Combination of venetoclax and azacitidine in relapsed/refractory acute B-cell lymphoblastic leukemia: a case series from a single center

Figures & data

Table 1. Baseline of patients.

Characteristics	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6	Patient 7	Patient 8
Age(y)	46	57	44	59	16	39	40	52
Sex	Male	Male	Male	Female	Male	Male	Male	Female
WBC (_x109/L)	57.3	1.7	229.3	253	1.59	6.21	23.3	2.49
Hb (g/L)	132	50	85	106	100	135	97	129
PLT (_x109 /L)	22	30	57	61	55	11	34	158
Blast proportion in bone marrow (%)	15	94.5	60	87.5	96	94	83.6	75
Immunophenotype	B-ALL	B-ALL	B-ALL	B-ALL	B-ALL	B-ALL	B-ALL	B-ALL
Karyotype	46,XY,t(9;22)(q34;q11.2)[4]/46,XY[16]	46,XY[20]	47,XY,t(9;22)(q34;q11), der(16)t(1;16)[6]/46,XY[4]	46,XX[20]	46,XY,6q-,dup(8)(q22;q24)[7]/46,XY[13]	46,XY,i(9)(q10)[4]/ 46,idem,del(9)(p13;p24)[1]/ 46,XY[5]	46,XY[20]	46,XX[20]
Fusion gene	BCR::ABL(e14a2)	BCR::ABL(e1a2)	BCR::ABL(e1a2)	KMT2a::AFF1	Negative	Negative	Negative	Negative
Molecular abnormality	E255 V SNV	Negative	IKZF1-IK6 CNV	Negative	ETV6 SNV	BCL-6 CNV、SMC-2 CNV	(IKZF1-IK6 CNV、JAK2 SNV、KMT2D SNV)	JAK3 CNV、IDH1 CNV
Initial induction regimens (courses)/result (duration)	Dasatinib + DOP(1)/CR	IVP(1)/CR	Ara-C + DXM(1)/NR	IVLP(1)/CR	CIVP(1)/CR	IVP(1)/NR	Hyper-CVAD A (1)/NR	CIVP(1)/CR
Disease status before reinduction by VEN + AZA regimen(times of relapse)	Relapse(2)	Relapse(4)	Relapse(3)	Relapse(2)	Relapse(2)	Relapse(3)	Refractory	Relapse(2)
ECOG score prior to treatment	3	3	2	2	2	2	2	2
Fusion gene before reinduction by VEN + AZA regimen	BCR::ABL(e14a2):46.37%	BCR::ABL(e1a2):83.88%	BCR::ABL(e1a2):4.51%	KMT2a::AFF1:35.13%	ETV6:93%	BCL-6:18.2%;SMC-2:21%	__	JAK3(+)
Fusion gene after reinduction by VEN + AZA regimen	0.42%	0.58%	0.24%	7.63%	NA	NA	__	NA
Combination treatment during VEN + AZA regimen	Dasatinib	Ponatinib	Ponatinib	No	Selinexor	Bortezomib	No	No
Response of reinduction by VEN + AZA regimen/result/MRD	1/CR/3.1X10-4	1/CR/＜1.0X10-4	1/CR/1.4X10-4	1/PR/6.6%	1/CR/1.9X10-4	1/NR/50%	1/NR/93.9%	1/CR/1.9X10-4
CAR-T	Yes, prior to regimen	No	No	No	Yes, prior to regimen	Yes, prior to regimen	No	No
Transplanted	Yes, prior to regimen	No	Yes, prior to regimen	No	Yes, prior to regimen	Yes, prior to regimen	No	No

CNVs: copy number variations.

SNV: single nucleotide variation.

ECOG: Eastern Cooperative Oncology Group performance.

Figure 1. Summary of treatment response. (A) Minimal Residual Disease measured by flow cytometry. (B) Leukemia-associated fusion genes measured by real-time quantitative PCR.

Table 2. Response rates for patients who received ven/aza.

Response	N(%)
CR	3 (37.5)
CRi	2 (25.0)
MRD(-)	1 (12.5%)
ORR(CR + CRi)	5 (62.5%)

ORR = overall response rate, CR = complete remission, CRi = CR with incomplete hematologic recovery, MRD(-) = minimal residual disease negative by flow cytometry at the time of response, DOR = CR/CRi duration of response, OS = overall survival.

Table 3. Treatment-emergent adverse events.

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6	Patient 7	Patient 8
Anemia/grade	Yes/grade 3	Yes/grade 3	No	Yes/grade 2	Yes/grade 3	Yes/grade 1	Yes/grade 3	Yes/grade 2
agranulocytosis/duration	Yes/21d	Yes/7d	No	No	Yes/24d	Yes/9d	Yes/24d	No
Febrile neutropenia	Yes	No	No	No	Yes	Yes	Yes	No
Thrombocytopenia/grade	Yes/grade 4	Yes/grade 4	No	No	Yes/grade 4	Yes/grade 4	Yes/grade 4	No
Other toxicities/grade	Pneumonitis/grade 2	No	No	Pneumonitis/grade 2	Pneumonitis/grade 2	Renal disfunction/grade 2	Acute tonsillitis/grade 3	No
Follow-up and outcome	In continuous CR for 2 months then dead for pneumorrhagia	In continuous CR for 5 months then dead for cardiac failure	In continuous CR for 7 months till now under consolidation therapy	Preparing for CAR-T	Bridged to CD22-38 CAR-T but suffered severe infection, then dead	Suggest immunotherapy or second transplant, but patients refuse	Died after 2 month	In continuous CR for 2 months till now under consolidation therapy

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.