Outcome of Patients with Relapsed/Refractory (R/R) Acute Lymphoid Leukemia (ALL) after Failure of Inotuzumab Ozogamicin

Background: Patients with relapsed/refractory (R/R) ALL have limited therapeutical options. Monoclonal antibodies have shown to be effective. Inotuzumab ozogamicin (CMC-544) is a humanized anti-CD22 antibody conjugated to calicheamicin that has shown activity as a single agent in R/R ALL with 58% ORR in a phase II trial. More recently, a randomized phase III trial showed improvement of response rates of up to 80% compared to 30% for standard of care. Despite the high overall response rate to inotuzumab, responses are short-lived and most patients relapse.

Aim: The purpose of this study is to assess the outcome of patients with R/R ALL post inotuzumab ozogamicin failure.

Methods: We reviewed 151 patients with R/R ALL treated with inotuzumab ozogamicin as single agent (n=103) or part of a salvage regimen therapy (n=48) between 2009 and 2015. From this cohort of 151, we identified 67 (44%) patients with a median age of 47 years (4-84) who had either not responded to inotuzumab (n=42) or failed after a prior response of 2 months, range (<1 - 29) (n=25) and in whom a follow-up was available. These patients were evaluated for outcome analysis.

Results: Patient characteristics are listed in Table 1. The best prior response to inotuzumab included CR in 7 (10%) patients, CRp in 14 (21%), and CRi in 4 (6%). After a median follow-up of 19 months, (range, 1- 54) from inotuzumab failure, 6 patients (9%) remain alive. The median survival was 4 months, and the estimated 12-month survival rate was 13%. The median survival were 9 months, 3.5 months, and 3.4 months, respectively, for patients who received and failed inotuzumab as first salvage therapy, second salvage therapy, and third or more salvage therapy (P= 0.006). The estimated 12-month survival rates were 29%, 4%, and 10%, respectively. Patients with inotuzumab refractory disease had worse outcome post intozumab failure compared to those who responded and lost their response subsequently; the median overall survival post inotuzumab failure was 3 and 6 months (p=0.01), respectively . Among patients who relapsed, two received subsequent salvage therapy with blinatumomab. One of them responded and achieved a CR for 4 months. Four patients received an allogeneic stem cell transplantation; one of them remain alive at 55+ months.

Conclusion: Outcome after inotuzumab failure is poor with a median survival of 4.4 months; these patients should be referred to clinical trials. Further use of inotuzumab ozogamicin earlier in the course of treatment may further improve the outcome.