Latest advances and outcomes from the treatment of acute leukemia today

Leukemia is a blood cancer that can be identified by the rapid growth of defective

blood cells. The marrow of our bone produces most of the blood in our body which is

the site of this abnormal growth. Typically, leukemia cells are immature white blood

cells. Leukemic cells alter the normal blood cell formation process, leading to various

signs and symptoms such as bleeding, infection, and tiredness.

There are two kinds of leukemia: acute leukemia and chronic leukemia. Further, the

acute type was classified into acute myeloid leukaemia (AML) and acute

lymphoblastic leukaemia (ALL). Myeloblasts, or defective white blood cells, are the

cause of acute myeloid leukaemia (AML). Acute myelogenous, granulocytic,

nonlymphocytic, or myeloblastic leukaemia are other terms for this kind of cancer.

However, the overproduction of lymphocytes is caused by acute lymphoblastic

leukaemia (ALL).

Stem cell transplantation, radiation therapy, and chemotherapy have been the

cornerstones of leukaemia treatment. Targeted therapy has also been included in the

standard of care for certain kinds of leukaemia within the past 20 years. These

medications target the proteins that regulate the growth, division, and metastasis of

cancer cells. Different treatment combinations are needed for different forms of

leukaemia.

For Acute lymphocytic leukemia (ALL), Immunotherapies are being used where

many elderly people are unable to handle the severe side effects of the intense

chemotherapy therapies required to treat ALL. Compared to chemotherapy, targeted

therapies might have fewer adverse effects.

Immunotherapies are treatments that enhance the body's ability to fight cancer

through the immune system. Currently, four immunotherapies are FDA approved for

the treatment of ALL: blinatumomab, inotuzumab ozogamicin, tisagenlecleucel and

midostaurin. In ALL, the following immunotherapy techniques are being tested or

employed are CAR T-cell therapy and bispecific T-cell engagers (BiTEs). A sort of

cancer treatment called CAR T-cell therapy involves genetically modifying the

patient & own immune cells. For the treatment of some children and young adults with

ALL, one kind of CAR T cell therapy is currently approved. Dosing is based on

weight reported at the time of leukapheresis.The use of this type in elderly B-cell

ALL patients is now being investigated. Adults with B-cell precursor ALL who have

not responded to previous treatment or have returned after treatment have been

approved for another course of CAR T-cell therapy.

Bispecific T-cell engagers (BiTEs) are another immunotherapy that is being studied

for ALL. These medications bind to both cancer and immune cells, drawing the two

groups of cells closer together so that the immune cells can locate and eliminate the

cancer cells with ease. Recently, it was demonstrated that one such BiTE,

blinatumomab, can increase survival for ALL patients in remission following

chemotherapy, even in situations where the disease is completely eradicated.

Acute myeloid leukaemia (AML) tends to be aggressive and was harder to treat than

ALL. However, AML cells sometimes have gene changes that cause the tumors to

grow but can be targeted with new drugs. The management of AML involves two

phases such as remission induction therapy (first phase of treatment to kill

the  leukemia   cells  in the blood and  bone marrow ) and remission continuation therapy

(second phase of treatment to kill any remaining leukemia cells).

The treatment of AML includes chemotherapy (drugs to stop the growth of cancer

cells), radiation therapy (uses high-energy  x-rays  or other types of  radiation  to kill

cancer cells), stem cell transplant (to replace the blood-forming cells from the blood

or  bone marrow  of the patient) and targeted therapy (drugs or other substances to

identify and attack specific cancer cells) or combination of both. Targeted treatments

such as Enasidenib, Olutasidenib, Ivosidenib, Venetoclax, Gemtuzumab ozogamicin,

Midostaurin, Gilteritinib, Glasdegib, and Quizartinib have recently been approved to

treat AML with specific gene alterations.

In order to achieve complete remission (CR) from acute leukaemia, standard

treatment paradigms have involved high-intensity induction chemotherapy. In certain

cases, this was followed by an allogeneic hematopoietic cell transplant (allo-HCT) to

eliminate residual disease through the "graft versus leukaemia effect, which is

mediated by the immune cells of the donor. Allo-HCT is not recommended for all

patients, though, and one of the biggest problems facing the industry at the moment is

the lack of viable chemotherapy-based choices for patients who relapse after allo-

HCT or who develop chemotherapy-refractory illness.

The potential of immunotherapy in the treatment of acute myeloid leukaemia (AML)

has been established by the effectiveness of allogeneic stem cell transplantation.

Alternative T-cell-based immunotherapies have demonstrated effectiveness, but there

is a chance that they could cause on-target off-leukemia hematotoxicity. Currently,

the use of adoptive autologous or allogeneic chimeric antigen receptor (CAR) T /

natural killer cell treatment as a bridge-to-transplant approach is almost only available

in clinical studies.

Acute leukaemia used to be nearly always fatal, but now it has a 63% 5-year survival

rate in the US. The therapeutic options for acute leukaemia have increased with the

introduction of immunotherapy, however, the advancement in AML has been slower.

Novel medicines such as ADCs, CAR T cell treatments, and BiTEs continue to show

remarkable response rates and favourable toxicity profiles in various disease states

every year. Even with these developments, a large number of patients are still not

eligible for immunotherapeutic treatments, and relapses following some of the more

recent modalities are still linked to extremely poor prognoses. In the future, new

medicines with potentially unique mechanisms of action will probably be approved

together with the expansion of the indications for currently available medications.

References:

1. Leukemia. National Cancer Institute. Available at:

https://www.cancer.gov/types/leukemia/hp/adult-aml-treatment-pdq

2. Boyiadzis MM, Aksentijevich I, Arber DA, et al. The Society for Immunotherapy

of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of

acute leukemia. Journal for ImmunoTherapy of Cancer. 2020

3. Kantarjian, H., Kadia, T., DiNardo, C. et al. Acute myeloid leukemia: current

progress and future directions. Blood Cancer J. 2021

4. Subklewe M, Bücklein V, Sallman D, Daver N. Novel immunotherapies in the

treatment of AML: is there hope? Hematology Am Soc Hematol Educ Program. 2023

Dec 8;2023