Outcomes of Patients with Relapsed/Refractory (R/R) B-Cell Acute Lymphocytic Leukemia (ALL) Post Blinatumomab Failure

 Introduction:  Blinatumomab is a first-in-class Bispecific T-cell engaging (BiTE) antibody targeting CD19-positive malignant cells and CD3-positive T cells.  It has shown activity in both R/R B-cell ALL and with persistent minimal residual disease (MRD).  However, despite a 50% response rate with blinatumomab, the duration of response is very short with many pts experiencing relapse.  The goal of this study is to assess the outcome of patients with R/R B-cell ALL post blinatumomab failure.

Methods: We reviewed 40 patients with R/R ALL treated with blinatumomab at our institution between 1/2012 and 1/2015.  Of the 40 patients treated, 30 were either refractory (n=18) or lost their response (n=12) after initially achieving a complete response or complete response with incomplete count recovery (CRi).  We analyzed the clinical characteristics and survival of these 30 patients who failed blinatumomab.

Results:  Clinical characteristics of the 30 patients with blinatumomab failure are summarized in Table 1. Best response to blinatumomab was CR in 9 pts and CRi in 3 with a median duration of response of 3 months (range, 1-8 months). After a median follow-up of 6.8 months (range 4.8- 31 months) from blinatumomab failure, 8 patients (27%) remain alive. The median overall survival was 6.4 months and the estimated 12-month survival rate was 36%. The median survival was 3 and 11 months for patients refractory to blinatumomab and those who relapsed after a previous response, respectively (p=0.179). Furthermore, there was a trend for better outcome post blinatumomab failure if the drug was administered as first, second, or third and beyond salvage therapy with a median survival of 19, 11, and 5 months, respectively (p= 0.248).   Following blinatumomab failure, 11 patients received inotuzumab ozogamicin salvage therapy as a single agent in 5 or in combination with mini-hyper-CVD in 6 [Jabbour E et al; EHA 2015]. Eight patients responded for an overall response rate of 73% for a median duration of 6 months (range, 1.2 -30 months).   Overall, 9 patients underwent allogeneic stem cell transplant (allo-SCT), 5 of them post salvage therapy with inotuzumab. Seven of them remain alive in CR at the last follow-up. The 1-year survival rates were 83% and 11% for patients who received an allo-SCT and those who did not, respectively (p<0.001).

Conclusions: Overall, the outcome of patients with R/R ALL post blinatumomab failure is poor with a median survival of 6.4 months. Inotuzumab ozogamicin is a good salvage therapy option allowing patients with refractory disease to proceed with allo-SCT that remains the only curative approach for these patients.

 

Table1. Clinical Characteristics of Patients with Blinatumomab Failure N=30
Parameter	N (%)/Median [Range]
Age (years)	29 [19-76]
Sex  (Male)	23 (77)
Performance Status	1 [0-2]
Cytogenetics
Diploid	9 (30)
t(4;11)	1 (3)
Miscellaneous	15 (50)
t(9;22)	1 (3)
Insufficient Metaphase	4 (14)
WBC at start (x 109/L)	2.75 [0.4-24]
% PB blasts at start	8 [0-98]
% BM Blasts at start	80 [10-98]
WBC at failure (x 109/L)	3.4 [0-224]
% BM Blasts at failure	69 [2-98]
# Prior therapies, median	3 [1-6]
# Blinatumomab courses	2 [1-5]
Best response to blinatumomab
CR	9 (30)
CRi	3 (10)
Median duration of response (months)	3 [1-8]
Follow up, median (months)	6.8 [4.8-31]