BLINATUMOMAB VS SOC CHEMOTHERAPY IN FIRST SALVAGE COMPARED WITH SECOND OR GREATER SALVAGE IN A PHASE 3 STUDY
Author(s): ,
Hervé Dombret
Affiliations:
Hôpital Saint-Louis,Paris,France
,
Max S. Topp
Affiliations:
Universitätsklinikums Würzburg,Würzburg,Germany
,
Andre Schuh
Affiliations:
Princess Margaret Cancer Center,University Health Network,Toronto,Canada
,
Andrew Wei
Affiliations:
Alfred Hospital,Monash University,Victoria,Australia
,
Giovanni Martinelli
Affiliations:
Institute of Hematology and Medical Oncology “L. e A. Seragnoili”,S. Orsola University Hospital,Bologna,Italy
,
Simon Durrant
Affiliations:
Clinical Haematology and BMT,Royal Brisbane Hospital,Herston,Australia
,
Christopher Larry Bacon
Affiliations:
St. James's Hospital,Dublin,Ireland
,
Kun Nie
Affiliations:
Global Biostatistical Sciences,Amgen,Thousand Oaks,United States
,
Zachary Zimmerman
Affiliations:
Global Development,Amgen,Thousand Oaks,United States
Hagop Kantarjian
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States
EHA Learning Center. Dombret H. Jun 24, 2017; 181765
Prof. Dr. Hervé Dombret
Prof. Dr. Hervé Dombret

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Abstract
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Abstract: S478

Type: Oral Presentation

Presentation during EHA22: On Saturday, June 24, 2017 from 16:30 - 16:45

Location: Hall E

Background
Adults with B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) often relapse following standard induction/consolidation chemotherapy (CTX). Prognosis following second and successive CTX salvage regimens (S2+) is poor compared with first salvage (S1) or frontline therapy, with less favorable outcomes among patients with shorter CR duration. Blinatumomab links cytotoxic CD3-positive T cells and CD19-positive B cells to induce tumor cell lysis. In a randomized phase 3 trial of blinatumomab vs investigator’s choice of 4 standard of care CTX (SOC) regimens, median OS was 7.7 months in the blinatumomab group vs 4.0 months with SOC (Kantarjian H, et al., NEJM 2017). Here, we evaluate outcomes by salvage status for patients in this study (NCT02013167).

Aims
To evaluate responses to blinatumomab vs SOC in patients with relapsed/refractory ALL by prior salvage therapy status.

Methods
Patients with relapsed/refractory (R/R) BCP-ALL in this international multicenter trial were randomized 2:1 to blinatumomab (n=271) or SOC (n=134). For this analysis, salvage status was adjudicated separately from prior randomization strata. Blinatumomab was given by continuous IV infusion (9 µg/d in week 1 of cycle 1, then 28 µg/d) in cycles of 4 weeks on, 2 weeks off. The primary endpoint was overall survival (OS), determined from time of randomization until death due to any cause. Adverse events (AE) of interest were coded according to MedDRA version 16.0.

Results
At baseline, patient characteristics were balanced between groups within salvage designations. The rate of complete remission, with or without full hematologic recovery (CR/CRh/CRi) in both the S1 and S2+ groups was higher in the blinatumomab arm compared with the SOC arm (Table). 

Table
 
No prior salvage (S1)
Any prior salvage (S2+)
 
Blinatumomab (n=104)
   SOC (n=63)
Blinatumomab (n=167)
   SOC (n=71)
Age ≥35 years, n (%)
65 (62.5)
37 (58.7)
82 (49.1)
37 (52.1)
Prior HSCT, n (%)
29 (27.9)
20 (31.7)
65 (38.9)
26 (36.6)
First relapse with remission duration <12 mo, n (%)
58 (55.8)
30 (47.6)
51 (30.5)
19 (26.8)
Maximum blasts ≥50% by central/local lab, n (%)
78 (75.0)
45 (71.4)
123 (73.7)
59 (83.1)
K-M Median OS, mo (95% CI)
11.1 (8.2, NR)*
5.5 (3.7, 9.0)
5.1 (3.2, 7.1)
3.0 (2.1, 4.0)
 
HR 0.59 (95% CI 0.38, 0.91) P=0.016
HR 0.72 (95% CI 0.51, 1.01) P=0.055
Best response (CR/CR/CRi), n (%) [95% CI]
53 (51.0) [41.0, 60.9]
23 (36.5) [24.7, 49.6]
66 (39.5) [32.1, 47.4]
10 (14.1) [7.0, 24.4]
 
P=0.07
P<0.001
*NR=not reached
Patients randomized to blinatumomab had a median (95% CI) of 11.1 (8.2, NR) months vs. 5.1 (3.2, 7.1) months overall survival for S1 vs. S2+ subgroup, compared with 5.5 (3.7, 9.0) months vs. 3.0 (2.1, 4.0) months in the SOC arm (Figure). For both S1 and S2+ subgroups, blinatumomab patients had longer median survival time.
Grade 3 or worse AEs were experienced by 61% and 83% of S1 patients in the blinatumomab and SOC group, respectively. These percentages were 68% and 75%, respectively, in S2+ patients. Grade 4 or worse AEs occurred in 34% and 51% S1 patients, and in 36% and 54% S2+ patients. Neurologic events of grade ≥3 occurred in 9% and 9% of S1 patients, and in 10% and 9% S2+ patients, respectively. Grade ≥3 cytokine release syndrome (CRS) was observed in 4% S1 and 5% S2+ patients receiving blinatumomab, and in no SOC patients.

Conclusion
Patients in this trial receiving blinatumomab for R/R ALL achieved improved OS and remission rates compared with SOC regardless of prior salvage therapy. Improved OS compared with SOC in S1 patients supports earlier use of blinatumomab.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): Immunotherapy, Salvage therapy, Relapsed acute lymphoblastic leukemia

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