Clinical condition of melanoma peeps and associated outcomes when treated with anti-PD-1 vs anti-PD-1 and ipi

While this report is not exactly news...it is interesting and confirms prior data:

Clinical Correlates of Response to Anti-PD-1-based Therapy in Patients With Metastatic Melanoma.  Davis, Perez, Avoubi,...Sosman...et al. J Immunother. 2019 Mar 13. 

Anti-PD-1 agents, alone or in combination with ipilimumab, produce durable responses in some melanoma patients. Tumor features that correlate with response are not well defined. We collected clinical data from metastatic melanoma patients treated at 2 centers who received anti-PD-1 (n=303) or anti-PD-1+ipilimumab (n=57). We correlated number of metastases, diameter of largest tumor (tumor bulk), and organ involvement with response rate (RR), progression-free survival (PFS), and overall survival (OS). Patients with diameter of largest tumor less than or equal to 2 cm had a 53% RR, whereas those with largest tumor greater than 2 cm had a 38% RR. Those with liver metastases had lower RR (25% vs. 43%). RR to anti-PD-1 was greater in patients with less than or equal to 10 metastases compared with those with greater than 10 (39% vs. 27%). In multivariable analyses, size of the largest tumor was independently associated with PFS, OS, and RR, whereas AJCC stage, lactate dehydrogenase, liver metastases, ECOG performance status, number of metastases, and prior therapies were not. In patients treated with anti-PD-1+ipilimumab, however, tumor bulk was not associated with outcomes, although number of metastases was associated with PFS  and RR but not OS. Pathologic analysis did not reveal differences in T-cell infiltration in bulky versus small tumors. Tumor bulk, defined by diameter of largest tumor, was strongly and independently associated with clinical outcomes in anti-PD-1 but not in anti-PD-1+ipilimumab. In conjunction with molecular biomarkers, clinical predictors may help guide selection of immunotherapy agents.

So....this study looked at 360 metastatic melanoma peeps.  303 were given anti-PD-1 alone and 57 were treated with the anti-PD-1 plus ipi.  The researchers looked at response rate (RR), progression-free survival (PFS) and overall survival in the groups to see if there were any clinical consistencies between those results.  They found that (not surprisingly) patients whose largest tumor was less than or equal to 2 cm had a 53% RR while those whose largest tumor measured more than 2 cm had a 38% response rate.  Patients with less than 10 mets had a better RR than those who had more than 10 (39% vs 27%).  Folks with liver mets did less well, with RR of 25% vs 43%.  In a separate, overarching analysis, size of the largest tumor was independently associated with all parameters (PFS, OS, and RR) - while LDH, liver mets, # of mets, and prior therapies were not.  HOWEVER, with the ipi/anti-PD-1 combo, tumor size was NOT associated with out comes, though the NUMBER of mets was still associated with PFS and RR, but not OS.  Analysis of tumor pathology did not reveal any differences in T-cell action in bulky vs small tumors.

We have long known that immunotherapy works best with the lowest tumor burden.  Lots of research indicates that LDH is not a very reliable marker.  We know that liver mets are difficult to treat (early research link here).  We also know that there are no crystal clear parameters (YET!!!) that tell us who will do well on anti-PD-1 as a single agent vs those who need to be treated with anti-PD-1 combined with ipi.  AND ~ that is a hard decision, given the desire to rid ourselves of melanoma versus the unfortunate side effects the combo can trigger that are more easily avoided with anti-PD-1 alone.  BUT ~ given what we have long known and the information presented here....if I had lots of mets, large mets or liver involvement...I would be opting for the combo.  Just saying.  For what it's worth. - c