Monday, 31 October 2016

Gamma Delta

Hi Stephen,

Do you have any information about Gamma Delta therapy in GBM? It was recently brought up but am not sure if it was tried before in GBM- can't find anything that says it was. Also, what would be potential side effects? Could it lead to swelling and edema as those seen with PD-1 inhibitors and CTL4 antibodies?



  1. There has been several laboratory studies of gamma delta T-cell therapy for GBM, but I haven't seen any actual clinical studies.

  2. My husband done this therapy in Country Georgia, Tbilisi in Mardaleishvili clinic ( with help of Doctor Gocha Shatarishvili ( Side effect can be swelling, as we were told, but my husband didn’t had it. He has done it in 11th of August and on the next MRI on 10th of October, there was no growing shown. He was diagnosed on 3th of May, dome 40 days of radiation an Temodal till end of June.

  3. Noha,
    Thanks for this post. I was interested in your comment about brain swelling/edema with PD-1 agents. I haven't been able to find any reference in the literature to this side effect. My wife has been on a research protocol with nivolumab/Opdivo, and has had *severe* edema of the brain (interestingly, only on the side of the GBM tumor, which was (grossly) completely removed at surgery. Perhaps the reaction was to glioma cells that weren't showing up on MRI.

    In our case, the logical thing would be to give a much lower dose than 3mg/kg q 2 weeks -- but that's not in the protocol, so she'll probably have to exit the study.

    I'm interested in what you've learned about edema with PD-1 agents.

    1. Although there has been discussion of checkpoint inhibitor antibodies causing such side-effects, I too have trouble finding any reports in the literature.

      In the phase 1 trial of nivolumab alone and nivolumab + ipilimumab for recurrent GBM, severe treatment-related adverse events occurred in 7 out of 10 patients doing the combination therapy, but the serious adverse events reported were: colitis (2), diarrhea (2), hypothyroidism (2), hyperthyroidism (1), ALT increased (2), AST increased (1), lipase incrased (1), decreased appetite (1), diabetic ketoacidosis (1), hyperglycemia (1), hypocalcemia (1), hypomagnesemia (1), cholecystitis (1), sepsis (1), confusional state (1), acute renal failure (1), and pancreatitis (1).

      In the group taking nivolumab alone (n=10), only 2 out of 10 patients had severe adverse events: hypothyroidism (1), pneumonitis (1), and chest pain (1).

      This data came from a 2015 ASCO poster that I'll upload to the library.

      In a phase 2 trial of ipilimumab (Yervoy) for 72 melanoma patients with brain metastases:

      note is that CNS events were infrequent
      and attributable to the tumor, with no
      clearly drug- or immune-related adverse
      effects occurring in the CNS."

      "Despite early concern that
      ipilimumab-related inflammation and/or
      edema in brain lesions would increase morbidity,
      this did not appear to be the case."

      However, I'm sure there's a fair amount of unpublished toxicity data from the numerous checkpoint inhibitor trials for GBM, and one might have to talk to the clinicians leading these trials for more detailed info on this question.

  4. Steve and Stephen, sorry for the late reply. My husband has not been well and u have not been able to log in as frequently. Here is our experience in case it would be of help:
    - my husband was in Merck's PD-1 inhibitor ( keytruda) between Jan 2015 and June 2015. He was on the highest dose of 10mg/kg every 2 weeks. At the time, there was no clinical trial that would guarantee he gets a PD-1 inhibitor . There was only one that randomized between avastin or Opdivo blindly and we didn't want to get avastin at the time. Hence, we went with the keytruda study grouping solid tumors together at the highest dose. He never had a swelling. What happened was 2 month after enrolling, he started having subtle enhancements that the NO was not sure whether they are inflammation or recurrence. Things stayed this way with increased enhancements till in June we decided this can't be enhancement and he sat for a craniotomy that confirmed our doubts that this was definetly recurrence with minimal swelling or inflammation. The pathology was confirmed by Both Dana Farber and Johns Hopkins.
    - my husband starts taking Opdivo with avastin .. Was not enough to curb the growth.. Again, Opdivo never resulted in swelling.. Was not effective for him in curbing tumor growth even when combined with avastin and re radiation but he never experienced swelling from it.
    - we added ipilimumab in June. He only had 1 dose and that was the worst decision we made on his treatment regimen. He has been suffering from auto immune response in the liver that got him hospitalized for over a month and led to him taking immunosuppressive medications that basically let the tumor take over and change into a multifocal disease with 3 tumors in 3 different lobes. He is deteriorating and even though he never took ipilimumab again, the liver never really recovered fully which is preventing him from continuing treatment and is giving the tumors the chance to grow.

    The above is just our experience.. Might not mean that others won't have a different experience as you all know. Hope it is of help and Steve, I wish you and your wife the best and may you find light to make the best treatment decisions for her.


  5. Hi Natalia, thanks for sharing your husband's experience. Can I ask u: when your husband did the gamma delta therapy, was he on any other treatments along with it? Did he get bothe the IL-2 and Zometa?