PS961 PATIENTS WITH RELAPSED MIXED PHENOTYPE ACUTE LEUKEMIA HAVE SHORT REMISSION DURATION WITH RE‐INDUCTION: A SINGLE CENTER EXPERIENCE
Authors: Andrews C. , Murphy T. , Arruda A. , Chan S. , Gupta V. , Maze D. , McNamara C. , Schuh A. , Schimmer A. , Sibai H. , Tiernans A. , Yee K. , Minden M. 
Published: June 2019

Background:

Mixed phenotype acute leukemia (MPAL) is a heterogeneous disease consisting of acute leukemias expressing markers of both myeloid and lymphoid lineages. It is associated with a poor prognosis with a median overall survival of 11 months. There is no consensus regarding treatment at diagnosis or at relapse.

Aims:

To study the outcomes and characteristics of relapsed MPAL and identify prognostic features

Methods:

Patients aged 18 years or older meeting the criteria for MPAL according to the WHO 2016 classification in Princess Margaret Cancer Center between January 1, 2000 and December 31, 2018 were studied. Patients receiving curative intent therapy were assessed for response. The Wilcoxon‐Mann‐Whitney test for continuous variables and the Chi‐squared test for categorical variables were used.

Results:

Among the 59 MPAL patients included in this study, 42 (71%) received induction chemotherapy. Of those, 32 (76%) received ALL type treatment and 10 (24%) received AML type treatment. Tyrosine kinase Inhibitors were given to all patients who had Ph+ disease. Complete remission (CR) to ALL treatment was achieved in 26 (81%) out of 32 and 6 (50%) of the 12 patients treated with AML therapy. Eighteen (56%) of the patients relapsed with a median CR1 duration was 13.1 months. We further evaluated this group of 18 relapsed patients to identify risk factors for relapse.

One patient had isolated CNS relapse. The immunophenotype was identical to the diagnostic type for seven patients (38%). Lineage switch occurred in 9 (56%) patients. The lineage switch correlated with the treatment type with 4 (44%) patients who received ALL‐type therapy switching to AML (Table 1).

Diagnostic karyotype was reviewed for 18 patients with relapse. 16 (94%) were abnormal and classified as: complex (43%), monosomy 7 (43%), t(9;22)(q32;q11) (5%) and KMT2A rearranged (5%). There were four patients in whom karyotype was available both at the time of diagnosis and at relapse. Two (50%) had the same cytogenetic abnormality at both time points and one showed clonal evolution with an acquisition of monosomy 7.CR2 was achieved in 4 (44%) of the 9 patients that were re‐induced and the median duration was only 4.2 months. Of the 3 (75%) patients that relapsed after re‐induction, 1 patient switched lineage to blastic plasmocytoid dentritic leukemia. One patient remains in a CR2 after receiving blinatumumb with a follow up of 5 years.

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Clinical outcome data was compared between the relapsed MPAL group and the non‐relapsed MPAL group (n = 14). Males were more likely to relapse (p = 0.0209). Patients treated with ALL‐ targeted treatment were less likely to relapse than those treated with AML‐targeted treatment (p = 0.03). There was an increased number of patients in the relapsed group who were KMT2a rearranged and this approached significance (p = 0.0517). However, there was no statistical difference in relapse when accounting for age, white cell count, MPAL classification and other cytogenetic abnormalities.

Median survival after relapse was 7.6 months (range 1–72 months). Overall survival (OS) at 3 years was 5% for the relapsed patients compared to 55% of the non‐relapsed patients (Figure 1). There was no difference in OS in patients who switched lineage.

Summary/Conclusion:

This is the first report on relapsed MPAL and our findings highlights the dismal overall survival but does suggest ALL‐treatment seems more effective with a higher response rate. Further studies into the genomic aspects of the disease are needed and prospective multicenter trials are required to further appreciate this not well understood disease.