Beyond Guidelines: Real World Treatment & Outcomes of Chronic Lymphocytic Leukemia at a Tertiary Indian Cancer Centre
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Abstract
Background: Chronic Lymphocytic Leukemia (CLL) is the most common type of leukemia diagnosed in the United States and accounts for about one-quarter of the newly diagnosed cases while it is one of the least common leukemias in India (< 5% of all leukemias) with incidence rates ten times lesser than in the US. There is a dearth of data on regional characteristics and treatment outcomes of the disease; especially from India
Methods: This is a retrospective single centre study conducted among 63 newly diagnosed CLL patients at a tertiary cancer care centre in India from January 2020 to December 2023. The various demographic, clinicopathological characteristics and response to various treatment regimens were recorded. Relapse-free survival, Time to next treatment and Overall survival were the end points studied. The median follow up period was 17 months.
Results: In contrast to the Western data, majority of our patients presented in the younger cohort, with patients aged<= 55 years comprising 36.5% of the total patient population, with a median age of 60 years (about a decade lesser than our Western counterparts). Majority of our patients (88.9%) were symptomatic for the disease at presentation and required initiation of treatment.
Deletion 13q(del 13q) was the most common genetic abnormality seen in our population and deletion 11q(del 11q ) the least. Deletion 17p(del 17p) was positive in 30.2% cases upfront and the hazard ratio for relapse was found to be 11.26(95% CI: 2.9,42.7; p=0.0001) in those patients.
The various regimens used in the study were primarily Bruton Tyrosine Kinase inhibitors (BTKis), Bendamustine-Rituximab regimen (BR)and Chlorambucil-Wysolone combination.
All the patients treated with Ibrutinib (BTKi) achieved a complete response (CR) at the end of 6 months, with no documented relapses. BR regimen was the most common regimen found to have been used among the relapsed cases and the hazard ratio for relapse in patients treated with BR regimen was found to be 3.37(95% CI: 0.90,12.5; p=0.069) with a trend towards statistical significance.
Median relapse free survival was found to be 17.6 months & median time to next treatment was found to be 10.9 months. The Median Overall survival was not reached in this study.
This study concludes that Chronic Lymphocytic Leukemia seems to be more aggressive in Indian patients with younger age of presentation, higher disease burden, higher incidence of del 17p, shorter time to first treatment, more frequent relapses and lesser time to next treatment. BTKis seem to be the best treatment regimen for CLL patients. Chlorambucil-wysolone regimen was found to have better survival benefit as compared to the BR regimen.
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References
2. Yang, S.-M., Li, J.-Y., Gale, R. P. & Huang, X.-J. The mystery of chronic lymphocyticleukemia (cll): Why is it absent in asians and what does this tell us about etiology, pathogenesis and biology? Blood reviews 29, 205–213 (2015).
3. Gunawardana, C. et al. South asian chronic lymphocytic leukaemia patients have more rapid disease progression in comparison to white patients. British journal of haematology 142, 606–609 (2008).
4. Belinda Austen, Chaminda Gunawardana, Guy Pratt, Farooq Wandroo, Abe Jacobs, Judith Powell, Paul Moss; Chronic Lymphocytic Leukaemia Has a More Aggressive Phenotype in Asians Compared to Caucasians. Blood 2006; 108 (11): 4965. doi: https://doi.org/10.1182/blood.V108.11.4965.4965
5. Hallek, M. et al. iwcll guidelines for diagnosis, indications for treatment, response assessment, and supportive management of cll. Blood, The Journal of the American Society of Hematology 131, 2745–2760 (2018).
6. Puiggros, A., Blanco, G. & Espinet, B. Genetic abnormalities in chronic lymphocytic leukemia: where we are and where we go. BioMed research international 2014, 435983 (2014).
7. Stefaniuk, P., Onyszczuk, J., Szymczyk, A. & Podhorecka, M. Therapeutic options for patients with tp53 deficient chronic lymphocytic leukemia: Narrative review. Cancer management and research 1459–1476 (2021).
8. Shanafelt, T. D. et al. Ibrutinib–rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. New England Journal of Medicine 381, 432–443 (2019).
9. Stephens, D. M. Nccn guidelines update: Chronic lymphocytic leukemia/small lymphocytic lymphoma. Journal of the National Comprehensive Cancer Network 21, 563–566 (2023).
10. Hallek, M. Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment. American journal of hematology 94, 1266–1287 (2019).
11. Parikh, S. A. et al. Chronic lymphocytic leukemia in young (<=55 years) patients:a comprehensive analysis of prognostic factors and outcomes. haematologica 99,140 (2014).
12. Francesca R. Mauro, Robert Foa, Diana Giannarelli, Iole Cordone, Sabrina Crescenzi, Edoardo Pescarmona, Roberta Sala, Raffaella Cerretti, Franco Mandelli; Clinical Characteristics and Outcome of Young Chronic Lymphocytic Leukemia Patients: A Single Institution Study of 204 Cases. Blood 1999; 94 (2): 448–454. doi: https://doi.org/10.1182/blood.V94.2.448
13. Ferrajoli, A. Treatment of younger patients with chronic lymphocytic leukemia.Hematology 2010, the American Society of Hematology Education Program Book2010, 82–89 (2010).
14. Tejaswi, V and Lad, Deepesh P and Jindal, Nishant and Prakash, Gaurav and Malhotra, Pankaj and Khadwal, Alka and Jain, Arihant and Sreedharanunni, Sreejesh and Sachdeva, Manupdesh Singh and Naseem, Shano and others. Chronic lymphocytic leukemia: real-world data from india. JCO Global Oncology 6, 866–872 (2020).
15. Agrawal, N. et al. Chronic lymphocytic leukemia in india-a clinico-hematological profile. Hematology 12, 229–233 (2007).
16. Rani, L. et al. Comparative assessment of prognostic models in chronic lymphocytic leukemia: evaluation in indian cohort. Annals of Hematology 98, 437–443(2019).
17. Choi, Y. et al. Treatment outcome and prognostic factors of korean patients with chronic lymphocytic leukemia: a multicenter retrospective study. The Korean Journal of Internal Medicine 36, 194 (2021).
18. Wainman, L. M., Khan, W. A. & Kaur, P. Chronic lymphocytic leukemia: Current knowledge and future advances in cytogenomic testing. Exon Publications 93–106(2023).
19. Molica, S. Sex differences in incidence and outcome of chronic lymphocytic leukemia patients. Leukemia & lymphoma 47, 1477–1480 (2006).
20. Molica, S. et al. The chronic lymphocytic leukemia international prognostic index predicts time to first treatment in early cll: Independent validation in a prospective cohort of early stage patients. American journal of hematology 91, 1090–1095(2016).
21. Delgado, J. et al. Chronic lymphocytic leukaemia with 17p deletion: a retrospective analysis of prognostic factors and therapy results. British journal of haematology 157, 67–74 (2012).
22. Konstantinov, S. & Berger, M. Alkylating agents. Encyclopedia of Molecular Pharmacology; Offermanns, S., Rosenthal, W., Eds 53–57 (2008).
23. Lipsky, A. & Lamanna, N. Managing toxicities of bruton tyrosine kinase inhibitors. Hematology 2014, the American Society of Hematology Education Program Book 2020, 336–345 (2020).
24. Zenz, T. et al. Risk categories and refractory cll in the era of chemoimmunotherapy.Blood, The Journal of the American Society of Hematology 119, 4101–4107(2012).