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Case Study: CAR T-Cell Therapy for Refractory DLBCL

  • Advances in Hematologic Malignancies banner Issue 7 Fall 2017
  • Advances in Hematologic Malignancies Issue 7, Fall 2017

    Caron Jacobson, MD

    After 2 years of watchful waiting for her follicular lymphoma, Judy, now aged 57, developed profound fatigue and hypercalcemia. A PET scan and a bone marrow biopsy later, she was found to now have diffuse large B-cell lymphoma (DLBCL). Over the ensuing 15-18 months, she was treated with three different chemotherapy regimens, all with a mixed response but ultimately progressive disease. Autologous stem cell transplant was off the table given her chemo-refractory disease, and she had been started on rituximab and lenalidomide. I had just introduced allogeneic stem cell transplant when a new option came along — chimeric antigen receptor T-cells, or CAR T-cells.

    Judy was apprehensive about the allogeneic transplant both because of the potential toxicities but more because of the year out of work it would mean. Judy is a self-employed hairdresser and that would mean a year without income. It was in the midst of this discussion that we learned of a slot on our clinical trial of an anti-CD19 directed CAR T-cell, KTE-C19 or axi-cel, in refractory DLBCL, transformed follicular lymphoma, or primary mediastinal B-cell lymphoma.

    CAR T-cells are genetically modified T-cells from the patient themselves. The T-cells are removed from the patient’s blood and are then engineered in a laboratory so that new DNA is added to the T-cells. This DNA codes for the chimeric antigen receptor (CAR), a protein that will eventually be displayed on the surface of the T-cell. This protein does two things: 1) it recognizes a protein, or antigen, on the tumor cell (in this case CD19), and 2) it contains activating and costimulatory molecules to activate the T-cell upon antigen binding (see Figure 1 below). The end result is an immune attack on the tumor cell once the T-cells are reinfused into the patient. This technology is the most advanced and efficacious when directed against CD19 in B-cell malignancies for the moment, but other tumor antigens in other cancers are being tested, as well.

  • CAR T-cell case study - figure 1

    Figure 1

  • The reason for the excitement around this technology is in the numbers. In lymphoma patients like Judy, over 80% of patients respond to this therapy, with over 50% of patients achieving a complete response. At an average of 6-month follow-up, about 1/3 of patients remain in remission. In B-cell acute lymphoblastic leukemia (B-ALL), the results are even more astounding, with 80-90% of patients achieving a complete response to therapy. For this reason, this was approved by the Food and Drug Administration in August for the treatment of pediatric and young adult B-ALL. This therapy does have some potentially serious and rarely fatal side effects, however, due to cytokine release syndrome and neurotoxicity. These toxicities, however, are manageable and fully reversible in most patients, and typically resolve within the first 2 weeks following CAR T-cell infusion.

    Judy was our fifth patient enrolled on this trial and, other than a few days of fever, she tolerated her CAR T-cell infusion remarkably well. Within 4 weeks, her PET scan showed that she had achieved a complete response, and by 6 weeks she was back at work in her salon (see Figure 2 below). She is now 1 year from her infusion, and her scans show an ongoing remission, she feels better than ever, and her family, friends, and clients are all thrilled to have her back!

  • CAR T-cell case study - figure 2

    Figure 2
    Before (left) and after (right)