An Observational Study of Patients with Philadelphia Chromosome-Negative Relapsed or Refractory Acute Lymphoblastic Leukemia in the US

Introduction

Treatment options are limited for adults with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) and commonly include multi-agent chemotherapy regimens. Following the approval of blinatumomab (BLINCYTO®) in the US in December 2014 for R/R Philadelphia chromosome-negative (Ph-) B-cell precursor ALL, this observational study was initiated to assess the use of blinatumomab and chemotherapy in a real-world setting with a focus on 1^st salvage therapy.

Methods

Medical records of patients initiating a treatment for R/R Ph- ALL between June 2014 and December 2016 were comprehensively reviewed to determine treatment patterns, drug and healthcare resource utilization, and clinical outcomes. Particularly, records were reviewed to assess efficacy and safety of salvage treatment. Data were collected from the time of ALL diagnosis through the first occurrence of withdrawal, loss to follow-up, enrollment in a clinical trial, death, or study conclusion. The primary analysis set included patients who received a 1^st salvage treatment within the study period. Analyses were descriptive, with continuous variables summarized by medians and categorical variables summarized with proportions and corresponding 95% confidence intervals (CIs). Incidence of adverse events was also reported. Enrollment is ongoing with interim results presented here.

Results

At the time of data cutoff for this interim analysis on May 5, 2017, 35 patients from 7 academic and community hospitals in the US were included in the primary analysis set. Of these patients, 14 received blinatumomab as 1^st salvage treatment (B1ST) and 21 received chemotherapy (C1ST). Patients who received B1ST were older (median age 60.0 years vs 30.0 years for C1ST) and more likely to be male (78.6% vs 57.1%). Patients treated with B1ST also had higher rates of cytogenetic abnormalities than those treated with C1ST (78.6% vs 38.1%) but had comparable percentages of bone marrow blasts at time of salvage therapy (median 73.5% vs 63.1%). Based on this interim snapshot, community oncologists were more likely to administered B1ST than C1ST (n=7 vs n=3) whereas the reverse trend was seen for academic oncologists (n=7 vs n=18, respectively). Baseline demographics and disease characteristics are summarized in Table 1.

Approximately 57% of the patients in the primary analysis set received subsequent lines of salvage therapy during the review period (Table 2). Overall, 21/35 (60%) of the patients in the primary analysis set received blinatumomab at some point during the review period (Table 2).

Of the treatment-emergent adverse events of grade ≥3 observed in this small group of patients, the most commonly reported in those treated with B1ST were neutropenia/febrile neutropenia (64.3%), infections (42.9%), and elevated liver enzymes (28.6%) (Table 3). One grade 3 cytokine release syndrome and one grade 3 neurological event were reported. Four patients treated with B1ST were hospitalized as a result of adverse events (n=1 each for cholestasis, colitis, eye pain, and thrombocytopenia). Of these, cholestasis, eye pain, and thrombocytopenia were considered related to blinatumomab. One patient treated with C1ST was hospitalized due to a grade 3 serious adverse event of stomatitis. Twelve deaths occurred during the review period (B1ST, n=7; C1ST, n=5); 1 death attributed to infection occurred in the B1ST group.

No emergency room visits were recorded for either group and 2 intensive care unit visits were recorded for patients in the C1ST group. All of the patients who received B1ST experienced at least 2 hospitalizations with a median length of stay of 11.3 days. Of the patients in the C1ST group, 13 were hospitalized at least once with a median length of stay of 14.0 days. The median total number of days was comparable between those hospitalized in the B1ST and C1ST groups (81.5 days and 70.0 days, respectively).

Conclusion

In this interim analysis of a real-world population of patients with R/R ALL, study data collection is ongoing. The heterogeneous baseline characteristics of the two groups suggest that higher risk patients are receiving blinatumomab as 1^st line salvage therapy in a real-world setting. No new safety signals were identified; analysis of effectiveness is ongoing.

This study was funded by Amgen.

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