I've only said most of this post a zillion times. Brain mets suck great big hairy green wizard balls!!! We know immunotherapy works in the brain and body. AND...we KNOW that immunotherapy combined with radiation works even better for brain mets. But...we begin again...
We'll start with a bit of relatively new information at the cellular level:
Anti-PD-1/anti-CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8+ T cell trafficking. Taggart, Andreou, Scott, et al. Proc Natl Acad Sci U S A. 2018 Jan 31.
CD103+ tumor-resident CD8+ T cells are associated with improved survival in immunotherapy naive melanoma patients and expand significantly during anti-PD1 treatment. Edwards, Wilmott, Madore, et al.Clin Cancer Res. 2018 Mar 29.
- Therapeutic blockade of immune checkpoints has revolutionized cancer treatment. Durable responses however, occur in less than half of those treated and efforts to improve treatment efficacy are confounded by a lack of understanding of the characteristics of the cells that initiate anti-tumor immune response.
- We performed multi-parameter flow cytometry and quantitative multiplex immunofluorescence staining on tumor specimens from immunotherapy-naïve melanoma patients and longitudinal biopsy specimen obtained from patients undergoing anti-PD-1 therapy.
Conclusions: Tumor-resident CD8+ T cell numbers are more prognostic than total CD8+ T cells in metastatic melanoma. In addition, they are likely to initiate response to anti-PD-1 and anti-LAG-3 treatments. We propose that the immune profile of these cells prior to treatment could inform strategies for immune checkpoint blockade.
Ok. That is good to know! Now...how to we make that happen?????
And of course...no melanoma brain met post is complete unless I'm yelling!!!! So here are a zillion posts about the benefit of immunotherapy COMBINED with radiation for brain mets:
CONCURRENT radiation and immunotherapy for brain mets is BEST!!!! (yes, AGAIN!!!)
And yes...there is this shocking finding!!! The ipi/nivo combo is better in treating melanoma in the brain than nivo alone!!! AGAIN!!! (Just like in the body....sigh....)
Between Nov 4, 2014, and April 21, 2017, 79 patients were enrolled; 36 in cohort A, 27 in cohort B, and 16 in cohort C. One patient in cohort A and two in cohort B were found to be ineligible and excluded from the study before receiving the study drug. At the data cutoff (Aug 28, 2017), with a median follow up of 17 months (IQR 8-25), intracranial responses were achieved by 16 (46%) of 35 patients in cohort A, five (20%; 7-41) of 25 in cohort B, and one (6%; 0-30) of 16 in cohort C. Intracranial complete responses occurred in six (17%) patients in cohort A, three (12%) in cohort B, and none in cohort C. Treatment-related adverse events occurred in 34 (97%) of 35 patients in cohort A, 17 (68%) of 25 in cohort B, and eight (50%) of 16 in cohort C. Grade 3 or 4 treatment-related adverse events occurred in 19 (54%) patients in cohort A, four (16%) in cohort B, and two (13%) in cohort C. No treatment-related deaths occurred.
Nivolumab combined with ipilimumab and nivolumab monotherapy are active in melanoma brain metastases. A high proportion of patients achieved an intracranial response with the combination. Thus, nivolumab combined with ipilimumab should be considered as a first-line therapy for patients with asymptomatic untreated brain metastases.Why in the world the poor folks in Cohort C had to get the shaft TWICE, I don't know!! Once in being the poor peeps who had already failed a therapy and/or had symptomatic disease and secondly by being given the less effect treatment....DAMN! Anyhow, as usual, I digress... So folks with untreated brain mets with no symptoms were put into two groups. Group A got ipi/nivo and 46% gained a response. Group B got nivo alone and attained a 20% response rate. And as noted, the folks with symptoms and/or had already failed one treatment for their brain mets were put into Group C and given nivo only, where they had only 1 response in their n=16. So...small numbers here...and to me this serves only as reinforcement for what we already know: YES!!!! Immunotherapy works in the brain!!!! (BUT....even better WITH SRS or gamma knife radiation therapy....circle back to above!!!!)
For what it's worth... - c