Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience

Abstract

A total of 1569 patients with chronic myeloid leukemia (CML) referred to our institution within 1 month of diagnosis since 1965 were reviewed: 1148 chronic phase (CP), 175 accelerated phase (AP), and 246 blastic phase (BP). The median survival was 8.9 years in CP, 4.8 years in AP, and 6 months in BP. In CP, the 8-year survival was ≤ 15% before 1983, 42%-65% from 1983-2000, and 87% since 2001. Survival was worse in older patients (P = .004), but this was less significant since 2001 (P = .07). Survival by Sokal risk was significantly different before 2001 (P < .001), but not since 2001 (P = .4). In AP, survival improved over time (P < .001); the 8-year survival in patients treated since 2001 was 75%. Survival by age was not different in years < 2001 (P = .09), but was better since 2001 in patients ≤ 70 years of age (P = .004). In BP, the median survival improved over time (P < .001), although it has been only 7 months since 2001. In summary, survival in CML has significantly improved since 2001, particularly so in CP-AML and AP-CML. Imatinib therapy minimized the impact of known prognostic factors and Sokal risk in CP-CML and accentuated the impact of age in AP- and BP-CML.

The clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study

“…The course of chronic myeloid leukemia (CML) has dramatically improved since imatinib mesylate (IM), the first member of a family of tyrosine kinase inhibitors (TKI) with BCR-ABL1 blocking activity, was made available for clinical use [1]. In contrast with most anti-cancer drugs, IM and next generation TKIs are administered at fixed dose (most often 400 mg of IM daily during the chronic phase of the disease) irrespective of the patient's physical characteristics, including weight, body surface and body mass index (BMI).…”

Measurement ofBCR-ABL1transcripts on the International Scale in the United States: current status and best practices

“…MMR was established in IRIS as a critical prognostic threshold (and treatment goal) at 12-18 months of imatinib therapy for predicting a prolonged subsequent remission. [7,25] BCR-ABL1 levels on the IS are reported as percentages; thus, BCR-ABL1 IS 0.1%, 0.01%, and 0.0032% are equivalent to MMR (also known MR 3 ), MR 4 , and MR 4.5 , respectively, with the superscript indicating the log reduction in BCR-ABL1 RNA from the IRIS baseline. [2,5] Although the 30 samples from IRIS upon which the IS baseline level was defined have been exhausted, laboratories are able to calibrate their individual BCR-ABL1 RQ-PCR assays to the IS by either of two methods.…”

“…[1] Since receiving US Food and Drug Administration (FDA) approval in 2001, [2] the BCR-ABL1 tyrosine kinase inhibitor (TKI) imatinib has improved the prognosis for patients with Ph þ CML compared with previously available therapeutic approaches. [3,4] Several more potent secondgeneration TKIs (i.e. nilotinib, dasatinib, bosutinib, and ponatinib) have since been developed and approved for the treatment of Ph þ CML in chronic phase (CML-CP) as frontline and/or subsequent treatment options.…”

“…[2,5] Long-term follow-up data from the International Randomized Study of Interferon versus STI571 (IRIS) trial show that most patients with CML-CP treated with frontline imatinib achieved complete cytogenetic response (CCyR; defined as the absence of Ph þ metaphases) and major molecular response (MMR; BCR-ABL1 0.1% on the International Scale [BCR-ABL1 IS ]). [6,7] However, in the Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd; nilotinib 300 mg twice daily [BID] versus nilotinib 400 mg BID versus imatinib) and DASatinib versus Imatinib Study In treatment-Naive CML patients (DASISION; dasatinib 100 mg once daily versus imatinib) studies, fewer patients achieved MMR or deeper molecular responses of molecular response 4 (MR 4 ; BCR-ABL1 IS 0.01%) or molecular response 4.5…”

Induction of Heme Oxygenase-1 by Na+-H+ Exchanger 1 Protein Plays a Crucial Role in Imatinib-resistant Chronic Myeloid Leukemia Cells

“…Nonetheless, some patients with chronic phase CML resist IM mainly due to mutation in BCR-ABL1 that affects the binding site of IM (7)(8)(9)(10). Additionally, some patients are intolerant to IM treatment because of adverse events (11,12). Novel BCR/ABL inhibitors such as nilotinib (AMN107) and dasatinib (BMS354825) have managed to overcome IM resistance mediated by various BCR/ABL point mutations (13)(14)(15).…”