Data from the first really large trial of CAR-T in treatment of lymphoma

As yet, there has been no serious clinical exploration of whether the new types of CAR-T treatment can be applied to patients with either prostate cancer or any other form of solid tumor.

CAR-T treatment is based on the collection of T cells (a type of immune cell collected from the blood of cancer patients) and the genetic transformation of those T cells to produce special receptors on their cell surfaces called chimeric antigen receptors (CARs).

Over the past 5 years of so, based on some of the very early work by Dr. Carl June and other researchers at the University of Pennsylvania, this technique has been used to treat a range of patients with severe forms of blood cancer like leukemia and lymphoma in early stage trials (with some hiccups along the way).

We now have the very first data from a large trial (the ZUMA-1 trial) that will be submitted to the US Food and Drug Administration for approval of a form of CAR-T treatment developed by Kite Pharmaceuticals and known as axicabtagene ciloleucel (formerly KTE-C19).

According to a media release issued early today by the company, their investigational drug has shown the following effects in the treatment of patients with a form of blood cancer known as chemo-refractory, aggressive B-cell non-Hodgkin lymphoma (NHL):

  • At 6 months of follow-up post-treatment,
    • 41/101 patients (41 percent) exhibited a response to treatment.
    • 36/101 patients (36 percent) exhibited a complete response to treatment.
    • 5/101 patients (5 percent) have exhibited highly significant and durable partial responses to treatment with minimal abnormalities in PET scans.
  • At 9 months of follow-up, one of the above-mentioned partial responses converted to a complete response.
  • At an average (median) follow-up of 8.7 months, the average (median) overall survival (OS) has not yet been reached.
  • Grade 3 and grade 4 adverse effects to treatment are relatively common and include
    • Anemia (43 percent)
    • Neutropenia (39 percent)
    • Decreased neutrophil count (32 percent)
    • Febrile neutropenia (31 percent)
    • Decreased white blood cell count (29 percent)
    • Thrombocytopenia (24 percent)
    • Encephalopathy (21 percent)
    • Decreased lymphocyte count (20 percent)
  • As compared to data from the earlier, interim analysis
    • Grade 3 or higher cytokine release syndrome (CRS) decreased from 18 to 13 percent.
    • Grade 3 or higher neurologic events decreased from 34 to 28 percent.

The company’s media release also notes that data from the SCHOLAR-1 study presented at the annual meeting of ASCO in 2016 showed that median overall survival in a similar patient population was 6.6 months, so the data from the ZUMA-1 trial (which was not a randomized, double-blind Phase III trial, but rather a Phase I/II trial in which all patients were treated with the active drug) does appear to be indicating a significant increase in overall survival as compared to the current standard care among this group of patients with chemo-refractory NHL. However, it also has to be noted that the risk for significant (albeit manageable) adverse reactions to this type of therapy is considerable.

Even through we have no idea, as yet, whether this type of treatment can be effectively applied in the treatment of prostate cancer, the fact that this type of treatment does appear to be effective in the management of aggressive, advanced forms of some cancers suggests it may have considerable potential moving forward — especially if it is shown to be effective in earlier stages of aggressive forms of cancer when the patients are generally healthier and therefore better able to handle the risk for adverse effects of treatment.

We will note, however, that we expect the cost of such therapy (if approved by the US Food & Drug Administration and/or the European Medicines Agency) to be extremely high.

2 Responses

  1. This sounds comparable in its procedure to Provenge that gathers dendritic rather than T-cells. Are the T-cells collected via aphoresis?

  2. Rick:

    This is a very different process. Individual T cells do not have to be collected from individual patients, and the product used in treatment using Kite Pharmaceuticals’ methodology is biochemically engineered and can be used in any appropriate patient.

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