Acute lymphoblastic leukaemia

The EU has approved 18 indications of 8 drugs in acute lymphoblastic leukaemia. 15 of them need a biomarker result: BCR::ABL1 (7), CD19 (6) and CD22 (2).

Approved indications, Acute lymphoblastic leukaemia
Drug	Biomarker requirement	Regimen	Setting	Conditions

BCR::ABL17
Dasatinib Sprycel, Dasatinib Accord Healthcare		+ chemotherapy	1L	Children and adolescents only
Imatinib Glivec	Philadelphia chromosome (bcr-abl)	+ chemotherapy	1L	None
Ponatinib Iclusig	Philadelphia chromosome (BCR::ABL1 translocation)	+ reduced-intensity chemotherapy	1L	None
Dasatinib Sprycel, Dasatinib Accord Healthcare		Monotherapy	2L	Resistance or intolerance to prior therapy
Imatinib Glivec	Philadelphia chromosome (bcr-abl)	Monotherapy	2L	Relapsed or refractory disease
Ponatinib Iclusig	Philadelphia chromosome (BCR::ABL1 translocation)	Monotherapy	2L	Resistant to dasatinib, or intolerant to dasatinib and subsequent treatment with imatinib is not clinically appropriate
Ponatinib Iclusig	T315I, Philadelphia chromosome-positive	Monotherapy	Any line	None

CD19-positive6
Blinatumomab Blincyto	Philadelphia chromosome-negative	Monotherapy	1L	B-cell precursor ALL only; In first or second complete remission with minimal residual disease (MRD) ≥ 0.1%
Blinatumomab Blincyto	Philadelphia chromosome-negative	Monotherapy	Consol.	B-cell precursor ALL only; Children and adolescents only; Aged 1 month or older; high-risk
Blinatumomab Blincyto	Philadelphia chromosome-negative	Monotherapy	Consol.	B-cell precursor ALL only
Blinatumomab Blincyto	Philadelphia chromosome-negative	Monotherapy	2L	B-cell precursor ALL only
Blinatumomab Blincyto	Philadelphia chromosome-negative	Monotherapy	2L	B-cell precursor ALL only; Children and adolescents only; After at least two prior therapies, or prior allogeneic haematopoietic stem cell transplantation; Aged 1 month or older
Blinatumomab Blincyto	Philadelphia chromosome-positive	Monotherapy	3L+	B-cell precursor ALL only; Failed treatment with at least 2 tyrosine kinase inhibitors (TKIs); No alternative treatment options

CD22-positive2
Inotuzumab ozogamicin Besponsa		Monotherapy	2L	B-cell precursor ALL only; Relapsed or refractory disease; patients with Ph+ disease should have failed treatment with at least 1 TKI
Inotuzumab ozogamicin Besponsa		Monotherapy	2L	B-cell precursor ALL only; Children and adolescents only; In first relapse after allo-HSCT, or after any first relapse in VHR disease, or after a second or greater relapse, or refractory disease; patients with Ph+ disease should have exhausted relevant BCR-ABL targeting treatment options; Aged 1 year and older

No biomarker required3
Brexucabtagene autoleucel Tecartusconditional	None	Monotherapy	2L	B-cell precursor ALL only; 26 years of age and above
Obecabtagene autoleucel Aucatzylconditional	None	Monotherapy	2L	B-cell precursor ALL only; Relapsed or refractory disease; 26 years of age and above
Tisagenlecleucel Kymriah	None	Monotherapy	2L	B-cell precursor ALL only; Refractory, in relapse post-transplant or in second or later relapse; Up to and including 25 years of age

Biomarkers in acute lymphoblastic leukaemia

Label wording18

The sentence from section 4.1 of the SmPC that each indication above comes from.

Imatinib (Glivec)
adult and paediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy.
Imatinib (Glivec)
adult patients with relapsed or refractory Ph+ ALL as monotherapy.
Dasatinib (Sprycel, Dasatinib Accord Healthcare)
Ph+ acute lymphoblastic leukaemia (ALL) and lymphoid blast CML with resistance or intolerance to prior therapy.
Dasatinib (Sprycel, Dasatinib Accord Healthcare)
newly diagnosed Ph+ ALL in combination with chemotherapy.
Blinatumomab (Blincyto)
BLINCYTO is indicated as monotherapy for the treatment of adults with CD19 positive relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL).
Blinatumomab (Blincyto)
BLINCYTO is indicated as monotherapy for the treatment of adults with CD19 positive relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL). Patients with Philadelphia chromosome-positive B-cell precursor ALL should have failed treatment with at least 2 tyrosine kinase inhibitors (TKIs) and have no alternative treatment options.
Blinatumomab (Blincyto)
BLINCYTO is indicated as monotherapy for the treatment of adults with Philadelphia chromosome-negative CD19 positive B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%.
Blinatumomab (Blincyto)
BLINCYTO is indicated as monotherapy for the treatment of paediatric patients aged 1 month or older with Philadelphia chromosome-negative CD19 positive B-cell precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic haematopoietic stem cell transplantation.
Blinatumomab (Blincyto)
BLINCYTO is indicated as monotherapy for the treatment of paediatric patients aged 1 month or older with high-risk first relapsed Philadelphia chromosome-negative CD19 positive B-cell precursor ALL as part of the consolidation therapy (see section 4.2).
Blinatumomab (Blincyto)
BLINCYTO is indicated as monotherapy as part of consolidation therapy for the treatment of adult patients with newly diagnosed Philadelphia chromosome negative CD19 positive B-cell precursor ALL.
Tisagenlecleucel (Kymriah)
Paediatric and young adult patients up to and including 25 years of age with B-cell acute lymphoblastic leukaemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse.
Ponatinib (Iclusig)
Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.
Ponatinib (Iclusig)
Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.
Ponatinib (Iclusig)
Iclusig is indicated in combination with reduced-intensity chemotherapy in adult patients with newly diagnosed Ph+ ALL (see section 5.1).
Brexucabtagene autoleucel (Tecartus)
Tecartus is indicated for the treatment of adult patients 26 years of age and above with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL).
Inotuzumab ozogamicin (Besponsa)
BESPONSA is indicated as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL). Patients with Philadelphia chromosome positive (Ph+) relapsed or refractory B-cell precursor ALL should have failed treatment with at least 1 tyrosine kinase inhibitor (TKI).
Inotuzumab ozogamicin (Besponsa)
BESPONSA is indicated as monotherapy for paediatric patients 1 year and older with CD22-positive B-cell precursor ALL: in first relapse after allo-haematopoietic stem cell transplant (HSCT); after any first relapse in patients with Very High Risk (VHR) disease (see section 5.1); after a second or greater relapse; and in those with refractory disease. Patients with Philadelphia chromosome positive (Ph+) disease should have exhausted relevant BCR-ABL targeting treatment options.
Obecabtagene autoleucel (Aucatzyl)
Aucatzyl is indicated for the treatment of adult patients 26 years of age and above with relapsed or refractory (r/r) B cell precursor acute lymphoblastic leukaemia (B ALL).