Blood Cancer Awareness Month: Exploring Newer Therapies For Blood Cancers

Blood cancer, or hematologic malignancies, remains a significant global health concern, with over a million new cases diagnosed annually. The three primary types—leukaemia, lymphoma, and myeloma—originate in the bone marrow or lymphatic system, affecting the production and function of blood cells. Traditionally, treatments like chemotherapy, radiation therapy, and bone marrow transplants have been the cornerstones of blood cancer management. However, the landscape of therapy is rapidly evolving, with newer, more targeted treatments emerging, improving patient outcomes and quality of life.

This Blood Cancer Awareness Month, let us explore the latest advancements in blood cancer therapies, particularly those that leverage the immune system and molecular targets to fight the disease.

Immunotherapies

Immunotherapy has revolutionised the treatment of blood cancers by harnessing the body’s immune system to target and eliminate cancer cells. Several immunotherapy approaches have proven effective, including monoclonal antibodies, CAR T-cell therapy, and immune checkpoint inhibitors.

1. Monoclonal Antibodies: are laboratory-produced molecules engineered to target specific proteins on cancer cells. Once bound, they either directly kill the cancer cell or recruit immune cells to attack it. Some examples include:Rituximab which targets the CD20 protein on B-cells, used in treating Non-Hodgkin Lymphoma and chronic lymphocytic leukemia (CLL). Daratumumab is a monoclonal antibody targeting CD38, commonly used in the treatment of multiple myeloma.

2. Antibody Drug Conjugates: These are monoclonal antibodies tagged to a chemotherapeutic agent to target cancer cells effectively. An example is Brentuximab vedotin which is a CD30-directed antibody-drug conjugate used in relapsed or refractory Hodgkin lymphoma and Polatuzumab for B cell Non-Hodgkin’s Lymphoma. These therapies offer a more targeted approach than traditional chemotherapy, reducing collateral damage to healthy cells and often resulting in fewer side effects.

3. CAR T-cell Therapy: One of the most promising breakthroughs in blood cancer treatment is Chimeric Antigen Receptor (CAR) T-cell therapy. This innovative therapy involves collecting a patient’s T-cells, genetically modifying them to express a receptor specific to proteins on cancer cells, and then reintroducing these engineered T-cells into the patient. Once infused, the modified T-cells seek out and destroy cancer cells with remarkable precision.

CAR T-cell therapy has shown incredible success in treating relapsed or refractory acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL), often in patients who have exhausted other treatment options. These are also available as indigenous options (developed in India) which have made treatment more accessible to Indians and have changed the landscape for these high-risk patients. However, this therapy is not without challenges, including high costs, complex manufacturing processes, and potential side effects like cytokine release syndrome (CRS).

1. Immune Checkpoint Inhibitors: Checkpoint inhibitors have been groundbreaking in solid tumors, are now are making strides in blood cancers as well. These drugs block proteins such as PD-1 and CTLA-4, which cancer cells use to evade immune detection. By inhibiting these checkpoints, the immune system is unleashed to attack cancer cells more effectively.

Checkpoint inhibitors like Pembrolizumab and Nivolumab have shown promise in Hodgkin lymphoma, particularly in patients who have relapsed after standard treatments. While these drugs have demonstrated success, their role in other blood cancers is still under investigation.

1. BiTE therapy (Bispecific T-cell Engager therapy): is an emerging immunotherapeutic approach in cancer treatment, particularly for blood cancers. BITE molecules are designed to direct a patient's own T-cells to recognise and kill cancer cells by linking T-cells to specific proteins on cancer cells. An example is Blinatumomab used in ALL.

Targeted Therapies

Targeted therapies differ from traditional chemotherapy in that they specifically attack molecular changes driving the growth of cancer cells while sparing normal cells. The development of molecular diagnostics has allowed for the identification of specific mutations in blood cancers, leading to the advent of highly effective targeted treatments.

1)Tyrosine Kinase Inhibitors (TKIs) : A paradigm-shifting discovery in the treatment of chronic myeloid leukaemia (CML) was the development of tyrosine kinase inhibitors (TKIs), which target the BCR-ABL fusion protein resulting from the Philadelphia chromosome abnormality. The introduction of Imatinib (Gleevec) has turned CML from a deadly disease into a manageable chronic condition for many patients. Since then, newer, more potent TKIs such as Dasatinib, Nilotinib, and Bosutinib have been developed, offering alternatives for patients resistant to first-line therapy.

These are also effective in some acute lymphoblastic leukaemia (ALL) and other malignancies are driven by tyrosine kinase mutations, exemplifying how precision medicine can improve outcomes.

 2)BCL-2 Inhibitors: BCL-2 is a protein that helps cancer cells evade apoptosis (programmed cell death). Venetoclax a BCL-2 inhibitorsacts by inhibiting this protein and thus restores the cancer cell’s ability to undergo apoptosis. It has shown significant efficacy in treating chronic lymphocytic leukemia (CLL) and certain forms of acute myeloid leukaemia (AML).

3)Epigenetic Therapies: Epigenetic changes are chemical modifications that alter gene expression without changing the DNA sequence and thus play a critical role in the development of many blood cancers. Drugs that target these epigenetic modifications are becoming increasingly important in the treatment of blood cancers, particularly acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Examples include Hypomethylating agents like Azacitidine and Decitabine used for AML/ MDS. Histone Deacetylase (HDAC) Inhibitors such as Vorinostat and Romidepsin, modify the chromatin structure and gene expression in cancer cells, promoting cell cycle arrest and apoptosis. These agents have been particularly useful in the treatment of T-cell lymphomas.

Advances in Stem Cell Transplantation

Stem cell transplantation remains a key component in the treatment of many blood cancers, particularly in patients who relapse or do not respond to initial treatments. Advances in transplantation techniques, such as haploidentical transplants (using half-matched donors) and improved conditioning regimens, have expanded the availability of this potentially curative therapy to more patients. Moreover, the use of post-transplant maintenance therapies, such as immunomodulatory agents and TKIs, has helped reduce the risk of relapse after transplantation, further improving outcomes.

Blood cancers, once associated with a grim prognosis, are now being managed more effectively than ever before, thanks to these innovative therapies. Immunotherapies, targeted agents, epigenetic drugs, and improved transplant techniques have transformed the treatment landscape, offering new hope to patients with previously untreatable or relapsed diseases.

As we continue to observe Blood Cancer Awareness Month, it is crucial to recognise that while significant progress has been made, there remains much work to be done. Ongoing research and clinical trials are essential to expanding the therapeutic arsenal, reducing side effects, and improving long-term outcomes for patients with blood cancers. Blood cancer research is a testament to the power of innovation, and the future looks promisingly brighter.

Dr. Niti Krishna Raizada

Guest Author