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Impact of Age on Outcomes with Immunotherapy for Patients with Melanoma.

ABSTRACT: Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti-PD-1/anti-PD-L1 mAb at two academic medical centers.We retrospectively collected data on all patients with metastatic melanoma treated with anti-PD-1/PD-L1 mAb between May 2009 and April 2015. We used Kaplan-Meier and Cox regression analyses to assess OS and PFS and identify factors associated with these outcomes. We also compared rates of autoimmune toxicity across age groups.Of 254 patients, 57 (22.4%) were <50 years old, 85 (33.5%) were age 50-64, 65 (25.6%) were age 65-74, and 47 (18.5%) were ?75 years. Across age groups, no differences existed in median OS (age <50: 22.9 months, age 50-64: 25.3 months, age 65-74: 22.0 months, age ?75: 24.3 months) or PFS (age <50: 4.1 months, age 50-64: 6.5 months, age 65-74: 5.4 months, age ?75: 7.9 months). The presence of liver metastases and elevated pre-treatment lactate dehydrogenase (LDH) were associated with reduced OS. Presence of liver metastasis, pretreatment LDH, BRAF mutation, and type of melanoma correlated with PFS. Overall, 110 patients (43.3%) experienced immune-mediated toxicities; 25 (9.8%) had colitis and 26 (10.2%) had endocrine toxicity. Rates of colitis, hepatitis, and pneumonitis did not differ across age groups.We demonstrated that patients could safely tolerate anti-PD1/PDL-1 mAb therapy and achieve similar outcomes regardless of their age.Immunotherapy has revolutionized treatment for patients with metastatic melanoma, yet data are lacking regarding the effectiveness and tolerability of these treatments for older patients. In this study, we demonstrated that patients with melanoma safely tolerate immunotherapy and achieve similar outcomes regardless of their age. Specifically, we utilized data from two academic cancer centers and found no significant difference in overall survival, progression free survival, or immune-related toxicities, other than arthritis, across age groups. As the population ages, studies such as this will become critical to help us understand how best to treat older adults with cancer.

SUBMITTER: Betof AS

PROVIDER: S-EPMC5553960 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Impact of Age on Outcomes with Immunotherapy for Patients with Melanoma.

Betof Allison S AS Nipp Ryan D RD Giobbie-Hurder Anita A Johnpulle Romany A N RAN Rubin Krista K Rubinstein Samuel M SM Flaherty Keith T KT Lawrence Donald P DP Johnson Douglas B DB Sullivan Ryan J RJ

The oncologist 20170505 8

<h4>Background</h4>Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti-PD-1/anti-PD-L1 mAb at two academic medical centers.<h4>Methods</h4>We retrospectively collected data on all patients with metastatic melanoma ...[more]

PMID: 28476944

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Project description:BACKGROUND:The benefits of electronic patient reported outcomes (PRO) questionnaires have been demonstrated in many settings, including in hospitals and patient homes. However, it remains to be investigated how melanoma patients and their treating clinicians experience the electronic self-reporting of side effects and the derived communication. OBJECTIVE:The primary objective of this study was to examine patients' and clinicians' experiences with an eHealth intervention for weekly monitoring of side effects during treatment with immunotherapy. METHODS:An eHealth intervention based on questions from the PRO-Common Terminology Criteria for Adverse Events (CTCAE) library was used and tested in a randomized clinical trial with patients receiving immunotherapy for malignant melanoma and clinicians at a university hospital in Denmark. On a weekly basis, patients reported their symptoms from home during the treatment via a provided tablet. The electronic patient reports were available to clinicians in the outpatient clinic. A mixed methods approach was applied to investigate the patients' and clinicians' experiences with the intervention. Data from patient experiences were collected in a short survey, the Patient Feedback Form. Moreover, a subset of the patients participating in the survey was interviewed about their experience. Furthermore, one focus group interview with clinicians was carried out to elucidate their views. RESULTS:A total of 57 patients completed the Patient Feedback Form, and 14 patients were interviewed. The focus group interview included 5 clinicians. Overall, patients and clinicians were satisfied with the tool. They believed it enhanced patients' awareness of side effects and increased their feeling of involvement. The patients reported that it was easy to fill out the questionnaire and that it made sense to do so. However, a minority of the patients expressed in the interviews that they did not believe that the health care professionals had seen their reports when they came to the clinic, and that the reporting did not lead to increased contact with the department. CONCLUSIONS:Overall, satisfaction with the eHealth intervention was high among patients and their treating clinicians. The tool was easy to use and contributed to greater symptom awareness and patient involvement. Thus, in terms of patient and clinician satisfaction with the tool, it makes sense to continue using the tool beyond the project period. TRIAL REGISTRATION:ClinicalTrials.gov NCT03073031; https://tinyurl.com/tjx3gtu.

Project description:BackgroundWe previously reported early on-treatment significant modulation in circulating regulatory T cell (Treg), myeloid derived suppressor cells (MDSC) and antigen-specific type I CD4+ and CD8+ T cells that correlated with clinical outcome in regionally advanced melanoma patients treated with neoadjuvant ipilimumab. Here, we investigated the long term immunologic impact of CTLA4 blockade.MethodsPatients were treated with ipilimumab given at 10 mg/kg IV every 3 weeks for 2 doses bracketing surgery. Blood specimens were collected at baseline and during treatment for up to 9 months. We tested immune responses at 3, 6, and 9 months utilizing multicolor flow cytometry. We compared frequencies of circulating Treg and MDSC on-study to baseline levels, as well as frequencies of CD4+ and CD8+ T cells specific to shared tumor-associated antigens (Gp-100, MART-1, NY-ESO-1).ResultsLevels of Treg significantly increased when measured at 6 weeks following ipilimumab but returned to baseline by 3 months, with no significant difference in Treg levels between relapsed and relapse-free groups at 3, 6 or 9 months. However, lower baseline levels of circulating Treg (CD4+CD25hi+CD39+) were significantly associated with better relapse free survival (RFS) (p = 0.04). Levels of circulating monocytic HLA-DR+/loCD14+ MDSC were lower at baseline in the relapse-free group and further decreased at 6 weeks, though the differences did not reach statistical significance including measurements at 3, 6 or 9 months. We detected evidence of type I (interferon-γ producing), activated (CD69+) CD4+ and CD8+ antigen-specific T cell immunity against cancer-testis (NY-ESO-1) as well as melanocytic lineage (MART-1, gp100) antigens in the absence of therapeutic vaccination. These responses were significantly boosted at 6 weeks and persisted at 3, 6 and 9 months following the initiation of ipilimumab.ConclusionsLower Treg levels at baseline are significantly associated with RFS and increased Treg frequency after CTLA4 blockade was only transient. Lower MDSC was also associated with RFS and MDSC levels were further decreased after ipilimumab. Tumor specific effector immune responses are boosted with CTLA4 blockade and tend to be durable. Trial registration ClinicalTrials.gov Identifier: NCT00972933.

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Impact of Age on Outcomes with Immunotherapy for Patients with Melanoma.

Publications

Impact of Age on Outcomes with Immunotherapy for Patients with Melanoma.

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