Ankit Mangla, Co-Director Melanoma, Cutaneous Oncology and Sarcoma Disease team at University Hospitals Seidman Cancer Center, shared on LinkedIn:
“Chemotherapy has largely fallen out of favor in metastatic melanoma.
With immune checkpoint inhibitors, BRAF/MEK inhibitors, and now TIL therapy, that shift makes sense.
National guidelines are clear that clinical trials should be the first choice for patients with relapsed-refractory melanoma (RRM).
But what happens when a trial isn’t an option?
Woo Kyung Doolittle reviewed 10 patients with RRM who received a modified vinblastine-cisplatin-temozolomide (mVCT) regimen at SEIDMAN CANCER CENTER AT UNIVERSITY University Hospitals because they could not enroll in a trial.
The reasons were telling (the usual suspects):
- Active brain metastasis (80%)
- History of Grade 3/4 immunotherapy toxicity (60%)
- Acral or mucosal histology (50%)
- Social barriers such as insurance, transportation, and performance status (40%)
The results:
- ORR 50%, clinical benefit rate 70%
- Intracranial response rate 62.5%, with 100% intracranial clinical benefit
- Median PFS 7 months, median OS 22 months
- Grade ≥3 toxicity in four patients, with two dose reductions and one discontinuation Two patients who progressed on mVCT later enrolled in phase 1 trials, and others went on to TIL therapy or immunotherapy.
Why temozolomide?
It crosses the blood-brain barrier and may also reduce immunosuppressive regulatory T cells.
One study found that low-dose TMZ cut circulating Foxp3+ Tregs by 60%, and TMZ plus ipilimumab achieved a ~30% response rate. This suggests it may complement immunotherapy, though more data are needed.
Our takeaway is not that chemotherapy should replace innovation.
TIL therapy and trials remain the goal, but access is limited.
TIL referral-to-infusion can average over 100 days, and rapid progression during that window can be fatal.
Chemotherapy is accessible, steroids don’t blunt its activity, and TMZ crosses the blood-brain barrier. For the right patient, mVCT can bridge the gap.
This small, retrospective, single-center study may provide a framework for a bridging regimen for patients waiting for TILs (between harvest, manufacturing, and the start of lymphodepletion).
It also underscores something bigger: we must work to broaden trial eligibility and address the social barriers that keep patients out.
Title: Utility of Chemotherapy for Metastatic Melanoma in the Contemporary Era and Experience with Modified Vinblastine–Cisplatin–Temozolomide at a Tertiary Care Center
Authors: Woo Kyung Lee Doolittle, Rohit Rao, Malena Johnson, Felicia Tejawinata, Akihiro Yoshida, Luke Daniel Rothermel, Ankit Mangla.
Read The Full Paper.”
You can also read: Yago Garitaonaindía: A Framework to Quantify the Efficacy–effectiveness Gap in First-line Metastatic Melanoma
