Impact of complete molecular response on survival in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia

Abstract

• In patients with Ph 1 ALL, achievement of CMR at 3 months is independently associated with improved survival.• CMR at 3 months may identify patients with Ph 1 ALL who have excellent long-term outcomes without SCT in first CR.The impact of achieving complete molecular response (CMR) in Philadelphia chromosomepositive (Ph 1 ) acute lymphoblastic leukemia (ALL) remains undefined. We evaluated the impact of CMR on outcomes among 85 patients with Ph 1 ALL who received first-line hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine plus a tyrosine kinase inhibitor, had minimal residual disease (MRD) assessments for BCR-ABL1 by quantitative polymerase chain reaction at complete remission (CR) and at 3-month time points, and did not undergo allogeneic stem cell transplantation (SCT). MRD status at 3 months had better discrimination for overall survival (OS; P 5 .005) and relapse-free survival (RFS; P 5 .002) than did MRD status at CR (P 5 .11 and P 5 .04, respectively). At 3 months, achievement of CMR vs response less than CMR was associated with longer median OS (127 vs 38 months, respectively; P 5 .009) and RFS (126 vs 18 months, respectively; P 5 .007). By multivariate analysis, only CMR at 3 months was prognostic for OS (hazard ratio, 0.42; 95% confidence interval, 0.21-0.82; P 5 .01). Patients with Ph 1 ALL who achieve CMR at 3 months have superior survival compared with those with lesser molecular responses and have excellent long-term outcomes even without SCT. (Blood. 2016;128(4):504-507)

Hyper‐CVAD plus ponatinib versus hyper‐CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia: A propensity score analysis

“…In individual studies of chemotherapy plus a TKI, deeper molecular responses have been associated with improved survival . Similar findings also have been reported in pooled analyses of patients treated with chemotherapy plus one of several TKIs . In one report of patients with Ph+ ALL who did not undergo stem cell transplantation in first remission, the achievement of CMR at 3 months was found to be independently associated with improved OS and was associated with an impressive 4‐year OS rate of 66% .…”

“…In a phase 2 trial, chemotherapy with HCVAD plus ponatinib was found to be associated with a CMR rate of 78%, which is higher than that reported with other TKIs in combination with chemotherapy . Furthermore, previous studies have suggested that deeper molecular responses in patients with Ph+ ALL are independently predictive of improved survival …”

The presence of Philadelphia chromosome does not confer poor prognosis in adult pre‐B acute lymphoblastic leukaemia in the tyrosine kinase inhibitor era – a surveillance, epidemiology, and end results database analysis

“…Studies suggest that the incorporation of TKI (imatinib) into the treatment regimen for Ph+ALL patients has led to improvements in outcomes over chemotherapy alone and, by increasing remission rates, may have lead to an increase in the percentage of patients preceding to AlloSCT (Thomas et al , ; Yanada et al , ; Fielding et al , ). A recent study showed excellent outcome for Ph+ALL patients who achieved complete molecular remission at 3 months with a combination of TKI and chemotherapy but without AlloSCT (Short et al , ). AlloSCT could potentially be restricted to patients who do not achieve a complete molecular remission or at the time of relapse.…”

TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper‐CVAD‐based regimens

“…15 For Ph-negative ALL, MRD was assessed using 6-color multiparametric flow cytometry (MFC) analysis. 16 …”