Responses to immune checkpoint inhibitors in nonagenarians

Johnpulle, Romany; Conry, Robert M.; Sosman, Jeffrey A.; Puzanov, Igor; Johnson, Douglas B.

doi:10.1080/2162402x.2016.1234572

Cited by 24 publications

(18 citation statements)

References 39 publications

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“…In this population, we found that TVEC was well-tolerated and had a higher-than- 16,17 Our study finds that patients older than 75 responded similarly to TVEC therapy as those younger than 75. This recapitulates other studies showing that response to immunotherapies is not hampered by advanced age 18,19 and may even be enhanced 20 in the setting of decreased T regulatory cells.…”

Section: F I G U R E 1 Swimmer's Plot For Progression-free Survival (supporting

confidence: 90%

Correlates of response and outcomes with talimogene laherperpvec

Zhou

Wang

McKee

et al. 2019

Journal of Surgical Oncology

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Background and Objectives Patients with in‐transit or limited cutaneous metastatic melanoma may benefit from intralesional injections with talimogene laherparepvec (TVEC), a modified oncolytic herpesvirus. However, its use in patients with adverse prognostic scores in a real‐life clinical setting has not been studied. Methods We performed a two‐center retrospective analysis of 40 patients with metastatic melanoma treated with TVEC from 2015–2017. Demographics, overall response, and survival after therapy were noted. Results Overall, there was a durable response rate of 40%; median progression‐free survival (PFS) was 10.5 months and median overall survival (OS) was not reached. Bulky disease was associated with decreased OS (15.7 months vs not reached, P < .05) and mPFS (2.3 months vs not reached, P < .05), when compared with smaller tumors. Poor performance status (ECOG 2–3) was associated with worse OS (10.2 months vs not reached, P < .05) and PFS (2.1 months vs not reached, P < .05) compared to patients with ECOG 0–1. There was no difference in the outcomes with age greater than 75 or with prior therapies. Adverse events were relatively tolerable. Conclusions These findings demonstrate that TVEC is an effective and safe treatment for metastatic melanoma in a real‐life clinical setting, and suggest parameters to aid in appropriate therapy selection for optimal response.

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Section: F I G U R E 1 Swimmer's Plot For Progression-free Survival (supporting

confidence: 90%

Correlates of response and outcomes with talimogene laherperpvec

Zhou

Wang

McKee

et al. 2019

Journal of Surgical Oncology

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“…A 28% response rate was also recently reported for urothelial bladder carcinoma patients older than 80 years who were treated with atezolizumab (vs 23% for all patients) . We have also reported cases of clinical benefit and response in patients older than 90 years, including a 90‐year‐old treated with a combination of ipilimumab and nivolumab who experienced a complete response and a 95‐year‐old with a partial response after pembrolizumab . We think that old age is not a contraindication to immune checkpoint inhibition and instead that functional status is a more relevant consideration.…”

Section: Extremes Of Agesupporting

confidence: 70%

“…46 We have also reported cases of clinical benefit and response in patients older than 90 years, including a 90-year-old treated with a combination of ipilimumab and nivolumab who experienced a complete response and a 95-year-old with a partial response after pembrolizumab. 53 We think that old age is not a contraindication to immune checkpoint inhibition and instead that functional status is a more relevant consideration. However, the overall toxicity profile, efficacy, and relative risks and benefits in comparison with other therapies have not been studied comprehensively for tumor types other than melanoma, and they will need further study.…”

Section: Extremes Of Agementioning

confidence: 99%

Immune checkpoint inhibitors in challenging populations

Johnson

Sullivan

Menzies

2017

Cancer

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Immune checkpoint inhibitors, including those targeting the PD-1/PD-L1 and CTLA-4 pathways, are revolutionizing cancer therapeutics. Both activity and toxicities largely stem from unleashing tumor- or host-specific cytotoxic T cells. Many patients seen in routine clinical practice did not qualify for, or were seriously underrepresented in immune checkpoint inhibitor clinical trials. Thus, a major gap in knowledge regarding the safety and efficacy of these agents persists in many populations, even following regulatory approval. To address this challenge, we aggregated and synthesized the available pre-clinical and clinical data surrounding immune checkpoint inhibitor therapy in challenging clinical populations to assist treatment decision making for both academic and community oncologists. Specifically, we focus on the safety and activity of immune checkpoint inhibitors in patients with autoimmune disorders, post-organ transplant, chronic viral infections, ongoing immunosuppressant use, organ dysfunction, pregnancy, brain metastases, extremes of age, and impaired functional status.

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“…However, these small subgroups of patients were usually not analyzed separately. A series of 3 nonagenarian melanoma patients treated in two centers with immune checkpoint inhibitors was published in 2016 [11]. Two of these 3 patients had a primary mucosal melanoma (one nasal and the other anal).…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab for Unresectable or Metastatic Melanoma in Patients Older than 85 Years of Age

et al. 2019

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Background: Programmed cell death protein-1 (PD-1) inhibitors (pembrolizumab and nivolumab) have been approved for the treatment of advanced melanoma. Over the past decades, patients older than 85 years represent an expanding group of patients in developed countries. In France, 25% of melanomas are diagnosed in patients older than 75 years. Objective: To perform a monocentric retrospective study of patients older than 85 years and treated with pembrolizumab for unresectable or metastatic melanoma in order to evaluate tolerance and potential benefits of this immunotherapy. Methods: Medical records of patients treated with the PD-1 inhibitor pembrolizumab between January 2015 and January 2018 were reviewed. Results: Nine patients (6 women and 3 men) older than 85 years were included in the study. The mean age was 89.6 (85–97) years at inclusion. All patients were PS 0 or 1. The mean number of infusions was 4 (1–12). However, most patients were not able to tolerate the 4-infusion schedule. One patient refused the second infusion for personal reasons. Seven patients had grade 3 or 4 treatment-related adverse events. Conclusion: These results indicate that pembrolizumab treatment in patients older than 85 years may induce responses but is associated with a high risk of toxicity and impaired autonomy.

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Responses to immune checkpoint inhibitors in nonagenarians

Cited by 24 publications

References 39 publications

Correlates of response and outcomes with talimogene laherperpvec

Correlates of response and outcomes with talimogene laherperpvec

Immune checkpoint inhibitors in challenging populations

Pembrolizumab for Unresectable or Metastatic Melanoma in Patients Older than 85 Years of Age

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