CAR T-cells for B cell lymphoma (Non-Hodgkin’s lymphoma) 

Lymphoma is cancer of the lymphatic system.  When a person develops lymphoma, their lymphocytes become abnormal cancerous cells and grow uncontrollably. This can cause your immune system to be compromised. As these cells move throughout the lymphatic system, they lodge into lymph nodes and cause them to swell. They also have the potential to cause harm to different organs in your body.

There are two main types of lymphoma: 

• Hodgkin’s lymphoma

• Non-Hodgkin’s Lymphoma (NHL)

Hodgkin’s lymphoma is treatable, especially in its early stages. Hodgkin’s lymphoma is a B-cell Lymphoma that arises from a Reed-Sternberg cell (named after the doctors who first discovered this cell). Hodgkin’s lymphoma is caused by a gene mutation in the growing white blood cells called B lymphocytes. These mutations are not inherited.  Hodgkin’s lymphoma begins in the lymph nodes of the neck or chest and then spreads from one part of the lymphatic system to another. In Hodgkin’s lymphoma, the tumors usually contain unique cells called Reed-Sternberg cells. 

The one-year survival rate for all patients diagnosed with Hodgkin’s lymphoma is about 92 percent. The five-year survival rate is about 86 percent. For people with stage 4 Hodgkin’s lymphoma, the survival rate is lower. But even in stage 4 you can beat the disease. Hodgkin’s Lymphoma is usually treated with Chemotherapy.

Non-Hodgkin’s lymphoma (also called Non-Hodgkin’s Lymphoma) is a disease in which cancer cells form in the lymphatic system and start to grow uncontrollably.

There are several different types of lymphomas. Some involve lymphoid cells (called Reed-Sternberg cells) and are grouped under the heading of Hodgkin’s lymphoma. All other forms of lymphoma fall into the non-Hodgkin’s grouping. The different forms of non-Hodgkin’s lymphoma are marked by the malignant growth of white blood cells that live in the lymph nodes, called lymphocytes.

Aggressive NHL (Non-Hodgkin’s Lymphoma) progresses quickly. According to the Leukemia and Lymphoma Society (LLS), about 60 percent of people with NHL have aggressive subtypes of the disease. Diffuse large B-cell Lymphoma (DLBCL) is the most common aggressive subtype. For stage IV NHL, the 5-year survival rate is around 63% which is much less than Hodgkin’s lymphoma. 

Relapsed or refractory (Not responding to treatment called R/R) diffuse large B-cell Lymphoma (DLBCL) is associated with a generally poor prognosis. Patients with R/R disease after frontline chemotherapy have a 3-year event-free survival of about 30%.  Even in fit patients with chemo sensitive disease to salvage therapy, only 50% will ultimately progress after autologous hematopoietic cell transplant (AHCT) and experience a median overall survival (OS) of 10 months.  Those who have disease refractory to primary or salvage chemotherapy or relapse in ≤12 months after AHCT have especially poor outcomes, with an overall response rate (ORR) of 26% to the next line of therapy and median OS of 6.3 months. These survival rates vary depending on the cancer's stage and subtype. It is important to remember that statistics on the survival rates for people with NHL are an estimate. 

Cellular immunotherapy with CAR T-cell has changed the treatment landscape of B-cell Non-Hodgkin’s Lymphoma (NHL), especially for aggressive B-cell Lymphomas. Single-center and multicenter clinical trials with CAR T-cell therapy have shown great activity and long-term remissions large B-cell Lymphoma (DLBCL- Diffuse large B-cell Lymphoma, or DLBCL, is a cancer that starts in white blood cells called lymphocytes) when no other effective treatment options are available.

A report from the National Cancer Institute in 2017 included 22 aggressive B-cell Lymphoma patients. In this study, a low-dose conditioning chemotherapy (cyclophosphamide 300–500 mg/m2 and fludarabine 30 mg for 3 days) was considered to have a lymphodepleting action and was associated with less hematologic and nonhematologic toxicity. The overall response rate (ORR) and CR (Complete Response) rates were 68% and 47%, respectively. The median duration of remission was 12.5 months and the 12-months progression-free survival (PFS) was 63.3%.

Another study form 2018 included 274 patients treated. The median time of CAR T-cell manufacturing was 21.5 days. General characteristics of the patients in the study included a median age of 60, stage 3&4 cancer in 83% of the patients. The overall efficacy was at 3-month Overall response rate (ORR) and CR rates of 81% and 57%, respectively. A 57% complete response rate is a promising outcome for most patients.

A second study from 2018, included 108 patients infused with CAR T-cells. The median age was 63.8 years. Of the 108 patients only 95 patients could be evaluated for response, the best ORR and CR rates were 71 and 44%, respectively. Similarly, about 50% of patients who initially had a Positive Response, achieved CR at a later time. 

CAR T-cells represent the new standard of care for patients with lymphoma that are refractory (fails to respond to treatment) to at least two prior lines of therapy. While this represents a significant addition to the treatment options of DLBCL, approximately 50% of cases will continue to succumb to their disease. As a result, future research must focus on identifying disease, treatment or patient-related factors that can help successfully predict treatment outcomes. 

CAR T-cells for B-cell Lymphoma (Non-Hodgkin’s lymphoma) 

• 39 B-cell Lymphoma patients have been treated by CAR-T

• 3-month best overall response rate is 79.5% (31/39);

• The first patient treated with this product achieved complete remission in the first 3 months and had a 24-month relapse free until today. 

The side effects of CAR T-cells vary with the type of treatment the patient uses. There are several large companies and a few smaller companies with differing technology.  The newer technologies have fewer side effects that the so-called first generation of CAR T-cells.

The most prominent side effect of CAR T-cell treatment is Cytokine-Release Syndrome (CRS). This potentially serious side effect is frequently associated with CAR T-cell therapy. Cytokines (chemical messengers that help the T cells carry out their functions) are produced when the CAR T-cells multiple in the body and kill the cancer cells. CRS symptoms can range from mild flulike symptoms that include.

• Nausea

• Fatigue

• Headache

• Chills

• Fever