CAR-T Cell Therapy for Lymphoma

A lymphocyte as seen in light microscopy, artistic rendition.

CAR-T cell therapy is a new, research-stage cancer treatment that involves engineering your own immune cells to recognize and attack the cancer cells.

The engineered cells are called CAR-T cells. Though it is still a research therapy, it is generating great interest.

What Does CAR-T Stand For?

The T-cell part of the name is the easy part: T-cells are the immune system’s “soldier cells” that go out to fight the invaders that the immune "intelligence community" has identified.

T-cells can also attack cancer cells, but only if they are able to recognize them as such.

Now for the CAR part of the name: CAR stands for chimeric antigen receptors. A chimera was a monster from Greek mythology -- a combo-creature that breathed fire and had a lion's head, a goat's body, and a snake's tail… or something like that. The point, as it relates to a chimeric antigen receptor, is that a CAR is genetically engineered or re-built using bits and pieces from different sources -- a patch-work of materials -- to create a modified T-cell that can, for the very first time, recognize the elusive cancer cells as foreign.

So, once in the laboratory, your T-cells are modified to produce special CARs on their surface that can bind to surface proteins or tags on cancer cells. The CAR-T cells are then grown, allowed to become numerous and then reintroduced into the patient.

CAR-T Cell Therapy… for Lymphoma

Lymphomas are malignancies of the lymphoid tissues, including lymphocytes—a type of white blood cell.

There are B-lymphocytes and T-lymphocytes, or B-cells and T-cells, for short.

Updated findings from early-stage trials of CAR T-cell therapies continue to show promising results in non-Hodgkin lymphoma (NHL), the most common category of lymphoma. In his coverage of the 2015 Annual Society of Hematology (ASH) meeting, Silas Inman of OncLive reported on preliminary findings from two CAR-T cell studies involving patients with a variety of different NHL types.

The first study used CAR T-cells built to recognize CD19 – a tag, or antigen, on the outside of B-cells. Two very common non-Hodgkin lymphoma types that arise from B-lymphocytes are diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma.

In this study, there was an overall response rate of 73 percent in people with follicular lymphoma and 47 percent in those with DLBCL. Most of the partial responses that were seen at 3 months became complete remissions after 6 months of follow-up.

This study enrolled 43 patients: 26 with DLBCL, 14 with follicular lymphoma, and 3 with mantle cell lymphoma, which is also a B-cell lymphoma. Out of those enrolled, 13 were not given CAR-T therapy, and in 6 of these cases, it was because CAR-T cell production had failed. The most common serious, or grade 3, adverse events related to depletion of white blood cells, red blood cells and platelets that help clotting.

The second study also involved CAR T-cells built to recognize the CD19 tag, this study also included something called lymphodepletion, or the destruction of lymphocytes and T cells in advance.

Some 30 patients with NHL and 9 patients with chronic lymphocytic leukemia were included for analysis. Because this was an early study, investigators aimed to lay down some important groundwork -- to understand how the dose of CAR T-cell therapy relates to efficacy and toxicity, and also to identify measurements or markers that will be important to watch, going forward.

Without lymphodepletion, accross all tested doses, the complete response rate was 8 percent. In patients with chronic lymphocytic leukemia (CLL), the overall response rate with the CAR-T cells plus fludarabine and cyclophosphamide (for lymphodepletion) was 100 percent. The complete response rate in this group was 57 percent. Severe neurotoxicity was seen in 33 percent, 18 percent, and 67 percent of patients treated with dose 1, 2, and 3, respectively. In the non-lymphodepletion group, the neurotoxicity rate was 17 percent.

Cytokine release syndrome, or CRS, is associated with CAR-T cell therapies and is a potential source of toxicity -- the syndrome ranges from mild to life threatening. At the highest doses, in this second study, the rate of severe CRS was 50 percent. CRS refers to the effects from a flood of cell signals, or cytokines, that may come in the process of revving up the immune response; in most patients, CRS symptoms are mild and flu-like, with fevers and muscle aches. However, some patients with CRS experience a severe inflammatory syndrome, which can lead to multi-organ failure.

CAR-T on the Horizon

According to the coverage by OncLive, “a number of clinical trials continue to assess novel CAR T-cell therapies for patients with NHL. In addition to the therapies manufactured by Juno and Novartis, a host of other companies are exploring this treatment approach. At this time, none of these therapies have gained FDA approval. However, some analysts project a regulatory decision as soon as 2017.”


CAR T-Cell Therapy: Engineering Patients’ Immune Cells to Treat Their Cancers. Accessed December 2015.

Barrett DM, Singh N, Porter DL, Grupp SA, June CH. Chimeric Antigen Receptor Therapy for Cancer. Annu Rev Med. 2014;65:333-347.

Chimeric Antigen Receptor T-Cells. Accessed December 2015.

Schuster SJ, Svoboda J, Nasta SD, et al. Sustained Remissions Following Chimeric Antigen Receptor Modified T Cells Directed Against CD19 (CTL019) in Patients with Relapsed or Refractory CD19+ Lymphomas. Presented at: 57th American Society of Hematology Annual Meeting; Orlando, Florida; December 5-8, 2015. Abstract 183.

Turtle CJ, Berger C, Sommermeyer D, et al. Anti-CD19 Chimeric Antigen Receptor-Modified T Cell Therapy for B Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Fludarabine and Cyclophosphamide Lymphodepletion Improves In Vivo Expansion and Persistence of CAR-T Cells and Clinical Outcomes. Presented at: 57th American Society of Hematology Annual Meeting; Orlando, Florida; December 5-8, 2015. Abstract 184.

The Leukemia and Lymphoma Society. Chimeric Antigen Receptor (CAR) T-Cell Therapy. Accessed December 2015.

Maude SL, Barrett D, Teachey DT, Grupp SA. Managing Cytokine Release Syndrome Associated With Novel T Cell-Engaging Therapies. Cancer journal (Sudbury, Mass). 2014;20(2):119-122.

Continue Reading