Friday, May 27, 2016

ASCO 2016 - immunotherapy after HD IL-2 and vice versa - HD IL-2 after anti-PD1

Update on the overall survival of patients with metastatic melanoma treated with immune checkpoint blockade following initial treatment with HD IL-2.  ASCO 2016.  # e21039.  J Clin Oncol 34, 2016.  Wong, Morse, McDermott, et al. 

Background: High-dose interleukin-2 (HD IL-2) and immune checkpoint inhibitors can provide survival benefit in patients with metastatic melanoma (mM). The clinical impact of using these therapies in sequence remains unknown. Herein, we report on the outcomes of sequencing ipilimumab and/or anti-PD-1/PD-L1 therapy after treatment with HD IL-2 using a national IL-2 patient registry, PROCLAIMSM . Methods: Patients were prospectively enrolled into the registry as of 2011 and must have received at least one dose of HD IL-2 for this analysis. Those that received immune checkpoint inhibitors prior to HD IL-2 were excluded. Statistics and survival analysis were performed on datasets as of December 2, 2015. Results: The mOS for all mm patients (n = 273) was 19.4 months, with a median follow-up of 23.1 months. Three groups were further analyzed according to treatment after HD IL-2; no immune checkpoint blockade following HD IL-2 (no ICB, n = 137), HD IL-2 followed by ipilimumab alone (IL-2 then IPI, n = 82), and HD IL-2 followed by anti-PD-1/PD-L1 inhibitors with or without ipilimumab (IL-2 then aPD-1±IPI, n = 54). This latter group, IL-2 then aPD-1±IPI, could have received ipilimumab before or after anti-PD-1/PD-L1. Patients with no ICB, IL-2 then IPI, and IL-2 then aPD-1±IPI achieved a mOS of 14.1, 15.8, and 28.2 months, respectively. The estimated 12-month survival rates were 56%, 64%, and 96%, respectively. No HD IL-2 treatment-related deaths were reported. Conclusions: There was no difference in mOS between patients treated with ipilimumab post HD IL-2 compared to patients with no ICB [no immunotherapy] following HD IL-2. Patients treated with anti-PD-1/PDL-1±IPI showed increased mOS compared to those treated with HD IL-2 alone. These data further support the concept of investigating IL-2 therapy in combination or sequence with newly developed immune checkpoint inhibitors. Clinical trial information: NCT01415167

12 month survival rates:
56% - no immunotherapy after HD IL2
64% - ipi after HD IL2
96% - antiPD1 after HD IL2 with or without ipi

A Prospective Analysis of High-Dose Interleukin-2 (HD IL-2) following PD-1 inhibitor therapy in patients with metastatic melanoma and renal cell carcinoma.  ASCO 2016.  # e21006.  J Clin Oncol 34, 2016.  Buckbinder, Dutcher, Perritt, et al.

Background: PD-1/PD-L1 inhibitors (aPD-1) have demonstrated efficacy in the treatment of metastatic melanoma (MM) and advanced renal cell carcinoma (RCC). HD IL-2 can produce durable responses in a subset of patients and remains a treatment option. As aPD-1 therapy becomes the backbone of mm and RCC treatment it becomes increasingly important to understand whether HD IL-2 is safe and effective following immune checkpoint blockade (ICB). Methods: PROCLAIMSM  is an IL-2 observational registry with more than 40 participating sites consisting of a retrospective (n = 370, locked) and prospective cohort (n greater than 942, on-going). We queried the prospective cohort to identify pts treated with HD IL-2 after aPD-1 and report their safety and efficacy outcomes, compared to pts who had not received any ICB prior to HD IL-2. Results: Within the database, there are currently 16 patients who received aPD-1 prior to HD IL-2 therapy, 12 patients (3 RCC and 9 MM) had sufficient data as of 12/17/2015 to analyze outcome. Of these 12 patients, seven with mm also received ipilimumab and 3 with RCC also received anti-VEGF therapy prior to treatment with HD IL-2. The most common and reversible toxicities reported as the reason(s) to stop dosing for Cycle 1 in the patients who had previously been treated with aPD-1 were hypotension, diarrhea, vomiting, hypoxia, renal failure and arrhythmia. These toxicities were similar to those observed among the 681 HD IL-2 patients without prior ICB. There were no IL-2 related deaths noted in the cohort receiving prior aPD-1. The one year overall survival from HD IL-2 was 76% in patients who previously received aPD-1 versus 74% in patients who had not previously been treated with ICB. The ORR was 8.3% in patients with prior aPD-1 vs. 15% in those without prior ICB. Conclusions: Data from the PROCLAIM database suggests that HD IL-2 remains a treatment option for pts who have had progressive disease after prior PD-1 inhibition. Continued analysis of patients treated with HD IL-2 will help guide the optimal sequence of these immunotherapies.

Interesting that OS was a bit higher in those who had received anti-PD1 THEN IL2, but response rate was better when IL2 was taken BEFORE any immunotherapy.  It seems there is still much to learn.   - c

No comments:

Post a Comment