Ipi and radiation...a good combo for melanoma mets...brain and otherwise!!!

We've been hearing more and more about this!  Here are two new articles...

Ipilimumab and radiation therapy for melanoma brain metastasis. 
Silk, Bassetti, West, Tsien, Lao.  Cancer Med. 2013 December.

Ipilimumab, an antibody that enhances T-cell activation, may augment immunogenicity of tumor cells that are injured by radiation therapy.  We hypothesized that patients with melanoma brain metastasis treated with both ipi and radiotherapy would have improved overall survival, and that the sequence of treatments may affect disease control in the brain.  We analyzed the clinical and radiographic records of melanoma patients with brain mets who were treated with whole brain radiation therapy or stereotactic radiosurgery between 2005 and 2012. ...Several patients were identified, 33 of whom received ipi and 37 who did not.  The patients who received ipi had a...median survival of 18.3 months, compared with 5.3 months for patients who did not received ipi.  Ipi and stereotactic radiosurgery were each significant predictors of improved overall survival.  Four of 10 evaluable patients (40%) who received ipi prior to radiotherapy demonstrated a partial response to radiotherapy, compared with two of 22 evaluable patients (9.1%) who did not received ipi.  Ipi is associated with a significantly reduced risk of death in patients with melanoma brain mets who underwent radiotherapy, and this finding supports the need for mulimodality therapy to optimize patient outcomes.

So...40% of patients with melanoma brain mets who had ipi then radiation showed a partial response.  While only 9% of patients treated only with radiotherapy (no ipi) showed the same response.  The numbers of patients in this review are small and wonky...but this effect is showing up more and more as talking points when the melanoma big dogs are interviewed and in the literature.

Combined ipi and radiotherapy for metastatic melanoma.
Menzel, Abendroth, Kashani-Sabet, Minor. Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco. International Journal of Radiation Oncology.  October 2013.

The efficacy and toxicity of ipi when combined with radiotherapy (RT) is unclear, though an abscopal effect has recently been reported in multiple patients receiving ipi and subsequent RT. This is our retrospective experience...
Methods:  Melanoma patients treated with ipi and subsequent RT...NON-cranial lesions were identified.  All patients had CT scans within 1 and 3 months of RT initiation and conclusion respectively....
Results:  Ten patients with median age of 65 years received RT via a linear accelerator of CyberKnife...Median number of lesions irradiated lesions was 1 (range = 1-3).  Patients received ipi (3mg/kg, 3-4 doses every 6 months) for a median of 11.9 months pre-RT.  Eight patients had progressive disease, two had stable disease at RT initiation.  At a median follow-up of 12+ months, median progression free survival and overall survival have not been reached.  At last follow-up, 2 patients had complete responses, 4 had partial responses, 1 had stable disease, and 3 had progressive disease.  All irradiated lesions were controlled.  There was one death related to brain mets.  Among 5 patients evaluated for abscopal effect, 2 had progressive disease out of field, 1 had stable disease out of field, and 2 evidenced abscopal effect, with regression or clearance of non-irradiated lesions.
CONCLUSIONS:  Combined ipi and RT is a treatment option in metastatic melanoma with apparently little additive toxicity when hypofractionated RT is employed.  The abscopal effect is an increasingly common phenomenon in observed patients treated with this regimen.

So....Still small numbers...and still sucky results for many...but better than ipi or radiation alone for others!!!  After getting ipi....8 patients had progressive disease and 2 had stable disease.  BUT...after getting RT, 12+ months out - 2 have had a complete response, 4 have had partial responses, 1 has stable disease, and 3 have progressive disease with one death.  Still better than the 8 with progressive disease after ipi alone!!!  Per my Bentie statistician that is a clinical benefit of 70%!!!!  Then there is the abscopal effect to consider, with, of the 5 patients evaluated for it, 2 demonstrating progressive disease out of the field of radiation, 1 with stable tumors out of the field, and 2 with a positive abscopal effect with tumors regressed or cleared in non-radiated areas!  I think we are still unclear if ipi followed by RT is best...or vice versa...or if it matters at all.  I know there are more studies looking at this ongoing.

Fingers crossed for all of you out there!!! - c