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Relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) has poor outcomes in patients with survival of less than 6 months. The development of novel targeted therapies such as bispecific T-cell engager (BiTE) and chimeric antigen receptor (CAR) T-cell therapy have significantly improved outcomes in R/R ALL. However, there remains a discrepancy in the survival rates among patients with R/R B-cell precursor receiving first, second, third, or later salvage.
Topp M. S. and colleagues recently published a study in Cancer Medicine, assessing the efficacy and safety of blinatumomab as first versus second or later salvage in patients with R/R B-cell precursor ALL.1 The findings from this study are summarized below.
The study was a comparative analysis using patient level pooled data of 532 patients from two phase II, and one phase III study.2−4 The patients were aged ≥18 years, and had an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
Eligible patients included in the study received blinatumomab in cycles of 4-week continuous infusion followed by a 2-week treatment-free interval (first salvage, n = 165; and second or later salvage, n = 367)
Patients receiving blinatumomab as first salvage were older and had had slightly better ECOG performance status compared with those receiving second or later salvage (Table 1). More than 25% of patients in both groups had prior allogenic hematopoietic stem cell transplant (allo-HSCT).
Table 1. Baseline characteristics.*
Characteristic |
First Salvage |
Second or later salvage |
---|---|---|
Median (range) age, years |
45 (19−80) |
34 (18−77) |
Sex, n (%) Men Women |
98 (59) 67 (41) |
225 (61) 142 (39) |
ECOG performance status, n (%) 0 1 2 Unknown |
77 (47) 72 (44) 16 (10) 0 (0) |
111 (30) 191 (52) 63 (17) 2 (1) |
Prior allo-HSCT, n (%) |
41 (25) |
141 (38) |
Median (range) bone marrow blasts at screening, % |
78 (1−100) |
81 (2−100) |
Bone marrow blasts, n (%) ≤ 5% > 5%−< 10% 10%−< 50% ≥ 50% Unknown |
8 (5) 9 (6) 35 (21) 99 (60) 14 (9) |
8 (2) 13 (4) 78 (21) 250 (68) 18 (5) |
ECOG, Eastern Cooperative Oncology Group; allo-HSCT, allogeneic hematopoietic stem cell transplant. *Data from Topp et al.1 |
Table 2. OS and RFS.*
Patient group |
Median OS, months (95% CI) |
HR; p value |
---|---|---|
First salvage |
10.4 (8.3−14.3) |
1.58; p < 0.001 |
Second or later salvage |
5.7 (4.3−7.1) |
|
First salvage + prior allo-HSCT |
14.7 (8.3−25.3) |
|
First salvage + no prior allo-HSCT |
9.3 (7.7−13.5) |
|
Second or later salvage + prior allo-HSCT |
7.4 (4.2−9.0) |
|
Second or later salvage + no prior allo-HSCT |
4.9 (3.9−6.7) |
|
Patient group |
Median RFS, months (95% CI) |
HR; p value |
First salvage |
10.1 (7.4−18.0) |
1.38; p = 0.061 |
Second or later salvage |
7.3 (5.7−9.6) |
|
allo-HSCT, allogeneic hematopoietic stem cell transplant; CI, confidence interval; HR, hazard ratio; OS, overall survival; RFS, relapse-free survival. *Data from Topp et al.1 |
Table 3. Best response, MRD, and transplant.*
Best response, MRD, and transplant |
First Salvage |
Second or later salvage |
---|---|---|
Best response after two cycles |
|
|
MRD response after two cycles† |
|
|
Patients with allo-HSCT |
60 (36) [29−44] |
88 (24) [20−29] |
Patients transplanted in continuous remission post-blinatumomab |
33 (20) [14−27] |
52 (14) [11−18] |
Patients with anti-leukemic treatment other than blinatumomab |
42 (26) [19−33] |
61 (17) [13−21] |
Patients transplanted after relapse post-blinatumomab and/or refractory post-blinatumomab |
4 (2) [1−6] |
9 (3) [1−4] |
allo-HSCT, allogenic hematopoietic stem cell transplant; CI, confidence interval; CR, complete remission with full hematologic recovery; CRh, CR with partial hematologic recovery; Cri, CR with incomplete hematologic recovery; MRD, minimal residual disease. *Data from Topp et al.1 †Bone marrow blasts <10−4. |
Table 4. Adverse events.*
Event |
First Salvage (n = 165) |
Second or later salvage (n = 367) |
||
---|---|---|---|---|
Any grade, n (%) |
Grade ≥3, n (%) |
Any grade, n (%) |
Grade ≥3, n (%) |
|
Patients with any TEAE |
162 (99) |
133 (81) |
361 (99) |
310 (85) |
Patients with any treatment emergent serious AE |
99 (60) |
— |
239 (66) |
— |
Patients with a fatal TEAE |
16 (10) |
— |
76 (21) |
— |
Patients with a fatal treatment-related AE |
3 (2) |
— |
10 (3) |
— |
AE, adverse event; CRS, cytokine release syndrome; TEAE, treatment-emergent AE. *Data from Topp et al.1 |
The longer median OS and RFS are indicative of the greater benefit of blinatumomab as first salvage compared with second or later salvage. The safety profiles were similar across both groups except the incidence rate of serious treatment-emergent AEs, which was slightly higher among patients treated with second or later salvage. However, these findings should be considered in the context of some of the limitations of the study such as both groups were not well balanced in number and the impact of anti-CD22 monoclonal antibody was not evaluated.
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