Thursday, September 15, 2016

Long-lasting complete responses in melanoma patients after TIL therapy

Here are a couple of previous posts on TIL:

From April:  TILs (tumor infiltrating lymphocytes) - advancing as melanoma immunotherapy and new trial 

From May: TIL - Tumor infiltrating lymphocytes (a bit of a primer)

This was published in March:

Long-lasting complete responses in patients with metastatic melanoma after adoptive cell therapy with tumor-infiltrating lymphocytes and an attenuated IL-2 regimen.  Andersen, Donia, Ellebæk, et al.  Clin Cancer Res. 2016 Mar 22.

Adoptive cell transfer therapy (ACT) based on autologous tumor infiltrating lymphocytes (TILs) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus interleukin-2 (IL-2) classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL-2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL-2 regimen.
25 patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age < 70 and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL-2 administered in an intravenous, continuous decrescendo regimen ( Identifier:NCT00937625).
Classical IL-2 related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor reactive T cells. Moreover, induction and persistence of anti-melanoma T cell responses in the peripheral blood was strongly correlated to clinical response to treatment. TIL-ACT with a reduced IL-2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable to TIL-ACT followed by HD bolus IL-2.

Basically, this study looked at doing pretty much the old-fashioned version of TIL:  Harvest cells from a tumor, grow cells, give old-time chemo to deplete the patient's existing t cells, infuse t cells that have been grown, then follow with IL-2 as usual...BUT in this case - with a decreasing dose in hopes of retaining the benefit and minimizing the suffering IL-2 can produce. Of 25 patients, there were 3 complete response and 7 partial ones.  Median overall survival was almost 22 months.  Not surprisingly, tumor regression and clinical responses were related to the greater number of t cells infused and the persistence of the anti-melanoma t cell responses in the patient's blood.

For what it's worth. - c

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