Sunday, October 11, 2015

Why immunotherapy is good for lots of folks...not just those with melanoma and how radiotherapy may make it even better!

Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy.  Lancet Oncol. 2015 Oct;16(13):e498-e509.  Sharabi, Lim, DeWeese, Drake.

"Checkpoint blockade immunotherapy has received mainstream attention as a result of striking and durable clinical responses in some patients with metastatic disease and a reasonable response rate in many tumor types. The activity of checkpoint blockade immunotherapy is not restricted to melanoma or lung cancer, and additional indications are expected in the future, with responses already reported in renal cancer, bladder cancer, and Hodgkin's lymphoma among many others. Additionally, the interactions between radiation and the immune system have been investigated, with several studies describing the synergistic effects on local and distant tumor control when radiation therapy is combined with immunotherapy. Clinical enthusiasm for this approach is strengthened by the many ongoing trials combining immunotherapy with definitive and palliative radiation."  

The article goes on to discuss the mechanisms of immunotherapy (Something that has been beaten to death on this blog!!!) as well as the reasons for potential synergy between radiation and immunotherapy, as well as a reintroduction of..."the notion of radiosensitising immunotherapy, akin to radiosensitising chemotherapy, as a potential definitive therapeutic modality."

Clearly, this is a plan I like.  Help more folks.  Make what is good even better!!!  More links to articles noting the synergy between radiation and immunotherapy:  

Way to go, ratties!  Way to go! - c


  1. Hi Celeste - thank you for keeping up with your blog over the years. I have been checking in, off and on for the last three + years, since I got diagnosed with Stage IV melanoma.

    I am also the beneficiary of immunotherapy and radiation (stereotactic)...have had mets in lungs, liver, stomach as well as 98 brain tumors treated with Gamma Knife @ the University of Colorado. Still topside.

    Just started a blog called "" to try to offer whatever hope and experience I might have If there is anyone 'out here' on the internet needing to hear my story.
    Leland Fay

  2. My goodness! Topside is no small feat!!! Good for you. I wish you well! - c

  3. Here is some clinical data recently published by Dana Farber folks ( Hodi et al) on radiation / Immunotherapy synergy:

    Have you seen any reports / data around synergy of radiation + Pd-1 agents ?

    1. Funny you mention that article. It is sitting on my computer for posting today! But, other than the links in the above post...and the results of the folks in my study who were treated with SRS as well as Nivo and are doing well...I do not have specific outcomes as yet for radiotherapy combined with anti-PD1 specifically. But....if radiotherapy has synergistic action with any would be reasonable to expect combined radiation and anti-PD1 would provide that as well. Thanks for sharing. c

  4. Thanks Celeste ;

    In your study, what % of pts who had Nivo + radiation had clinical benefit vs those who progressed? Would be great to know .

    One more study had results published today at ASTRO ( RadOnc annual meeting) . Posting the abstract below:

    A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

    04:45 PM - 06:15 PM
    Presentation Number
    S. M. Hiniker, S. A. Reddy, H. T. Maecker, S. M. Swetter, L. Shura, and S. J. Knox; Stanford University, Stanford, CA
    Purpose/Objective(s): Local radiation therapy (RT) in combination with systemic anti-CTLA-4 immunotherapy has the potential to enhance the induction of systemic antimelanoma immune responses. The primary objective of this trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. Secondary objectives included assessment of induction of antimelanoma immune responses using laboratory correlative studies.
    Materials/Methods: In our prospective, Phase 2 clinical trial, 20 (14 men, 6 women, ages 18-83 years) evaluable patients with stage IV melanoma were treated with palliative RT and ipilimumab (3mg/kg) every 3 weeks for a total of 4 cycles. Palliative RT to 1-2 sites of disease was initiated within 5 days of the first dose of ipilimumab. Patients were required to have at least one nonirradiated metastasis measuring at least 1.5cm for assessment of response to therapy. Tumor imaging studies were obtained at baseline prior to treatment, 2-4 weeks following the fourth dose of ipilimumab, and every 3 months until disease progression. Both Response Evaluation Criteria in Solid Tumors (RECIST) and Immune Response Criteria (IRC) were used to assess tumor responses. Patients were monitored for safety, and laboratory immune response parameters were measured before and during the treatment period, including enumeration of major cell subsets, as well as myeloid-derived suppressor cells (MDSC), and antigen-specific T cell responses by intracellular cytokine staining.

    Results: Of the 20 evaluable patients treated to date, 11 patients (55.0%) had an initial response to therapy, including complete and partial responses (CR, PR) as well as stable disease (SD) at median follow-up of 38 weeks. Of the responders, one patient (9.1%) had achieved an ongoing systemic CR to the combination therapy. Five patients (45.4%) have an ongoing PR and 5 additional patients (45.4%) initially had SD following treatment without progression for a median of 39 weeks (range 26-76 weeks). Nine patients had progressive disease by IRC on the first posttreatment scan. Combined treatment has been well tolerated with no unexpected toxicities, and no apparent exacerbation of either radiation or ipilimumab-associated toxicities. Analysis of the immune response data suggests that pro-inflammatory cytokines are elevated in responders (eg, MCP-1, MIG and IP-10), and that there may be a relationship between elevated CD8 activated T cells and response.

    Conclusion: This is one of the first prospective clinical trials to report results from the treatment of metastatic melanoma with the combination of RT and systemic immunotherapy. Our results demonstrate that a subset of patients can achieve significant clinical benefit from this combination therapy, and that this in situ tumor vaccine strategy is a promising area for continued clinical investigation.

  5. Andy,

    You can use the search bubble on the top left of my blog to search any topic you like. Here is the report on my study:

    And here is my 'report' on the report:

    You are not likely to find the data you seek in either of these reports. Anti-PD1 and the admission that radiotherapy is synergistic with immunotherapy are both newly accepted facets of melanoma treatment. I have lived through both being doubted. Nevertheless, my ratties have demonstrated continued existence....esp those of us post SRS to brain mets. So...that says a lot to me!!! I am a little puzzled that your report is dated 10/20/2015. That is futuristic indeed!!! However, now that the melanoma big dogs have accepted that both abscopal responses and increased overall responses occur when immunotherapy is combined with radiation...many studies are ongoing....and a good thing. You might also like the post I put out today. Thanks again!

  6. Thanks much Celesete. Your posts are most insightful and helpful.

    The abstract that I posted above will be presented on 10/20 at the Annual ASTRO comference; but released today at the start of the conference.

    There are some more that will be presented on immunotherapy / radiation synergy

    1. Cool. Perhaps more data will be presented at the conference that will speak more directly to the combination of radiation and anti-PD1. Thanks again!