Baseline levels of IL-9 predicted response to Adoptive cell therapy (ACT) using TIL in melanoma and a complete response in TIL paired with nivo (a case study)

A little old, and I don't tend to post much on TIL - but still....  Here are two reports:

Prospective analysis of adoptive TIL therapy in patients with metastatic melanoma: response, impact of anti-CTLA4, and biomarkers to predict clinical outcome. Forget, Haymaker, Hess, et al. Clin Cancer Res. 2018 May 30.

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has consistently demonstrated clinical efficacy in metastatic melanoma. Recent widespread use of checkpoint blockade has shifted the treatment landscape, raising questions regarding impact of these therapies on response to TIL and appropriate immunotherapy sequence.

Seventy-four metastatic melanoma patients were treated with autologous TIL and evaluated for clinical response according to irRC, overall survival and progression free survival. Immunologic factors associated with response were also evaluated.

Best overall response for the entire cohort was 42%; 47% in 43 checkpoint naïve patients, 38% when patients were exposed to anti-CTLA4 alone (21 patients) and 33% if also exposed to anti-PD1 (9 patients) prior to TIL ACT. Median overall survival was 17.3 months; 24.6 months in CTLA4 naïve patients and 8.6 months in patients with prior CTLA4 blockade. The latter patients were infused with fewer TIL and experienced a shorter duration of response. Infusion of higher numbers of TIL with CD8 predominance and expression of BTLA correlated with improved response in anti-CTLA-4 naive patients, but not in anti-CTLA-4 refractory patients. Baseline serum levels of IL-9 predicted response to TIL ACT, while TIL persistence, tumor recognition and mutation burden did not correlate with outcome.

This study demonstrates the deleterious effects of prior exposure to anti-CTLA-4 (though perhaps that result is only due to those patients being "infused with fewer TIL"??????!!!) on TIL ACT durability and perhaps more importantly shows that baseline IL-9 levels can potentially serve as a predictive tool for response and help guide treatment sequence and selection.

On the other hand:

Rapid complete remission of metastatic melanoma after first-line treatment with nivolumab plus tumor-infiltrating lymphocytes. Zhao, Yang, Li, et al. Immunotherapy. 2018 Sep 10.

Melanoma is the most common type of skin cancer in both men and women in the USA. The standard treatment modality for advanced melanoma is immunotherapy, either alone or in combination. As single-agent immunotherapy is usually inadequate, combined immunotherapy might be a good choice and combined treatment modalities appropriate for melanoma need to be explored. Herein, we report a case of metastatic melanoma successfully treated with combined therapy of tumor-infiltrating lymphocytes and nivolumab. Complete remission was achieved approximately 4 months after the initiation of treatment. The treatment was well tolerated and only grade 1 fatigue occurred. The patient was still on complete remission 1 year after stopping the treatment. Our result showed that this treatment modality might be an ideal option for patients with metastatic melanoma.

Wonder if that patient would have had that complete and durable response to nivo alone, as I know from personal experience (and that of others) that nivo alone CAN provide complete responses in contradiction to the statements made in this report.  Additionally, how did this patient attain this therapy?  Hmmm....

For what it's worth. - c