Immune checkpoint inhibition therapy for advanced skin cancer in patients with concomitant hematological malignancy: a retrospective multicenter DeCOG study of 84 patients

Abstract

BackgroundSkin cancers are known for their strong immunogenicity, which may contribute to a high treatment efficacy of immune checkpoint inhibition (ICI). However, a considerable proportion of patients with skin cancer is immuno-compromised by concomitant diseases. Due to their previous exclusion from clinical trials, the ICI treatment efficacy is poorly investigated in these patients. The present study analyzed the ICI treatment outcome in advanced patients with skin cancer with a concomitant hematological malignancy.MethodsThis retrospective multicenter study included patients who were treated with ICI for locally advanced or metastatic melanoma (MM), cutaneous squamous cell carcinoma (cSCC), or Merkel cell carcinoma (MCC), and had a previous diagnosis of a hematological malignancy irrespective of disease activity or need of therapy at ICI treatment start. Comparator patient cohorts without concomitant hematological malignancy were extracted from the prospective multicenter skin cancer registry ADOREG. Treatment outcome was measured as best overall response, progression-free (PFS), and overall survival (OS).Results84 patients (MM, n=52; cSCC, n=15; MCC, n=17) with concomitant hematological malignancy were identified at 20 skin cancer centers. The most frequent concomitant hematological malignancies were non-Hodgkin’s lymphoma (n=70), with chronic lymphocytic leukemia (n=32) being the largest entity. While 9 patients received ICI in an adjuvant setting, 75 patients were treated for advanced non-resectable disease (55 anti-PD-1; 8 anti-PD-L1; 5 anti-CTLA-4; 7 combinations). In the latter 75 patients, best objective response (complete response+partial response) was 28.0%, disease stabilization was 25.3%, and 38.6% showed progressive disease (PD). Subdivided by skin cancer entity, best objective response was 31.1% (MM), 26.7% (cSCC), and 18.8% (MCC). Median PFS was 8.4 months (MM), 4.0 months (cSCC), and 5.7 months (MCC). 1-year OS rates were 78.4% (MM), 65.8% (cSCC), and 47.4% (MCC). Comparison with respective ADOREG patient cohorts without hematological malignancy (n=392) revealed no relevant differences in ICI therapy outcome for MM and MCC, but a significantly reduced PFS for cSCC (p=0.002).ConclusionsICI therapy showed efficacy in advanced patients with skin cancer with a concomitant hematological malignancy. Compared with patients without hematological malignancy, the observed ICI therapy outcome was impaired in cSCC, but not in MM or MCC patients.

Does immune checkpoint inhibitor increase the risks of poor outcomes in COVID-19-infected cancer patients? A systematic review and meta-analysis

“…In addition, early hypotheses postulated that ICI may worsen COVID-19 outcomes due to potential immune hyperactivation [ 44 – 46 ], where they may upregulate pro-inflammatory cytokines [ 44 , 45 ] and over-activate CD8 T-cells[ 46 ]—resulting in the dysregulation and exhaustion of T-cells [ 44 , 47 ]. This hypothesis was supported by the fact that severe COVID-19 cases were associated with lymphopenia and immune hyperactivity [ 6 , 45 ], thus suggesting that ICI may synergistically exacerbate cytokine storm in COVID-19 infection [ 46 ].…”

Risk of Infection with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis

“…In the pandemic era, caution should be used particularly with those patients at risk of COVID-19 infection and mortality when ICI combinations or a CT + ICIs combination is planned in cancer patients. Despite this, larger studies are urgently needed to improve the evaluation of the effects of ICIs in patients with COVID-19 and the use of ICIs during the coronavirus pandemic [ 47 , 48 ].…”

Immunotherapy use outside clinical trial populations: never say never?

“…ICI experience in those patients is limited; however, in a recent retrospective study of ICI in patients with non-resectable skin cancer and concomitant haematological malignancy [most commonly CLL (38%)], ORR was 31.8% (14/44) for melanoma, 18.8% (3/16) for Merkel cell carcinoma, and 26.7% (4/15) for squamous cell carcinoma (SCC), with survival outcomes similar to those observed in a real-world immune-competent cohort, except for SCC, where they were lower. 53 ICIs are also an emerging treatment strategy for CLL itself, with early trials of anti-PD-1 suggesting activity in patients with Richter transformation, with overall acceptable toxicity. 54,55 Immunocompromised state can also result from chronic immunosuppressive treatments, such as those received by transplant recipients.…”