Page 140 - 2021_10-Haematologica-web

P. Strati et al.
Methods
Patient selection and evaluation
This is a post-hoc analysis of patients with refractory LBCL treat- ed with axi-cel on the pivotal ZUMA-1 study (clinicaltrials gov. Identfier: NCT02348216; n=24) or ZUMA-9 (clinicaltrials gov. Identfier: NCT03153462; n=7); the latter was an expanded access trial for patients not eligible for ZUMA-1 study (cohort 1) or whose commercial product was out-of-specification (OOS) (cohort 2), and two patients from cohort 2 were included in this analysis. Patients were treated at MD Anderson Cancer Center between 01/2015 and 03/2018 (data cut-off: 12/19/2018). The studies were approved by the Institutional Review Board and con- ducted in accordance with institutional guidelines and the princi- ples of the Declaration of Helsinki.
Conditioning chemotherapy and axi-cel infusion were adminis- tered as previously described.1,2 Clinical and laboratory features were collected prospectively in all patients who had a complete blood count (CBC) performed 30 days (+/- 5 days) after axi-cel infusion. Pre-conditioning laboratory values were available for CBC but not for lymphocyte subsets. Patients who received treat- ment and/or died for progression before day 30 were excluded. Infectious complications and diagnosis of MDS were reported from axi-cel infusion until last follow-up, progression, subsequent therapy or death. CRS and neurotoxicity were prospectively grad-
ed according to Lee 2014 criteria and CTCTAE v4.03, respectively.11 Response status was determined by 2007 revised response criteria for malignant lymphoma.12
Hematopoietic recovery and immune reconstitution assessment
In order to assess blood count and immune recovery, we per- formed CBC, lymphocyte subsets analysis by flow cytometry, and immunoglobulin G (IgG) levels at months 1, 3, 6, 9, 12, 15, 18 and 24, or until disease progression.
Statistical analysis
Categorical and continuous variables were evaluated using Chi square (χ2) or Fisher exact tests, or the Mann-Whitney test, as appropriate, to describe differences in baseline characteristics, response and toxicity between patients groups. Association between continuous variables were assessed using the bivariate Pearson correlation. A P-value of ≤0.05 (two-tailed) was consid- ered statistically significant (IBM SPSS 23).
Results
Patient baseline characteristics
Grade 3-4 cytopenias were observed in 15 (48%) of 31
Table 1. Baseline (day -5) characteristics by grade 3-4 cytopenia at day 30 after axi-cel infusion.
Total Grade 3-4 cytopenia No Grade 3-4 cytopenia (N=31) at 30 days (N=15) at 30 days (N=16)
N(%) N(%) N(%)
P-value
DLBCL PMBCL TFL
Age in years, median (range)
Male Female
ECOG 0 1
Ann Arbor Stage I-II III-IV
No BM involvement BM involvement
IPI score 0-2 3-4
Previous therapies (n)
> 3 previous therapies
Refractory disease
Previous ASCT
Cytopenia at day -5
ANC (109/L), median (range)
AMC (109/L), median (range)
ALC (109/L), median (range) Hemoglobin (g/dL), median (range) PLT count (109/L), median (range) Ferritin (ng/mL), median (range) CRP (mg/L), median (range)
LDH (U/L), median (range)
21 (68) 6 (19) 4 (13)
52 [23-76]
23 (74) 8 (26)
19 (61) 12 (39)
7 (23) 24 (77)
28 (90) 3 (10)
18 (58) 13 (42)
3 [1-11]
14 (45)
30 (97)
11 (35)
4 (13)
4 [0.8-24.8]
0.5 [0.1-1.6]
0.5 [0.2-3.6]
10.9 [7.4-14.2]
157 [31-409]
747 [209-9388]
51 [2.7-352]
703 [362-3426]
12 (80) 2 (13) 1 (7)
58 [23-76]
9 (60) 6 (40)
6 (40) 9 (60)
2 (13) 13 (87)
13 (87) 2 (13)
6 (40) 9 (60)
4 [2-8]
10 (67)
15 (100)
8 (53)
3 (20)
4 [1.1-24.9] 0.5 [0.1-1.2] 0.4 [0.2-3.6] 10.7 [7.4-12.6] 105 [31-356] 2205 [230-9388] 62.3 [2.7-352] 703 [362-3426]
9 (56) 0.35 4 (25)
3 (19)
51 [28-75] 0.86
14 (88) 0.11 2 (12)
13 (81) 0.03 3 (19)
5 (48) 0.39 11 (52)
15 (94) 0.60 1 (6)
12 (75) 0.07 4 (25)
3 [1-11] 0.05 4 (25) 0.03
15 (94) 1 3 (19) 0.07 1 (6) 0.33 3.8 [0.8-12] 0.86 0.5 [0.3-1.6] 0.72
0.7 [0.2-1.6] 0.007 11.3 [9.3-14.2] 0.10 184 [67-409] 0.21 450 [209-1554] 0.08
39.3 [3-268] 1 681 [369-1667] 1
DLBCL: diffuse large B-cell lymphoma; PMBCL: primary mediastinal B-cell lymphoma; TFL: transformed follicular lymphoma; BM: bone marrow; IPI: international prognostic index; n: number; ASCT: autologous stem cell transplant; ANC: absolute neutrophil count; AMC: absolute monocyte count; ALC: absolute lymphocyte count; PLT: platelet; CRP: C- reactive protein; LDH: lactate dehydrogenase.
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haematologica | 2021; 106(10)