Loncastuximab Tesirine-lpyl Therapy: Diffuse Large B-Cell Lymphoma


Loncastuximab tesirine-lpyl just got accelerated approval from the U.S. Food and Drug Administration (FDA). This is a systemic therapy for people with diffuse large B-cell lymphoma (DLBCL). 

Under the brand name Zynlonta, the loncastuximab tesirine-lpyl is an antibody drug that targets protein CD19 to attack B-cell hematological tumors.

After targeting and binding the tumor cells to CD19, the cytotoxic pyrrolobenzodiazepine dimers (PBD), which have antibacterial and anti-tumor properties, become responsible for killing the cancer cells, specifically those seen in DLBCL. 

RELATED: AACR: BMS Checkpoint Inhibitor Flexes Muscle in Early-Stage Lung Cancer and Other Highlights

What Is B-Cell Lymphoma? 

B-cell lymphoma is cancer forming in the white blood cells called lymphocytes. It causes your body to produce too many abnormal B cells. These cells can be harmful because they can’t fight off infections because of the abnormalities. These then spread to different parts of a person’s body, causing more harm.

B-cell lymphomas are classified into two categories: Hodgkin’s lymphoma and the more common non-Hodgkin lymphoma.

Hodgkin’s lymphoma (HL) is the type that affects the lymphatic system of a person -- most commonly seen in lymph nodes. The presence of Reed-Sternberg cells characterizes HL.

Non-Hodgkin lymphoma also affects the lymph nodes, but is characterized by it spreading to other parts of the lymphatic system. 

Unfortunately, non-Hodgkin lymphoma, even though it is more common, tends to be less treatable than HL, with the latter recording a 90% chance of surviving for more than five years of having it.

There are several types of B-cell lymphoma. Here are some common ones:

  • Follicular lymphoma: This is focused mostly on older adults and is a slow-growing form of this condition.

  • Chronic lymphocytic leukemia: This progresses more aggressively than other types, and it attacks the bone marrow. This is the condition where the bone marrow produces too many lymphocytes.

  • Mantle cell lymphoma: This is characterized as a fast-growing lymphoma.

  • Marginal zone lymphoma: This starts small and grows slowly.

  • Diffuse Large B-Cell Lymphoma (DLBCL): This attacks the immune system since it attacks the B-cells, which are responsible for producing antibodies.

What Is Diffuse Large B-Cell Lymphoma? Is It Curable?

Diffuse large B-cell lymphoma is a cancer of the B-cells. It is a type of lymphocyte, which is responsible for producing antibodies that fight infections.

This commonly occurs in patients over the age of 60, but some carry it through their childhood and develop them as they age.

DLBCL develops in lymph nodes and sometimes in extranodal sites like the thyroid, skin, breast, bone, brain, gastrointestinal tract or testes.

This type is the most common here in the United States, with more than 18,000 people diagnosed each year.

Even though DLBCL is considered to be an aggressive type of lymphoma, it can also be cured. The stage at which the cancer is detected is crucial to know if it is still curable.

Ways to treat this are through chemotherapy, radiation or immunotherapy. There are also new drugs and treatment plans being developed to fight off DLBCL.

RELATED: GenomeFrontier, Ziopharm Non-Viral Vectors Could Transform CAR-T Cell Therapy

What Causes B-Cell Lymphoma?

There is no direct cause of how B-cell lymphoma is developed in the body. It is just the abnormality of the white blood cells that trigger lymphocytes to grow out of control.

Even though acquiring this could happen by chance, there are risk factors involved that may lead to the development of this condition. The risk factors include age, autoimmune conditions, lowered immune system, certain infections or family history.

Having some of these factors doesn’t necessarily mean a person will develop lymphoma. However, it can increase the chance of having it.

What Is the Treatment For B-Cell Lymphoma?

A person with B-cell lymphoma can be treated through chemotherapy, immunotherapy or radiation. But treatment will depend on what type of lymphoma a person has, his/her age, overall health, symptoms, the location of cancer and how fast it is growing.

For those diagnosed at an early stage, some doctors might just observe the behavior of the cancer cells through frequent checkups without any plan of treating them yet. The reason behind this is to see the aggressiveness or lack thereof of the cancer cells to if it still needs to be treated if it won’t develop further. 

Chemotherapy is the most common way to treat most types of cancer. There are different ways chemo works, and it can be administered through IV (vein) or orally (pill). Some people receive it through cerebral spinal fluid, commonly used for cancer that has spread in their brain or spinal cord.

For B-cell lymphoma, the most common chemo routines are the R-CHOP, which stands for the drugs taken (Rituxan, Cytoxan, Hydroxydaunorubicin, Oncovin, and Prednisone).

Another common treatment is the CVP, which is taking Cyclophosphamide, Vincristine and Prednisone.

Recently, the Food and Drug Administration (FDA) approved Breyanzi (lisocabtagene maraleucel; liso-cel), which is from Bristol Myers Squibb (BMS), as systemic therapy for those with DLBCL. This is a chimeric antigen receptor T cell therapy that is directed to the CD19. This process includes the extraction of T cells from a patient, which is then engineered in a lab and then infused back to them to target and battle the cancer cells. This can be administered through outpatient options.

Loncastuximab Tesirine-lpyl FDA Approval

Another treatment for treating patients with DLBCL is Loncastuximab Tesirine-lpyl (Lonca) which recently got a green light from the DFA for accelerated approval. This drug is developed by ADC Therapeutics.

Loncastuximab tesirine-lpyl, an antibody-drug conjugate (ADC), consists of a humanized monoclonal antibody designed to target human CD19, a treatment target for B-cell malignancies. This process battles and kills a cancer cell by binding in the DNA using a “warhead” to disrupt a DNA metabolic process that can stop cancer production.

Early studies showed a 48.3% overall response rate, which was above the target rate of ADC. There was also a complete response (CR) rate of 24.1% and manageable toxicity.

The discovery of new treatments for diffuse large B-cell lymphoma, like the Loncastuximab Tesirinein-lpyl, helps bring us closer to the cure and treatment of cancer. 

Back to news