Immune checkpoint inhibitor (ICI) therapy duration

Multiple retrospective studies have examined the optimal duration of first line immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer.^3-4 In this retrospective real-world study, EUMelaReg (Abstract #9531) researchers evaluated the EUMelaReg treatment registry for the optimal length of ICI treatment after partial or complete remission from ICI treatment for metastatic melanoma.⁵  

The study assessed the treatment duration for either a single agent ICI (ex. Keytruda^® (pembrolizumab), etc), (71%) or ICI combined with anti-CTLA4 (ex. Yervoy^® [ipilimumab], etc.) (29%) as first line in patients with the best overall partial (PR) and complete responses (CR). PFS and OS were the primary outcomes.

Patients were stratified according to treatment duration once PR or CR were achieved and cloned to account for time bias. A total of 1,291 patients were included in the analysis. For patients with partial response, PFS and OS were significantly improved with maintenance ICI of greater than 12 months or until progression. For patients achieving complete response, ICI greater than 12 months did not seem to impact PFS and may slightly OS improvement.

Based on multiple retrospective studies in various cancers, response may be used to determine optimal ICI duration. However, prospective studies are needed to assert optimal ICI duration.

Melanoma

IOV-COM-202: Cohort 1A (Abstract #9505) is a phase 2 expansion cohort (n=23) for Amtagvi™ (lifileucel) combined with the ICI, pembrolizumab, in ICI-naïve unresectable or metastatic melanoma. The treatment consists of the following:

• Step 1: pembrolizumab
• Step 2: lymphodepleting chemotherapy
• Step 3: lifileucel cells with interleukin 2 (up to 6 doses) to promote cell expansion in the body
• Step 4: pembrolizumab for up to 2 years or progressive disease or intolerable side effects⁶

The primary endpoints were objective response rate (ORR) and incidence of grade ≥3 treatment-emergent adverse events. The CR 22.7% (5/22) and PR 40.9% (9/2) yielded a confirmed ORR of 63.6% (14/22) while 6 pts (27.3%) had stable disease. Median time to initial response was 2.5 months. No new adverse events were reported.

Of the National Comprehensive Cancer Network (NCCN) category 1 immune-oncology agents recommended to treat melanoma, NCCN prefers combination drugs such as Opdualag™ (nivolumab and relatimab) and OPDIVO^® (nivolumab) combined with ipilimumab over single agent ICI such as pembrolizumab and nivolumab as first line therapy. ⁷

In this study, ICI is combined with lifileucel as a first-line therapy, leading to concerns about sequencing subsequent therapy. Are we using the most effective therapies all at once, leaving patients with limited subsequent options?

The total cost for this therapy is high. The estimated total wholesale acquisition cost (WAC) for drug therapy is (lifileucel $515,000; pembrolizumab $386,000 for 2 years) $900,000 and does not include the cost of lymphodepleting chemotherapy, interleukin 2, and inpatient admission for administration and side effect management. ⁸

Prophylactic tocilizumab 

MajesTEC-1 Prophylactic tocilizumab (Abstract 7517), a phase 1/2 study evaluates the use of prophylactic Actemra^® (tocilizumab) prior to the first Tecvayli^® (teclistamab) step-up dose.⁹ Currently, tocilizumab is FDA indicated for the treatment of chimeric antigen receptor T-cell mediated cytokine release syndrome (CRS).¹⁰

In this study, patients with triple-class exposed relapsed refractory multiple myeloma (n=24) received prophylactic tocilizumab 8mg/kg and CRS incidence, severity, time to onset, and duration were assessed.⁹

Of the 24 patients who received prophylactic tocilizumab, CRS incidence was reduced for all grades with no grade 3 or greater CRS incidents. In the overall MajesTEC-1 group CRS greater than or equal to grade 3 was rare, 0.6%. With subsequent teclistamab dosing, CRS recurred in 13% of patients in the prophylactic group and none in the overall MajesTEC-1 group. Both groups had the same CRS onset and duration with no new new toxicities observed.⁹

With a WAC price of $55,241 for a 200mg one time dose of intravenous Actemra, a risk benefit assessment is needed to determine if prophylactic dosing is optimal.

With ongoing research, advancements in cancer management will continue to change how we treat these diseases.