TIL (adoptive cell therapy, using tumor infiltrating lymphocytes) has come a long way, which is a good! In 2013, I lost a dear one, a family lost a beautiful wife and mother, students lost an incredible teacher, melanoma peeps lost a passionate advocate, and the world lost one hell of a woman when she died from melanoma and complications of TIL therapy. This post was dedicated to her that year: Ode to Pati....a fallen comrade. I beg you to view her video via the link contained within and noted here: Pati's video - What is one life worth? She had so much to say. So much yet to do. Still, she did ever so much.
This post contains the thoughts of a another incredible human - and friend - who also happens to be an amazing melanoma peep who has beaten the odds REPEATEDLY! A dedication he penned upon her death: Beautiful words, from an amazing melanoma warrior, and friend~
I don't post a great deal on TIL. But the posts I have are here - containing explanations of what is involved and a few other reports - TIL Therapy. Currently, a variety of techniques have been developed and different choices need to be made when seeking this avenue of treatment that my posts do not begin to address. Researchers are striving to make TIL more accessible and workable. Now, there is this out of ASCO this year:
Lifileucel (LN-144), a cryopreserved autologous tumor
infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma:
Evaluation of impact of prior anti-PD-1 therapy. Larkin, Sarnaik, Chesney, et al. ASCO 2021.
Background: Immune
checkpoint inhibitors (ICI) have become standard of care for treatment of
metastatic melanoma. Most patients with advanced melanoma progress on ICI and
treatment options are limited for these patients. Progression may be through
primary resistance (lack of response) or secondary resistance (initial response
then progression). Lifileucel is an adoptive cell therapy using TIL, that has
shown efficacy in patients with advanced melanoma who progress on/after an
anti-PD-1 (Sarnaik, 2020). We present the 28-month (mos) follow-up data and
highlight the impact of prior anti-PD-1 response and duration of exposure on outcome
with lifileucel.
Methods: C-144-01 is
a Phase 2, open-label, multicenter study of efficacy and safety of lifileucel
in patients with advanced melanoma who have progressed on anti-PD-1 therapy and
BRAFi ± MEKi, if BRAF V600+. We report long-term follow up on Cohort 2 (N =
66). Tumors were resected at local sites, processed in central GMP facilities
for TIL production in a 22-day manufacturing process. Therapy consisted of
nonmyeloablative lymphodepletion using 2 days of cyclophosphamide and 5 days of
fludarabine, a single infusion of lifileucel, and up to six doses of IL-2.
Objective response rate (ORR) was assessed by RECIST 1.1. Data cutoff was Dec.
14, 2020.
Results: Baseline
characteristics: 3.3 mean prior therapies (100% anti-PD-1; 80% anti-CTLA-4; 23%
BRAFi/MEKi), high baseline tumor burden (106 mm mean target lesion SOD), 42%
liver/brain lesions, 40.9% LDH greater than ULN. ORR by investigator was 36.4% (3 CR,
one new CR developed at 24 mos; 21 PR). Median duration of response (mDOR) was
not reached at median follow-up of 28 mos (DOR range: 2.2- 35.2 mos). In
responders, the median cumulative duration and median prior lines of anti-PD-1
therapy was 4.4 mos (range: 1.4-22.5 mos), and 1.5 (range: 1-4). Data in Table
demonstrates a meaningful increase in DOR to TIL with primary anti-PD-1
resistance and lower duration of time on prior anti-PD-1 therapy. No new safety
risks have been identified for lifileucel during long-term follow-up.
Conclusions: One-time
lifileucel treatment results in a 36.4% ORR, and mDOR was not reached at 28 mos
of median study follow up. One PR converted to a new CR at 24 months as
responses continue to deepen. DOR is positively associated with primary
resistance to prior anti-PD-1 therapy and with shorter cumulative prior
duration of anti-PD-1 therapy. Lifileucel may offer a better clinical outcome
when used earlier upon detection of progression on prior anti-PD-1 rather than
retreatment with anti-PD-1 based regimens. Clinical trial information:
NCT02360579.
So - these researchers have concluded that melanoma peeps who progressed on immunotherapy and BRAF/MEK inhibition (when BRAF positive) and were then treated with this particular TIL regimen - attained an overall response of 36%. Average duration of response was not reached at 28 months. Interestingly, they note that those who had a better outcome were those who had failed anti-PD-1 early on and therefore had minimal exposure to anti-PD-1. As such, they are recommending that folks who fail anti-PD-1 should pursue TIL then rather than try a re-do with anti-PD-1.
Hard decisions for sure. Thanks ratties! And thanks forever, to you dear Pati. You were and continue to be a woman who lived large and made the world a better place for all of us. - c
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