Thursday, December 8, 2016

Analysis of IL-2 after ipi in melanoma - and a bit more

IL-2:  An old drug in melanoma, tough to take, recognized to have a response rate around 10%, though about 4-5% of those can be durable.  Now, researchers are looking for ways to use it to improve responses when combined with other drugs.  There was this from 10/2016:  Killing melanoma (in mice) is enhanced in cells treated with reovirus and radiation OR with a combo of tumor-antigen-targeting-antibody, IL-2, anti-PD1 and a T cell vaccine!!!!

Use as an intra-tumoral agent from 7/2016:  Report on intratumoral IL-2 with intratumoral ipi for nonresectable Stage III/IV melanoma 

And this out of ASCO in June:  ASCO 2016 - immunotherapy after HD IL-2 and vice versa - HD IL-2 after anti-PD1 

Now there is this:

A retrospective analysis of High-Dose Interleukin-2 (HD IL-2) following Ipilimumab in metastatic melanoma.  Buchbinder, Gunturi, Perritt, et al.  J Immunother Cancer. 2016 Sep 20.

High dose interleukin-2 (HD IL-2) can induce durable responses in a subset of patients leading to long-term survival. Immune checkpoint blockade (ICB) has demonstrated similarly durable responses in a larger proportion of patients. However, not all patients respond to immune checkpoint blockade and subsequent therapeutic options need to be explored.  The PROCLAIM database was queried for patients with metastatic melanoma who had received HD IL-2 after treatment with ipilimumab or without prior ICB. Patient characteristics, toxicity and efficacy were analyzed.  A total of 52 metastatic melanoma patients were treated with high dose IL-2 after ipilimumab and 276 patients were treated with high dose IL-2 without prior ICB. The overall response rate in the prior ipilimumab group was 21 % as compared to 12 % in the group that had not received prior ipilimumab. The median overall survival, measured from the initiation of HD IL-2 therapy, was 19.3 months in the prior ipilimumab group and 19.4 months in the no prior ICB group. Toxicities observed on HD IL-2 were relatively equivalent between the groups although there were cases of CTLA4 antibody-induced colitis reported after HD IL-2 treatment and a CTLA4 antibody-induced colitis related death.  In this retrospective analysis HD IL-2 therapy displayed antitumor activity in melanoma patients who progressed following treatment with ipilimumab. Most HD IL-2 toxicity was not worsened by prior ipilimumab therapy except for one treatment related death from colitis. Care should be taken to avoid reactivation of CTLA4 antibody-induced colitis.

And this:  

Clinical Response Rates From Interleukin-2 Therapy for Metastatic Melanoma Over 30 Years' Experience: A Meta-Analysis of 3312 Patients.  Bright, Coventry, Eardley-Harris, Briggs.  J Immunother. 2016 Nov 21.    

Interleukin-2 (IL-2), initially used in 1986, can induce clinical regression-complete responses (CR) and partial responses (PR) of metastatic malignant melanoma. IL-2 has been used alone or in combination, and in different dosage schedules, as an immunotherapeutic agent for melanoma treatment. This meta-analysis aimed to document and evaluate the spectrum of reported clinical response rates from the combined experience of almost 30 years of IL-2 clinical usage. Clinical trials using IL-2 for metastatic melanoma therapy that reported: dosage, combinations, study details, definitions and clinical CR, PR, and overall response (OR) rates were included. A meta-analysis was conducted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. In total, 34 studies met inclusion criteria, with 41 separate treatment arms. For all IL-2 treatment modalities collectively, the CR rate was 4.0%, PR 12.5%, and OR 19.7%. CR pre-1994 was 2.7% versus 6.1% post-1994. High and intermediate-IL-2 dosage showed no CR difference, while low-dose IL-2 showed a nonstatistical trend toward an increased CR rate. The highest CR rate resulted from IL-2 combined with vaccine at 5.0%. The meta-analysis showed that IL-2 immunotherapy for advanced metastatic melanoma delivered a CR rate of 4% (range, 0-23%) across nearly 30 years of clinical studies, with gradual improvement over time. The significance is that, contrary to popular belief, the data demonstrated that CR rates were similar for intermediate versus high-IL-2 dosing.

Keep on keeping on, dear ratties!!! - c

No comments:

Post a Comment