The clinical impact of time to response in de novo accelerated‐phase chronic myeloid leukemia

Abstract

We aimed to describe the impact of time to response on the outcomes of 75 patients with accelerated‐phase chronic myeloid leukemia (CML‐AP) at diagnosis. Patients had at least 1 feature of AP: blasts ≥15% (n = 2), basophils ≥20% (n = 19), platelets <100 × 109/L (n = 7), cytogenetic clonal evolution (n = 34), or more than one factor (n = 13). Thirty‐three patients received imatinib; 42 received a second‐generation tyrosine kinase inhibitor (2GTKI) (19 dasatinib and 23 nilotinib). We used chi‐square and Kaplan‐Meier analyses to determine the impact of various degrees of molecular and cytogenetic response at early time points (3 and 6 months) on rates of overall cytogenetic and molecular response, overall survival (OS), event‐free survival (EFS), transformation‐free survival (TFS), and failure‐free survival (FFS). After a median follow‐up of 96 months (range: 18‐224 months), the overall rate of complete cytogenetic response was 79%, of major molecular response, 71%, and of molecular reponse (MR)4.5, 59%. Patients who achieved a major cytogenetic response (MCyR) (n = 49) at 3 months had significantly better 3‐year OS (94% vs 75%; P = .002), TFS (98% vs 73%; P < .001), EFS (93% vs 42%; P < .001), and FFS (83% vs 25%; P < .001) rates than patients who did not have MCyR at 3 months. Most (67%) who eventually achieved sustained MR4.5 had achieved MCyR at 3 months. In de novo CML‐AP, early response at 3 and 6 months is a strong determinant of long‐term outcome.

Accelerated Phase Chronic Myeloid Leukemia and Treatment Free Remission Maintained After Five Years of Nilotinib: A Case Report

“…A recent study (25) including 75 patients with accelerated phase CML at diagnosis, twenty-three of whom were treated with nilotinib upfront, has suggested the association between early response at 3 and 6 months to be a strong determinant of longterm outcome. This is also compatible with observations from our experience with a patient with accelerated phase CML and elevated risk scores: after a 5-year treatment with nilotinib, the patient reached a successful TFR, maintaining deep molecular remission for more than five years (total observation period 10 years).…”

Classification of accelerated phase chronic myeloid leukemia in the era of the BCR::ABL1 tyrosine kinase inhibitors: A work in progress

“…The same happened in CML‐AP. The benefit was particularly notable in patients who presented with de novo CML‐AP, where the estimated 10‐year OS rate increased to 70+%, thus questioning the value of these “acceleration” criteria as warning signs for an imminent adverse outcome 9,10 . In CML‐AP evolving after a period of TKI therapy for CML‐CP, the situation was different: While OS improved, the CML‐AP characteristics still predicted for an adverse outcome 11 …”

“…The benefit was particularly notable in patients who presented with de novo CML-AP, where the estimated 10-year OS rate increased to 70+%, thus questioning the value of these "acceleration" criteria as warning signs for an imminent adverse outcome. 9,10 In CML-AP evolving after a period of TKI therapy for CML-CP, the situation was different: While OS improved, the CML-AP characteristics still predicted for an adverse outcome. 11 The World Health Organization (WHO) classification historically included CML-AP criteria that relied on the published literature and the collective experience of a clinical advisory committee.…”

Current status and novel strategy of CML

“…The definition of CML-BP is as follows: ≥ 20% blasts (either myeloid or lymphoid) in peripheral blood and/or bone marrow or the presence of extramedullary disease [12]. The estimated 3-year survival of patients with CML-AP is reported to be 70-90% with TKI therapy [13]. Prognosis of CML-BP has been improved, especially with the combination of TKI and systemic chemotherapy with a median overall survival (OS) of 1-3 years [14].…”