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Chemotherapy Pretreatment May Boost Effectiveness of CAR T-Cell Therapy in Patients With Lymphoma and Leukemia

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Key Points

  • A study of 11 patients with lymphoma or leukemia investigating third-generation CD19 CAR T-cell therapy combined with chemotherapy pretreatment has resulted in complete remissions or complete clinical responses in 6 patients.
  • Of the patients who had a complete response, five had received preconditioning therapy, which included cyclophosphamide and fludarabine to decrease immunosuppressive cells.
  • Providing both tumor-reductive chemotherapy prior to CAR T-cell infusion and preconditioning chemotherapy before CAR T-cell infusion may improve outcomes for patients with leukemia and lymphoma. 

A small phase I/IIa study of third-generation CD19 CAR (chimeric-antigen receptor) T-cell therapy combined with chemotherapy pretreatment has resulted in complete responses in 6 of the 11 patients with relapsed or refractory lymphoma and leukemia enrolled in the study. Although CAR T-cell therapy has shown promising results in patients with leukemia, treating lymphoma with the therapy has been challenging because of the higher concentration of immunosuppressive cells, which can inhibit the effectiveness of CAR T cells. Other barriers, including defective blood vessels and fibrotic tissue, may also make it difficult for CAR T cells to penetrate the tumor.

The study, abstract A041, by Enblad et al is being presented at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, September 16–19 in New York. The conference is being cosponsored by the American Association for Cancer Research, the Cancer Research Institute, the Association for Cancer Immunotherapy, and the European Academy of Tumor Immunology.

Study Methodology

The study was a collaborative effort between Uppsala University in Sweden and Baylor College of Medicine in Houston, Texas. The researchers enrolled 11 patients with relapsed or refractory CD19 B-cell malignancy into the study. The patients had no other curative treatment options available. Among the 11 patients, 4 had leukemia (acute lymphoblastic leukemia or chronic lymphocytic leukemia) and 7 had lymphoma (diffuse large B-cell lymphoma or Burkitt lymphoma).

Autologous CAR T cells were manufactured using a gamma retrovirus encoding the CAR and expanded by aCD3/aCD28/IL2. During CAR T-cell production, all lymphoma patients received treatment to control their tumor burden (–90 to –3 days before T-cell infusion). The type of treatment depended on the type of lymphoma and previous treatments. In addition, prior to T-cell infusion (day –2 to –1), six patients, three with leukemia and three with lymphoma, received cyclophosphamide (500 mg/m2) and fludarabine (25 mg/m2) as preconditioning to decrease immunosuppressive cells. All patients received one infusion of CAR T cells as outpatients. Patients received one of the three doses tested.

Study Findings

Six patients, three with leukemia and three with lymphoma, had complete remissions or complete clinical responses; however, two relapsed later. Of the patients who had complete responses, five had received preconditioning therapy. Cytokine release syndrome, a common side effect of CAR T-cell therapy, was treated at the hospital, and most patients had a rapid relief of their symptoms. Four patients did not respond to treatment and progressed early; and one patient is still too early to evaluate.

“Of the 11 patients recruited to this trial, six had complete responses,” said Angelica Loskog, PhD, Professor of Immunotherapy at Uppsala University and a coauthor of the study, in a statement. “The complete responses in lymphoma patients despite the fact that they received only low doses of preconditioning compared with other published data surprised us. The strategy of both providing tumor-reductive chemotherapy for weeks prior to CAR T-cell infusion combined with preconditioning just before CAR T-cell infusion seems to offer promise.”

The study was funded by AFA Insurance AB and the Swedish Cancer Society.

Dr. Loskog is Chief Executive Officer and Board Member of Lokon Pharma AB; Chairwoman of the Board of Vivolux AB and Repos Pharma AB; and scientific advisor to Nexttobe AB. She holds royalty agreements with Lokon Pharma AB and Alligator Bioscience AB. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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