A review of immunotargeted therapy for Philadelphia chromosome positive acute lymphoblastic leukaemia: making progress in chemotherapy-free regimens

Figures & data

Figure 1. Timeline of the development of PH + ALL targeted therapy. CML: chronic myeloid leukemia.

Table 1. Summary of ongoing or completed clinical trials for treating PH + ALL.

Clinical trials identifier	Trial phase	Status	Eligible ages	Intervention	Comments
NCT04329325	2	Recruiting	≥18 Years and older	Blinatumomab, Dasatinib, Dexamethasone, Methotrexate	Evaluating efficacy
NCT03147612	2	Recruiting	≥18 Years and older	Blinatumomab, Ponatinib, Chemotherapy	Evaluating efficacy
NCT03318770	Observ-ational Study	Recruiting	≥18 Years and older	Blinatumomab, Dasatinib	Evaluating safety and efficacy
NCT02997761	2	Recruiting	≥18 Years and older	Blinatumomab, Ibrutinib	Evaluating safety and efficacy
NCT06061094	2	Recruiting	18 - 65 Years	Blinatumomab, Dasatinib, Ponatinib	Evaluating safety and efficacy
NCT03984968	1/2	Recruiting	18 - 60 Years	CD19-CAR-T, Feeding T cells	Evaluating safety and efficacy
NCT03233854	1	Recruiting	≥18 Years and older	CD19/CD22-CAR-T, NKTR-255, Cyclophosphamide, Fludarabine Phosphate	Evaluating safety and efficacy
NCT04747912	2	Recruiting	≥18 Years and older	Inotuzumab Ozogamicin, Dasatinib, Ponatinib, Dexamethasone, Methotrexate, Vincristine	Evaluating efficacy
NCT02081378	1	Active	≥18 Years and older	ABL001, Nilotinib, Imatinib, Dasatinib	Evaluating safe and tolerated dose of ABL001
NCT05594784	2	Recruiting	≥14 Years and older	Venetoclax, Olverembatinib, Prednisone, Vincristine	Evaluating safety and efficacy
NCT02000427	2	Completed	≥18 Years and older	Blinatumomab	CR/CRh rate: 35.6% (n:16/45)
NCT00560794	2	Completed	≥18 Years and older	Blinatumomab	Incidence of MRD negativity within four cycles of treatment (n:3/5)
NCT01319981	2	Completed	≥18 Years and older	Rituximab, Imatinib, Chemotherapy	CR rate: H + C + R = 80% (12/15) H + C = 81.3% (13/16)
NCT00352677	1	Completed	≥18 Years and older	INNO-406	Evaluating safety and tolerability

CR/CRh: Complete remission/Complete remission with partial haematological recovery, Hyper-CVAD: hyper-fractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone, MRD: minimal residual disease

Table 2. Summary of TKIs-based treatment for PH + ALL.

Basic information	Interventions	Condition	N	Clinical outcomes	Reference
UMIN000001226 (phase 2)	Imatinib + CT	ND	68	CR = 95.6% (65/68) 3-y EFS: 52% 3-y OS: 62%	Fujisawa, [9]
NCT00287105 (phase 2)	Imatinib + CT	NA	155	CR = 97% (151/155)	Biondi, [10]
NCT00327678 (Phase 3)	A: Imatinib + low-intensity CT B: Imatinib + hyper-CVAD	ND	145	CR/EFS/OS A = 98%/42%/48% B = 91%/32%/43%	Chalandon, [4]
Retrospective analysis	Imatinib + CT	ND	153	CR = 96% (148/153) 3-y EFS = 49.2% 3-y OS = 49.5%	Lou, [11]
NCT00038610 (Phase 2)	Imatinib + hyper-CVAD	ND	45	CR = 93% (42/45)	Daver, [12]
NCT00618501 (phase 2)	Imatinib + CT	ND	87	CR = 94% (82/87)	Lim, [13]
ChiCTR-IPR-14005706 (phase 3)	Dasatinib vs Imatinib	ND	189	Dasatinib Imatinib 4-y EFS: 71%, 48% 4-y OS: 88%, 69%	Shen, [14]
UMIN000012173 (phase 2)	Dasatinib + CT	ND	78	CR + CRi = 100% 3-y EFS: 66.2% 3-y OS: 80.5%	Sugiura, [15]
NCT00720109 (Phase 2,3)	Dasatinib vs CT	ND	60	CR = 98% (59/60)	Slayton, [16]
NCT01256398 (Phase 2)	Dasatinib + Dexamethasone	NA	65	CR = 98.5% (64/65)	Wieduwilt, [17]
2006-005694-21	Dasatinib + low-intensity CT	ND	71	CR = 96% (67/71)	Rousselot, [18]
NCT00792948 (Phase 2)	Dasatinib + CT	ND	94	CR = 88% (83/94)	Ravandi, [19]
ChiCTR-ONC-12002469 (Phase 2)	Nilotinib + CT	ND	30	HCR = 100% 4-y HRFS: 54% 4-y OS: 45%	Liu, [20]
NCT00844298	Nilotinib + CT	ND	90	HCR = 91% (82/90)	Kim, [21]
NCT02776605 (phase 2)	Ponatinib + CT	ND	30	CR = 100% 3-y EFS: 70% 3-y OS: 96%	Ribera, [22]
NCT01424982	Ponatinib + hyper-CVAD	ND	76	CMR = 83% (63/76)	Jabbour, [23]
Propensity score analysis	Ponatinib + hyper-CVAD vs Dasatinib + hyper-CVAD	ND	41 vs 41	Po Da CR: 100% 95% 3-y EFS: 69% 46% 3-y OS: 83% 56%	Sasaki, [24]
Retrospective study	Hyper-CVAD + Ponatinib	ND	13	3-month CMR: 76.9% 3-y OS/EFS: 92.3%	Othman, [25]
NCT01207440 (phase 2)	Ponatinib	R/R	32	McyR: 47% (15/32)	Cortes, [26]
NCT01641107 (phase 2)	Ponatinib + Steroid	ND	44	CHR: 86.4% (38/44)	Martinelli, [27]
NCT03576547 (phase 1/2)	Ponatinib + Venetoclax + Dexamethasone	R/R	9	CR/CRi: 56% (5/9) 1-y OS: 72%	Short, [28]

ND: newly diagnosed, R/R: refractory/relapse, CT: chemotherapy, CMR: complete molecular response, HCR: haematologic complete remission, HRFS: haematologic relapse-free survival, CRi: incomplete haematologic recovery, DFS: disease-free survival, CHR: complete haematologic response,

Table 3. Summary of Immune-targeted therapy for PH + ALL.

Basic information	Interventions	Condition	N	Clinical outcomes	Reference
Case report	Venetoclax + Ponatinib or Flumatinib	R/R	5	CMR/CR = 80%	Yin, [76]
NCT03576547 (phase 1/2)	Venetoclax + Pobatinib	R/R	9	CRi/CR = 56% 1-year OS = 72%	Farhad, [28]
Retrospective study	Venetoclax + Pobatinib or Dasatinib +Dexamethasone	R/R	19	CRi/CR = 89.5%	Zhu, [77]
NCT02744768 (Phase 2)	Dasatinib + Blinatumomab	ND	63	2-cycles CMR: 60% OS: 95% DFS: 88%	Robin, [62]
NCT02458014 (phase 2)	Blinatumomab + Ponatinib or Dasatinib	MRD+	18	CMR = 61%	Elias J, [78]
NCT02000427 (phase 2)	Blinatumomab	R/R	45	CR/CRh = 35.6%	Giovanni, [79]
Retrospective study	Blinatumomab	R/R	34	CR/CRh/CRi = 41%	Nicolas, [80]
NCT03263572 (phase 2)	Blinatumomab + Ponatinib	ND R/R	60	CR = 87% 1-year OS = 95%	Prof, [81]
NCT02143414 (Phase 2)	Dasatinib + Prednisone+ Blinatumomab	ND	24	CR: 92% 3-y OS: 87% 3-y DFS: 77%	Advani, [40]
Case report	anti-CD19 CAR-T	R/R	7	CR = 6/7 CRq = 1/7	Qiu, [82]
Retrospective study	anti-CD19 CAR-T	R/R	18	CR = 100% 2-year OS = 88% 2-year RFS = 88%	Allison, [83]
NCT03825718 (Phase 1)	anti-CD19 CAR-T	R/R	24	CR = 2/25 CRi = 23/25	Yang, [84]
NCT03173417 (phase 1/2)	anti-CD19 CAR-T	R/R	14	CR = 100%	Zhang, [85]
NCT01319981 (Phase 2)	Rituximab + Imatinib or Dasatinib	ND	20	CMR = 70% MMR = 95%	Elias, [86]
NCT01085617 (Phase 3)	Rituximab + Imatinib + SOC	ND	86	CR = 97% 3-year OS = 59% 3-year EFS = 51%	Prof, [87]
NCT02311998 (phase 1/2)	Inotuzumab ozogamicin + Bosutinib	R/R	18	CR/CRi = 83%	Nitin, [88]
Phase 2 Study	Inotuzumab ozogamicin + Pobatinib or Dasatinib	MRD+	17	MRD- = 59% CR1 = 88%	Jayastu, [89]
NCT01363297 (phase 1/2) NCT01564784 (Phase 3)	Inotuzumab ozogamicin	R/R	22	CR/CRi = 73% MRD- = 81%	Wendy, [90]

CRp: complete remission with incomplete recovery of platelets

Figure 2. Mechanism of action of multiple targeted therapeutics in PH + ALL. CDC: complement-dependent cytotoxicity. ADCC: antibody-dependent cell-mediated cytotoxicity.

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