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1298 Outcome of Patients with Relapsed/Refractory (R/R) Acute Lymphoid Leukemia (ALL) after Failure of Inotuzumab Ozogamicin

Acute Lymphoblastic Leukemia: Clinical Studies
Program: Oral and Poster Abstracts
Session: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Poster I
Saturday, December 5, 2015, 5:30 PM-7:30 PM
Hall A, Level 2 (Orange County Convention Center)

Jad Chahoud, MD1, Hagop M. Kantarjian, MD2, Guillermo Garcia-Manero, MD2, Koji Sasaki, MD2, Tapan Kadia, MD2, Jorge E. Cortes, MD2, Maria R. Khouri3*, Farhad Ravandi, MD2, Jenny Dahl, PA4*, Alessandra Ferrajoli, MD2, Jovitta Jacob, RN2*, Naveen Pemmaraju, MD2, Naval Daver, MD2, Rebecca Garris2* and Elias Jabbour2

1University of Texas Hosuton Health Science Center, Houston, TX
2Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
3Department of Stem Cell Transplantation & Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
4Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston

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.

 

Table 1 – Patient Characteristics

 

Characteristics

n = 67

 

N

(%)

Median age, [range]

47 [4-84]

Age

 

 

< 40

29

(43)

40-60

16

(24)

>60

22

(33)

Sex

 

 

M

30

(45)

F

37

(55)

Performance Status

 

 

0-1

59

(88)

2

7

(10)

3

1

(1)

ALL sub-type

 

 

Pre-b ALL

65

(97)

biphenotypic

2

(3)

Cytogenetics

 

 

Ph+

11

(16)

t(4;11)

9

(13)

Complex

13

(19)

Diploid

8

(12)

Other

26

(39)

Hematological Parameters

 

 

Median WBC at start

4.1 [0.3-48.5]

Median WBC at Fail

2.3 [0-121.4]

Median PB, blasts at start

24.5 [0-93]

Median, PB, Blasts at fail

5.1 [0-96]

Median BM Blasts at start

75 [13-98]

Median BM Blasts at fail*

65 [0-99]

Timing of Inotuzumab after Relapse

 

 

as first salvage therapy

21

(31)

as second salvage therapy

27

(40)

as ≥ third salvage therapy

19

(28)

Number of Inotuzumab cycles

 

 

1 to 2 cycles

42

(63)

3 to 4 cycles

18

(27)

5 to 6 cycles

7

(10)

* Patients with 0 BM Blast had extramedullary disease

Disclosures: Chahoud: American Society of Hematology (ASH): Other: 2015 HONORS Award recipient . Off Label Use: Inotuzumab.. Cortes: Novartis: Consultancy , Research Funding ; Pfizer: Consultancy , Research Funding ; BMS: Consultancy , Research Funding ; Teva: Research Funding ; BerGenBio AS: Research Funding ; Ariad: Consultancy , Research Funding ; Astellas: Consultancy , Research Funding ; Ambit: Consultancy , Research Funding ; Arog: Research Funding ; Celator: Research Funding ; Jenssen: Consultancy . Pemmaraju: Stemline: Research Funding ; Incyte: Consultancy , Honoraria ; Novartis: Consultancy , Honoraria , Research Funding ; LFB: Consultancy , Honoraria .

*signifies non-member of ASH