Complete, yet partial: the benefits of complete response with partial haematological recovery as an endpoint in acute myeloid leukaemia clinical trials
2020; Elsevier BV; Volume: 7; Issue: 12 Linguagem: Inglês
10.1016/s2352-3026(20)30352-5
ISSN2451-9960
AutoresRory M. Shallis, Daniel A. Pollyea, Amer M. Zeidan,
Tópico(s)Hematopoietic Stem Cell Transplantation
ResumoThe ideal stepping stone on the path to cure for patients with acute myeloid leukaemia has been the achievement of a complete response (CR), the initial response most consistently associated with long-term survival. 1 Walter RB Kantarjian HM Huang X et al. Effect of complete remission and responses less than complete remission on survival in acute myeloid leukemia: a combined Eastern Cooperative Oncology Group, Southwest Oncology Group, and M. D. Anderson Cancer Center Study. J Clin Oncol. 2010; 28: 1766-1771 Crossref PubMed Scopus (152) Google Scholar Some patients who achieve less than CR, however, seem to derive benefit from particular types of therapy. Newly-diagnosed patients with acute myeloid leukaemia who receive intensive induction chemotherapy and achieve CR with incomplete haematological recovery (CRi; defined by the same criteria as CR, but with residual cytopenia such as absolute neutrophil count [ANC] <1000 cells per μL or platelet count <100 000 cells per μL) or CR with incomplete platelet recovery (CRp; similar to CRi, but specifically referring to the absence of platelet recovery) after initial therapy have worse relapse-free survival and overall survival than do patients who achieve CR, but fare better than those without response. 1 Walter RB Kantarjian HM Huang X et al. Effect of complete remission and responses less than complete remission on survival in acute myeloid leukemia: a combined Eastern Cooperative Oncology Group, Southwest Oncology Group, and M. D. Anderson Cancer Center Study. J Clin Oncol. 2010; 28: 1766-1771 Crossref PubMed Scopus (152) Google Scholar In addition to improving overall survival, the goals for patients with acute myeloid leukaemia who are unable to proceed to intensive therapy typically include reducing transfusion burden and infectious complications that threaten patient quality of life. For these reasons, the study and use of CR with partial haematological recovery (CRh)—defined as less than 5% marrow blasts, ANC greater than 500 cells per μL, and platelet count greater than 50 000 cells per μL—is both an emerging and fundamentally beneficial concept in the management of acute myeloid leukaemia. CRh was first evaluated within a composite clinical endpoint in the original phase 2 study of blinatumomab in patients with relapsed or refractory acute lymphocytic leukaemia. 2 Topp MS Gokbuget N Stein AS 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: 57-66 Summary Full Text Full Text PDF PubMed Scopus (824) Google Scholar The investigation of CRh as an endpoint has extended into the realm of acute myeloid leukaemia-directed therapies. However, CRh has been initially assessed as a part of a composite endpoint of CR or CRh in clinical trials for patients with acute myeloid leukaemia and IDH1 mutations treated with ivosidenib, IDH2 mutations treated with enasidenib, and FLT3 mutations treated with gilteritinib. 3 DiNardo CD Stein EM de Botton S et al. Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N Engl J Med. 2018; 378: 2386-2398 Crossref PubMed Scopus (707) Google Scholar , 4 Stein EM DiNardo CD Pollyea DA et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017; 130: 722-731 Crossref PubMed Scopus (815) Google Scholar , 5 Perl AE Martinelli G Cortes JE et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med. 2019; 381: 1728-1740 Crossref PubMed Scopus (421) Google Scholar , 6 Roboz GJ DiNardo CD Stein EM et al. Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood. 2020; 135: 463-471 Crossref PubMed Scopus (152) Google Scholar
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