Friday, October 21, 2016

One more time....better responses when radiation is combined with immunotherapy

While we've learned that radiation alone doesn't help that much in melanoma patients:

Radiation alone, not such a good idea in melanoma!!!

Radiation of lymph node basin: not so helpful if that is all that is done...

We have also learned that radiation COMBINED with immunotherapy can make a real difference!!!

Brain mets in Melanoma - don't wait to add immunotherapy after SRS!

Nivo (Opdivo) with radiation = better for melanoma patients with brain mets

And finally....this link....that contains several more links within:  Review of abscopal responses after radiotherapy in melanoma patients

Now there is this:

A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma.  Hiniker, Reddy, Maecker, et al.  Int J Radiat Oncol Biol Phys. 2016 Nov 16.  

Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte-associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses.  In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had greater or equal to1 nonirradiated metastasis measuring greater or equal to 1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment.  Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response.  This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the potential to be even more effective in combination with RT.

We still have folks being told by oncologists that they can't combine SRS and immunotherapy or can't have one after the other "too soon" due to some sort of bad effect.  Now, while there may be a few exceptions where that reasoning may apply, it is not where the data is leading us!!!  Think Jimmy Carter.  Cut out the liver met, zap the brain tumor, start, zap, boom.  He's already off meds and latest report says melanoma free!!!

Hang tough ratties!  Take reports to your docs as needed!!! Wishing you well. - c


  1. I still can't figure out why I'm not getting Anti PD-1
    Reasoning being no metastatic disease

    Thanks for the info

  2. I certainly understand your frustration. Unfortunately, in Dec of 2014 nivo/Opdivo was only FDA approved for those with Stage IV metastatic or unresectable melanoma(though its use could only be after failing ipi or BRAFi if you were BRAF positive). In October 2015...ipi/nivo was approved for use in metastatic melanoma patients if BRAF V600 (which makes absolutely no difference, but that was the data group upon which the approval was made). In Jan of this year, ipi/nivo was approved for all melanoma Stage IV/III patients with metastatic or non-resectable disease. In Dec 2015 Pembro/Keytruda was approved for the same folks...Stage III/IV with active or unresectable lesions. Clearly, this leaves Stage III AND Stage IV patients who at the moment are NED out in the cold. Only ipi and interferon are approved as adjuvant meds....despite plenty of evidence that anti-PD1 is also effective in that setting!! What is doubly that there are those who DO manage to get treated with nivo or pembro even though they too, do NOT have active disease. While I think that is is not fair that there are those who deserve and wish to partake of that treatment who are not given the opportunity. I keep hoping that it will change soon. But, not soon enough. I am a believer that the squeaky wheel will get the oil, but that is not an easy position to take and is not always least not in the time frame within which it needs to occur. Asking, however, never hurts. Bringing forth documentation as to the data that proves its worth and the fact that others DID attain anti-PD1 as adjuvant may be helpful. I am sorry for you and others who are in need of adjuvant care, but find themselves in Melanoma Neverland. Hang in there.

  3. On the flip side...the article posted here shows clear benefit of ipi when combined with radiation. And my recent post:

    ...shows the benefit of ipi as adjuvant for Stage III patients. I would have given anything to have been able to take ipi when I was Stage IV, post brain and lung mets...but rendered NED. However, it was not FDA approved for anybody at that time. Hang tough. Melanoma world is a crazy place.

  4. I had 98 lesions in brain treated after starting ippi 4 years ago. Still here. Lesions remain in brain and throughout body but not progression. I just had a lymph node by liver treated with cyber knife because it was bigger on last scan. This could be due to t-cell infiltration (one study said that was indicated by 39% of biopsies performed) or progressive disease. Also on @ my 35th infusion of anti-pd1 (keytruda)...Either way I am hoping for abscopal effect.

    1. Rooting for you AND the abscopal response!