Melanoma: Advancement in treatment 2021

Updated information of melanoma is presented, especially with recent advancement in treatment.

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When Relatlimab, a LAG3-inhibitor was combined with nivolumab, progression free survival was significantly improved when compared with nivolumab alone:
N Engl J Med 2022; 386:24-34

[stanleykim]

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics, Inc.) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.
Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)
Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

[stanleykim]

On December 3, 2021, the Food and Drug Administration approved pembrolizumab (Keytruda, Merck) for the adjuvant treatment of adult and pediatric (≥12 years of age) patients with stage IIB or IIC melanoma following complete resection.

Efficacy was evaluated in KEYNOTE-716 (NCT03553836), a multicenter, randomized (1:1), double-blind, placebo-controlled trial in patients with completely resected stage IIB or IIC melanoma.

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NADINA: Neoadjuvant Dual Immunotherapy Improves EFS in Stage III Melanoma: ipilimumab + nivolumab Q 3W x 2 before surgery vs. no neoadjuvant Tx

Patients with Stage III melanoma have improved even free survival: The 12-month estimated EFS was 83.7% versus 57.2% (hazard ratio = 0.31; 99.9% CI, 0.15-0.66; P < .0001). For all subgroups, outcomes favored the neoadjuvant therapy combination.
In the neoadjuvant arm, 58% of patients had a major pathologic response, 8% had a pathologic partial-response, 26.4% a pathologic non-response, 2.4% had progression before surgery, and 5.2% were not reported.

[stanleykim]

NADINA trial: Neoadjuvant Dual Immunotherapy Improves EFS in Stage III Melanoma

[stanleykim]

FDA approved Tebentafusp for metastatic uveal melanoma. A randomized study showed Tebentafusp improved 1-yr survival to 73% compared with pembrilozumab or nivolumab (59%).

[stanleykim]

Relatlimab (lymphocyte activation gene 3 inhibitor) and nivolumab combination doubled disease free survival rate when compared with nivolumab alone.
However, overall survival data are not mature yet