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
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