Sunday, June 14, 2015

ASCO 2015: Stage IIIA melanoma, deciding treatment by testing sentinel node?

PD-L1 expression, immune cell correlates, and PD-1 + lymphocytes in sentinel lymph node positive melanoma patients:  Implications for adjuvant PD-1 clinical trials.  Kakavand, Vilain, Wilmott, et al.  J Clin Oncol 33, 2015.

Patients with positive sentinel lymph node biopsies that undergo a completion lymphadenectomy have variable five-year survival rates ranging from 39-70%.  PD-1 and PD-L1 inhibitors have significantly improved recurrence free survival (RFS) and overall survival (OS) in stage IIIC/IV melanoma patients.  The aims of this study were to characterize populations of lymphocytes that interact with metastatic melanoma cell in sentinel lymph node biopsy, to determine tumoral PD-L1 expression and to identify whether the PD-1/PD-L1 pathway contributes to immune escape in these patients to provide a rationale for the use of anti-PD-1 inhibitors in the adjuvant setting and aid in the selection of patients for this treatment modality.

The metastatic melanoma containing sentinel nodes from 60 treatment naive patients were analyzed for CD3, CD4, CD8, FOXP3, PD-1 and PD-L1 and correlated clinico-pathologic features and outcomes.  Tumoral PD-L1 expression (greater/= to 1%) was present in 43.3% (n=26) cases.  Cox analysis showed a positive correlation between intratumoral CD3+ lymphocytes and RFS/OS, a positive correlation between intratumoral CD4+ lymphocytes and RFS/OS, and a positive correlation between intratumoral CD8+ lymphocytes and RFS/OS.  There was a negative correlation between peritumoral PD-1+ lymphocytes and RFS/OS.  

CONCLUSION:  Expression of PD-L1 in metastatic melanoma-positive sentinel node biopsy provides a rationale for trials of anti-PD1 therapy in stage IIIA melanoma patients, particularly those with peritumoral PD-1+ lymphocytes.  The expression of immune markers may also be useful to predict the outcome of patients following a positive sentinel lymph node biopsy. seems that these results indicate that if you have a sentinel node that is positive for melanoma, you should have it tested for the presence of immune cells.  (How readily available this testing is...I'm not sure.)  Then...if your tumor contains intratumoral CD3+, CD4+, CD8+ have a better chance of recurrence free survival/overall survival.  If your tumor contains PD-1+ lymphocytes you may do less well, but may respond better to anti-PD1 therapy.  It is not likely a coincidence that in this study, 43% of the tumors present were positive for that is the rough number of treatment naive patients who attain a response to anti-PD1 therapy.

By the way....none of this was remotely on the horizon much less available as a test when I had a positive sentinel node in 2003, so I have no idea what immune cells were present in my tumor. Additionally, though my melanoma tumor samples have since been tested in the course of my clinical trial, I still don't know if PD-1 or PD-L1 positive lymphocytes were present.

For what it's worth. - c

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