Vall d'Hebron University Hospital,Barcelona,Spain
,
Michael Doubek
Affiliations:
Department of Internal Medicine - Hematology and Oncology,University Hospital Brno,Brno,Czech Republic;CEITEC,Masaryk University,Brno,Czech Republic
Kostas Stamatopoulos
Affiliations:
European Research Initiative on CLL,Barcelona,Spain;INAB, CERTH,Thessaloniki,Greece
EHA Library. Chatzikonstantinou T. 06/09/21; 325391; EP631
Thomas Chatzikonstantinou
Thomas Chatzikonstantinou
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

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

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

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

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies