📬 Melanoma Intelligence Digest — Week 2026-W28
Real-world TAMARIS data show an OS benefit for adjuvant therapy in stage III melanoma except stage IIIA, checkpoint inhibitors after TIL progression show limited activity, and BCL2/MCL1 targeting overcomes BRAF/MEK inhibitor resistance preclinically.
⚡ TL;DR
📄 Publications
- Immune checkpoint inhibitor therapy after tumor-infiltrating lymphocytes in unresectable melanoma. — Among 133 patients assessed for response to ICI after TIL progression, ORR was 11% (n=14), including 3 complete responses and 11 partial responses
- Personalized targeting of BCL2 family proteins overcomes acquired resistance to BRAF-MEK inhibitors in preclinical melanoma. — Combining BCL2 inhibitors (navitoclax or venetoclax) with BRAFi+MEKi induces tumor regressions in a subset of resistant PDX models
🐦 Twitter / 🦋 Bluesky
- BCL2 family targeting overcomes acquired BRAF/MEK inhibitor resistance in preclinical melanoma — Adding BCL2 inhibitors (navitoclax/venetoclax) restored tumor regressions in a subset of BRAFm melanoma PDX models
- Update: Checkpoint inhibition after TIL progression shows limited activity across 14 international centers — Post-TIL ICI activity was limited, with ORR 11% and median OS 8.8 months
Full details below ↓
📄 What's Being Published
Immune checkpoint inhibitor therapy after tumor-infiltrating lymphocytes in unresectable melanoma. — Smithy James William et al., J Immunother Cancer
Among 133 patients assessed for response to ICI after TIL progression, the ORR was 11% (n=14; 95% CI 5.9% to 17%), including 3 complete responses (2.3%) and 11 partial responses (8.3%). At a median follow-up among survivors of 21 months, median OS from post-TIL ICI was 8.8 months (95% CI 6.5 to 12 months). In the safety cohort (n=138), therapy-related toxicity occurred in 31 patients (22%), among whom 7 patients (5.1%) experienced recurrence of an adverse event experienced with prior ICI treatment.
Clinical bottom line: Checkpoint inhibition after TIL progression yields an ORR of only 11% and median OS of 8.8 months without synergistic toxicity, and this week the study authors amplified the finding across multiple international centers as a call for novel trials in this setting.
Survival outcomes of adjuvant therapy in resected stage III melanoma: Results from a real-life cohort study (TAMARIS). — Erard Théo et al., Eur J Cancer
Among 1016 patients (median age: 60 years), 701 (69%) received adjuvant therapies with either anti-PD-1 (n=588) or BRAFi/MEKi (n=113). OS was significantly higher in the adjuvant group compared to the control group (HR: 0.62, 95% CI 0.47–0.80, P=0.003), confirmed in multivariate analysis and after IPTW-adjustment (HR: 0.68, 95% CI 0.49–0.94, P=0.020). In subgroup analyses, adjuvant treatment had a significant positive impact on OS across most subgroups, but not for stage IIIA.
Clinical bottom line: Real-world TAMARIS data indicate a significant overall survival benefit of adjuvant therapy in AJCC 8th edition stage III melanoma, but not in stage IIIA disease.
Personalized targeting of BCL2 family proteins overcomes acquired resistance to BRAF-MEK inhibitors in preclinical melanoma. — Y N Vashisht Gopal et al., Nat Commun
In vivo testing of a large collection of patient-derived xenograft (PDX) models from melanoma patients with acquired resistance to BRAFi or BRAFi+MEKi shows that combining BCL2 inhibitors (navitoclax or venetoclax) with BRAFi+MEKi induces tumor regressions in a subset of these PDXs. High basal BCL2 predicts response whereas high basal MCL1 predicts resistance to this strategy. Combining BRAFi+MEKi with an MCL1 inhibitor counteracts resistance and decreases MCL1i-associated markers of cardiotoxicity.
Clinical bottom line: Personalized targeting of BCL2 family proteins, guided by basal BCL2 and MCL1 expression, restores tumor regression in preclinical BRAF/MEK inhibitor-resistant melanoma models.
🗣️ What People Were Discussing This Week
How these are chosen: filtered for clinical relevance, grouped by the new development discussed, then ordered by engagement (bookmarks and reposts).
BCL2 family targeting overcomes acquired BRAF/MEK inhibitor resistance in preclinical melanoma
Adding BCL2 inhibitors (navitoclax/venetoclax) restored tumor regressions in a subset of BRAFm melanoma PDX models. High BCL2 expression predicted response, while MCL1 identified resistant tumors. Specialists debated whether baseline BCL2 and MCL1 expression can stratify which BRAF/MEK inhibitor-resistant patients might benefit from adding a BCL2-family inhibitor.
Discussed by: @OncoAlert, @MarioBalsaMD
Update: Checkpoint inhibition after TIL progression shows limited activity across 14 international centers
Post-TIL ICI activity was limited, with ORR 11% and median OS 8.8 months, prompting clinicians to examine what outcomes checkpoint inhibitors offer after progression on TIL therapy in melanoma. The central debate concerns whether retreatment with a previously unreceived checkpoint inhibitor offers meaningful benefit when patients progress after TIL therapy.
Discussed by: @ja_ocejo, @DoniaMarco
🔥 Top Ranked Tweets
Allison Betof, MD, PhD, FASCO @DrBetofMDPhD
RT @jitcancer: New #JITC short report: "Immune checkpoint inhibitor therapy after tumor-infiltrating lymphocytes in unresectable melanoma" https://t.co/6bZ7SPPNsw
@DrBetofMDPhD @ShirlyGrynberg @ajsfurness @ja_ocejo @bbuchbinderMD @LutzkyJose
@evanlipson @DoniaMarco @HaanenJohn https://t.co/LVJ5MrT94D
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Antonio Ocejo @ja_ocejo
Happy to share our collaboration led by @jsmithymd across 14 international centers on this study of ICI after progression on TIL in advanced #melanoma.
➡️Post-TIL ICI activity was limited, with ORR 11% and median OS 8.8 months, underscoring the need for novel trials in this setting.
[Quoting @jitcancer: New #JITC short report: "Immune checkpoint inhibitor therapy after tumor-infiltrating lymphocytes in unresectable melanoma" https://t.co/6bZ7SPPNsw
@DrBetofMDPhD @ShirlyGrynberg @ajsfurness @ja_ocejo @bbuchbinderMD @LutzkyJose
@evanlipson @DoniaMarco @HaanenJohn https://t.co/LVJ5MrT94D]
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Marco Donia @DoniaMarco
❓What are the outcomes of checkpoint inhibitors after progression to TIL therapy in #melanoma?
👇Check the work led by the brilliant James Smithy of @MSKCancerCenter with multiple international groups including our team at @CCITdk
[Quoting @jitcancer: New #JITC short report: "Immune checkpoint inhibitor therapy after tumor-infiltrating lymphocytes in unresectable melanoma" https://t.co/6bZ7SPPNsw
@DrBetofMDPhD @ShirlyGrynberg @ajsfurness @ja_ocejo @bbuchbinderMD @LutzkyJose
@evanlipson @DoniaMarco @HaanenJohn https://t.co/LVJ5MrT94D]
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VJ Oncology @VJOncology
Omid Hamid (@OmidHamidMD) at #ASCO26 at discusses from a Phase I/II trial evaluating prior anti-CTLA-4 blockade on subsequent #immunotherapy response in anti-PD-1 refractory metastatic malignant #melanoma 🧪 Prior anti-CTLA-4 treatment was associated with immune suppression and worse survival outcomes 💉📉
Watch: https://t.co/UWRJ5qDpds
#ImmunoOnc @ASCO #TrialUpdate #MelSM #SkcSM
This video is available on the Skin Cancer Channel on VJOncology, an independent medical education platform, which is supported by Replimune. Supporters have no influence over the production of content.
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