Akut Lenfoblastik Lösemili çocuk hastalarda Hedefe Yönelik Yaklaşımlar

Yıl 2024, Cilt: 46 Sayı: 6, 1002 - 1014, 07.11.2024

Zeynep Canan Özdemir , Yüksel Öztürk

https://doi.org/10.20515/otd.1518969

Öz

Akut lenfoblastik lösemi (ALL), olgunlaşmamış lenfosit formlarının kemik iliğinde kontrolsüz bir şekilde çoğalması nedeni oluşan malign bir hastalıktır. Ülkemizde çocukluk çağının en sık görülen kanseridir. Hastaların %75ini B hücreli ALL (B-ALL), %25ini T hücreli ALL (T-ALL) oluşturur. Çağdaş tedavi yaklaşımları, ALL için 5 yıllık olaysız sağkalım ve genel sağkalım oranlarını sırasıyla %80 ve %90'ın üzerine çıkarmış ve kümülatif nüks riskini %10'un altına düşürmüştür. Nüks olan %10’luk hasta grubunda tedavi sonuçlarında ve yaşam kalitesinde daha fazla iyileşme sağlanması için yeni terapötik yaklaşımların kullanılması ve geliştirilmesi gereklidir. Relaps/refrakter (R/R) prekürsör B- ALL’de moleküler hedefli tedaviler, standart kemoterapilerin neden olduğu toksisitelerin yükünü azaltmada ve kalıntı hastalık ile mücadele etmede önemli fırsatlar sunar.

Anahtar Kelimeler

B hücreli lenfoblastik lösemi, Çocuk, Hedefe Yönelik Yaklaşımlar, Akut Prekürsör B Hücreli Lenfoblastik Lösemi, Blinatumomab

Targeted Approaches in Acute Lymphocytic Leukemia

Öz

Acute lymphoblastic leukemia (ALL) is a malignant disease caused by the uncontrolled proliferation of immature lymphocyte forms in the bone marrow. It is the most common cancer of childhood in our country. 75% of the patients are B-cell ALL (B-ALL), 25% are T-cell ALL (T-ALL). Contemporary treatment approaches have increased the 5-year event-free survival and overall survival rates for ALL to over 80% and 90%, respectively, and reduced the cumulative risk of recurrence to less than 10%. It is necessary to use and develop new therapeutic approaches to further improve treatment outcomes and quality of life in the 10% of patients with relapse. In relapsed/refractory (R/R) precursor B-ALL, molecularly targeted therapies offer significant opportunities to reduce the burden of toxicities caused by standard chemotherapies and combat residual disease.

Anahtar Kelimeler

B cell Lymphoblastic leukemia, Pediatric, Molecularly Targeted Therapy, Acute Precursor B Cell Lymphoblastic Leukemia, Blinatumomab

Kaynakça

• 1. Hunger SP, Mullighan CG. Acute Lymphoblastic Leukemia in Children. N Engl J Med. 2015;373(16):1541-52.
• 2. Stein A, Franklin JL, Chia VM, Arrindell D, Kormany W, Wright J, et al. Benefit-Risk Assessment of Blinatumomab in the Treatment of Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. Drug Saf. 2019;42(5):587-601.
• 3. Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–47.
• 4. Gokbuget N, Dombret H, Ribera JM, Fielding AK, Advani A, Bassan R, et al. International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia. Haematologica. 2016;101(12):1524–33.
• 5. Topp MS, Gökbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S, et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014;32(36):4134-40.
• 6. Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57-66.
• 7. Martinelli G, Boissel N, Chevallier P, Ottmann O, Gökbuget N, Rambaldi A, et al. Long-term follow-up of blinatumomab in patients with relapsed/refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukaemia: Final analysis of ALCANTARA study. Eur J Cancer. 2021;146:107-114.
• 8. von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett T, Rizzari C, et al. Phase 1/2 study in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) receiving blinatumomab treatment. Blood. 2014;124:2292.
• 9. von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2016;34(36):4381-4389.
• 10. Gökbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, et al. Blinatumomab for minimal residual disease in adults with b-cell precursor acute lymphoblastic leukemia. Blood. 2018; 131(14):1522–31.
• 11. Handgretinger R, Zugmaier G, Henze G. Kreyenberg H, Lang P, von Stackelberg A. Complete remission after blinatumomab-induced donor T-cell activation in three pediatric patients with post-transplant relapsed acute lymphoblastic leukemia. Leukemia. 2011; 25: 181–184
• 12. Schlegel P, Lang P, Zugmaier G, Ebinger M, Kreyenberg H, Witte KE, et al. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab. Haematologica. 2014;99(7):1212-9.
• 13. Locatelli F, Whitlock JA, Peters C, Chen-Santel C, Chia V, Dennis RM, et al. Blinatumomab versus historical standard therapy in pediatric patients with relapsed/refractory Ph-negative B-cell precursor acute lymphoblastic leukemia. Leukemia. 2020;34(9):2473-2478.
• 14. Locatelli F, Zugmaier G, Mergen N, Bader P, Jeha S, Schlegel PG, et al. Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study [published correction appears in Blood Cancer J. 2021 Feb 1;11(2):28. doi: 10.1038/s41408-021-00413-7] [published correction appears in Blood Cancer J. 2021 Oct 27;11(10):173. doi: 10.1038/s41408-021-00567-4]. Blood Cancer J. 2020;10(7):77. Published 2020 Jul 24.
• 15. Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, et al. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021;325(9):833-842.
• 16. Locatelli F, Zugmaier G, Rizzari C, Morris JD, Gruhn B, Klingebiel T, et al. Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021;325(9):843-854.
• 17. Gaballa MR, Banerjee P, Milton DR, Jiang X, Ganesh C, Khazal S, et al. Blinatumomab maintenance after allogeneic hematopoietic cell transplantation for b-lineage acute lymphoblastic leukemia. Blood. 2022; 139(12):1908–19.
• 18. Hodder A, Mishra AK, Enshaei A, Baird S, Elbeshlawi I, Bonney D, et al. Blinatumomab for First-Line Treatment of Children and Young Persons With B-ALL. J Clin Oncol. 2024;42(8):907-914.
• 19. Lu J, Qiu H, Wang Y, Zhou X, Dai H, Lu X, et al. Reduced-dose chemotherapy and blinatumomab as induction treatment for newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia: a phase 2 trial. J Hematol Oncol. 2024;17(1):79.
• 20. Bassan R, Chiaretti S, Della Starza I, Spinelli O, Santoro A, Elia L, et al. Preliminary results of the GIMEMA LAL2317 sequential chemotherapy-blinatumomab frontline trial for newly diagnosed adult Ph-negative B-lineage ALL patients. HemaSphere. 2021;5(S2):8.
• 21. Boissel N, Huguet F, Leguay T, Hunault M, Kim R, Hicheri Y, et al. Blinatumomab during Consolidation in High-Risk Philadelphia Chromosome (Ph)-Negative B-Cell Precursor (BCP) Acute Lymphoblastic Leukemia (ALL) Adult Patients: A Two-Cohort Comparison within the Graall-2014/B Study. Blood. 2022;140:507-509.
• 22. Foà R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo MC, et al. Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults. N Engl J Med. 2020;383:1613-1623.
• 23. Jabbour E, Short NJ, Jain N, Huang X, Montalban-Bravo G, Banerjee P, et al. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023;10:e24-e34.
• 24. Curran E, Muffly L, Luskin MR. Innovative Approaches to the Management of Acute Lymphoblastic Leukemia Across the Age Spectrum. Am Soc Clin Oncol Educ Book. 2022 Apr;42:1-11.
• 25. Foà R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo MC, et al; GIMEMA Investigators. Dasatinib-blinatumomab for Ph-positive acute lymphoblastic leukemia in adults. N Engl J Med.2020;383:1613-1623.
• 26. Jabbour E, Patel K, Jain N, Duose D, Luthra R, Short NJ, et al. Impact of Philadelphia chromosome-like alterations on efficacy and safety of blinatumomab in adults with relapsed/refractory acute lymphoblastic leukemia: A post hoc analysis from the phase 3 TOWER study. Am J Hematol. 2021;96(10):E379-E383.
• 27. Elitzur S, Arad-Cohen N, Barzilai-Birenboim S, Ben-Harush M, Bielorai B, Elhasid R, et al. Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B-cell precursor acute lymphoblastic leukemia: Report from the Israeli Study Group of Childhood Leukemia. Pediatr Blood Cancer. 2019;66(10):e27898. 28. Pieters R, Schrappe M, De Lorenzo P, Hann I, De Rossi G, Felice M, et al. A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet. 2007;370(9583):240-250.
• 29. Pieters R, De Lorenzo P, Ancliffe P, Aversa LA, Brethon B, Biondi A, et al. Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study. J Clin Oncol. 2019;37(25):2246-2256.
• 30. Clesham K, Rao V, Bartram J, Ancliff P, Ghorashian S, O'Connor D, et al. Blinatumomab for infant acute lymphoblastic leukemia. Blood. 2020;135(17):1501-1504.
• 31. van der Sluis IM, de Lorenzo P, Kotecha RS, Attarbaschi A, Escherich G, Nysom K, et al. Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia. N Engl J Med. 2023;388(17):1572-1581.
• 32. Conde-Royo D, Juárez-Salcedo LM, Dalia S. Management of adverse effects of new monoclonal antibody treatments in acute lymphoblastic leukemia. Drugs Context. 2020:2020-7-2. doi: 10.7573/dic.2020-7-2. PMID: 33110433.
• 33. Stein AS, Schiller G, Benjamin R, Jia C, Zhang A, Zhu M, et al. Neurologic adverse events in patients with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab: management and mitigating factors. Ann Hematol. 2019;98(1):159–167
• 34. Klinger M, Zugmaier G, Nägele V, Goebeler ME, Brandl C, Stelljes M, et al. Adhesion of T cells to endothelial cells facilitates blinatumomab-associated neurologic adverse events. Cancer Res. 2020;80(1):91–101.
• 35. Alfayez M, Kantarjian HM, Short NJ, Assi R, Khouri M, Ravandi F, et al. Safety and efficacy of blinatumomab in patients with Central Nervous System (CNS) disease: a single institution experience. Blood. 2018;132(Suppl 1):2702.
• 36. Turtle CJ, Hanafi L-A, Berger C, Gooley TA, Cherian S, Hudecek M,et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest. 2016;126(6):2123–2138.
• 37. Frey N. Cytokine release syndrome: who is at risk and how to treat. Best Pract Res Clin Haematol. 2017;30(4):336–340.
• 38. Offidani M, Corvatta L, Malerba L, Marconi M, Leoni P. Infectious complications in adult acute lymphoblastic leukemia (ALL): experience at one single center. Leuk Lymphoma. 2004;45(8):1617–1621.
• 39. Klinger M, Brandl C, Zugmaier G, et al. Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood. 2012;119(26):6226–6233.
• 40. Giebel S, Thomas X, Hallbook H, Geissler K, Boiron JM, Huguet F, et al. The prophylactic use of granulocyte-colony stimulating factor during remission induction is associated with increased leukaemia-free survival of adults with acute lymphoblastic leukaemia: a joint analysis of five randomised trials on behalf of the EWALL. Eur J Cancer. 2012;48(3):360–367.
• 41. Kantarjian HM, Stein AS, Bargou RC, Grande Garcia C, Larson RA, Stelljes M, et al. Blinatumomab treatment of older adults with relapsed/refractory B-precursor acute lymphoblastic leukemia: results from 2 phase 2 studies. Cancer. 2016;122(14):2178–2185.
• 42. Martinelli G, Boissel N, Chevallier P, Ottmann O, Gökbuget N, Topp MS, et al. Complete hematologic and molecular response in adult patients with relapsed/ refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol. 2017;35(16):1795-1802.
• 43. Mikulska M, Lanini S, Gudiol C, Drgona L, Ippolito G, Fernández-Ruiz M, et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective (agents targeting lymphoid cells surface antigens [I]: CD19, CD20 and CD52). Clin Microbiol Infect. 2018;24(Suppl 2):S71–S82.
• 44. Darvishi B, Farahmand L, Jalili N, Majidzadeh-A K. Blinatumomab provoked fatal heart failure. Int Immunopharmacol. 2016;41: 42–46.