The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma

BackgroundMAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response.MethodsSix metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation.ResultsCompared to patients with wild-type MAP2K1/2, those with MAP2K1/2 mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between MAP2K1/2 mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with MAP2K1/2 mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with MAP2K mutation was enriched in CD8+ T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with MAP2K1/2 mutations from anti-CTLA-4 treatment.ConclusionsMAP2K1/2 mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with MAP2K1/2-mutated melanoma.

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The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21587 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21587-e21587

Author(s):

Ting Ye ◽

Jieying Zhang ◽

Xinyi Liu ◽

Mengmei Yang ◽

Yuhan Zhou ◽

...

Keyword(s):

Overall Survival ◽

Predictive Value ◽

Cox Regression ◽

Treatment Options ◽

Objective Response ◽

Progression Free Survival ◽

Driver Mutations ◽

Cox Regression Analysis ◽

Melanoma Patients ◽

The Impact

e21587 Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.

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Prior Therapy With Pegylated-Interferon Alfa-2b Improves the Efficacy of Adjuvant Pembrolizumab in Resectable Advanced Melanoma

Frontiers in Oncology ◽

10.3389/fonc.2021.675873 ◽

2021 ◽

Vol 11 ◽

Author(s):

Dong-Dong Jia ◽

Yanling Niu ◽

Honglin Zhu ◽

Sizhen Wang ◽

Tonghui Ma ◽

...

Keyword(s):

Adjuvant Therapy ◽

Cox Regression ◽

Objective Response ◽

Pegylated Interferon ◽

Recurrence Rates ◽

Cox Regression Analysis ◽

Prior Therapy ◽

Kaplan Meier ◽

Melanoma Patients ◽

The Impact

Combination immunotherapy can overcome the limited objective response rates of PD-1 blockade. Interferon alpha (IFN-α) has been proven to be effective in modulating immune responses and may enhance the clinical responses to PD-1 blockade. According to clinical practice guidelines, IFN-α was recommended as adjuvant therapy for stage IIB/C melanoma patients. However, the impact of prior IFN-α therapy on the efficacy of subsequent PD-1 blockade in melanoma has not been previously reported. Therefore, we performed a retrospective analysis for melanoma patients and addressed whether prior IFN-α therapy enhanced adjuvant pembrolizumab as later-line treatment. Fifty-six patients with resectable stage III/IV melanoma who received adjuvant therapy with pembrolizumab were retrospectively enrolled in this study. Notably, 25 patients received adjuvant pegylated IFN-α (PEG-IFN-α) in the prior line of treatment while 31 patients did not receive prior PEG-IFN-α therapy. Cox regression analysis showed that prior PEG-IFN-α therapy was associated with the efficacy of later-line adjuvant pembrolizumab (hazard ratio=0.37, 95% CI 0.16-0.89; P = 0.026). The recurrence rates after treatment with adjuvant pembrolizumab were significantly reduced in the prior PEG-IFN-α group (P < 0.001). The Kaplan-Meier analysis also showed that recurrence-free survival (RFS) after adjuvant pembrolizumab therapy was prolonged by prior PEG-IFN-α treatment (median RFSPem 8.5 months vs. 4.5 months; P = 0.0372). These findings indicated that prior PEG-IFN-α could enhance the efficacy of adjuvant pembrolizumab. The long-lasting effects of PEG-IFN-α provide a new rationale for designing combination or sequential immunotherapy.

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Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

Hepatology International ◽

10.1007/s12072-021-10151-4 ◽

2021 ◽

Author(s):

Maaike Biewenga ◽

Monique K. van der Kooij ◽

Michel W. J. M. Wouters ◽

Maureen J. B. Aarts ◽

Franchette W. P. J. van den Berkmortel ◽

...

Keyword(s):

Overall Survival ◽

Liver Metastasis ◽

Combination Therapy ◽

Real World ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Negative Effect ◽

Melanoma Patients

Abstract Background Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort. Methods Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3–4 hepatitis and outcome. Results 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). Conclusion Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome.

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Immune checkpoint inhibitors (ICI) in advanced upper tract and lower tract urothelial carcinoma (UC): A comparison of outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.406 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 406-406

Author(s):

Stepan M. Esagian ◽

Ali Raza Khaki ◽

Lucia Carril-Ajuria ◽

Joseph J. Park ◽

Mehmet Asim Bilen ◽

...

Keyword(s):

Primary Tumor ◽

Cox Regression ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Clinical Trial Data ◽

Progression Free Survival ◽

Tumor Location ◽

Outcome Data ◽

Similar Response ◽

Mixed Histology

406 Background: Despite anatomical and biological differences, upper and lower tract UC (UTUC; LTUC) are usually managed similarly. Modern era clinical trial data comparing their outcomes with ICI are conflicting. We hypothesized that response and outcomes would be similar in patients (pts) with advanced UTUC and LTUC. Methods: We performed a retrospective cohort study collecting demographic, clinicopathologic, treatment, and outcome data for pts with advanced UC receiving ICI (2013-2020) across 24 centers (US; Europe). We compared objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between pts with UTUC and LTUC. Uni- / multi- variable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Stratified subgroup analyses were performed according to histology (pure, mixed) and line of treatment (first-line, subsequent). Results: A total of 984 pts were identified, and 707, 717, and 738 were included in ORR, OS, and PFS analyses, respectively. After exclusions, the UTUC group comprised of 130 pts (vs. 616 in LTUC) with median age 71 (40-92) (vs. 70 [32-93]), 62% men (vs. 76%), 41% never smokers (vs. 29%), 62% with history of prior radical surgery for primary tumor (vs. 52%), and 29% with liver metastases (vs. 18%). Table shows results of ORR, OS, and PFS analyses. In the overall population, pts with UTUC and LTUC receiving ICI had comparable ORR, OS, and PFS. Pts with mixed-histology UTUC had significantly lower ORR (adjusted OR 0.20, 95%CI 0.05-0.91) and shorter PFS (adjusted HR 1.66, 95%CI: 1.06-2.59) vs. mixed-histology LTUC. Conclusions: Pts with advanced UTUC and LTUC receiving ICI have similar response and outcomes, except for pts with mixed-histology UTUC vs LTUC. Subset analysis of primary tumor location in ongoing clinical trials can validate our data, while biomarker work is ongoing. [Table: see text]

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Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer

Cells ◽

10.3390/cells9092071 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2071

Author(s):

Jihane Boustani ◽

Valentin Derangère ◽

Aurélie Bertaut ◽

Olivier Adotevi ◽

Véronique Morgand ◽

...

Keyword(s):

Rectal Cancer ◽

Tumor Regression ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Locally Advanced ◽

Progression Free Survival ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Tumor Regression Grade ◽

The Impact

In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0–17) and 0.5 (range, 0–27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.

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The solved and unresolved issues of melanoma staging: A comparison of American Joint Committee on Cancer (AJCC) 7th versus 8th edition.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.9578 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 9578-9578

Author(s):

Shirin Bajaj ◽

Anthony Collado ◽

Una Moran ◽

Douglas MacArthur Donnelly ◽

Paul Johannet ◽

...

Keyword(s):

Cox Regression ◽

Primary Melanoma ◽

Progression Free Survival ◽

Stage I ◽

Added Value ◽

Stage Iii ◽

Melanoma Patients ◽

Ajcc Staging ◽

The Impact ◽

8Th Edition

9578 Background: The recently revised (AJCC) Staging Manual, 8th edition, introduced changes including removal of mitotic index and addition of the IIID substage. There is active debate on the utility of this revision, especially, without the inclusion of a novel prognostic biomarker, during an era of major therapeutic shifts and amidst accrual of adjuvant clinical trials for high-risk resected primary melanoma. We examined whether re-staging primary melanoma patients using the new AJCC 8 system yielded improved prognostication as compared to AJCC 7. Methods: We compared the impact of changes in staging criteria in stage I-III melanoma patients who were prospectively enrolled in a NYU clinicopathological database between January 2010 and December 2016 with active protocol-driven follow up (FU). We assessed primary tumor category (T) and nodal status (N) according to both AJCC 7 and 8. Progression free survival (PFS) and overall survival (OS) curves were generated for both editions and then stratified by substage. We analyzed discordance using Cox Regression Models. Results: 1,379 patients (56% male, mean thickness 1.6, median FU 34.8 months) were included in the analyses. All but one patient remained in the same ‘major’ stage using AJCC 7 and 8 (stage I- 998; II- 224, 225; III- 157, 156) whereas 44% of stage III substage classifications were discordant comparing AJCC 7 to 8. Despite removing mitoses as a criterion for Stage I, there was no significant change between editions in PFS/OS when evaluating major and substages of stage I. Stage IIC patients had worse PFS/OS than stage IIIA patients in AJCC 8 (PFS p = 0.04, OS p = 0.02). AJCC 8, which implemented four rather than three substages, had improved PFS prognostication (c-index = 0.59 vs 0.66, p = 0.05 for AJCC 7 vs 8). Conclusions: Our results reinforce the added value of AJCC 8 compared to 7, as removing an operator dependent variable is more practical for stage I, and increased influence of thickness/ulceration and the addition of a new substage is more prognostically informative for stage III. Nevertheless, the poor prognosis of stage IIC patients, despite nodal negative disease, continues to be an unaddressed gap within our current staging framework.

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Effect of antibiotic use prior to or concurrent with immune checkpoint inhibitors on outcomes in patients with Hodgkin lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.8030 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 8030-8030

Author(s):

Steven R Hwang ◽

Alexandra Higgins ◽

Betsy LaPlant ◽

Matthew J. Maurer ◽

Stephen M. Ansell ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Cox Regression ◽

Checkpoint Inhibitors ◽

Retrospective Chart Review ◽

Progression Free Survival ◽

Antibiotic Use ◽

Patient Specific ◽

Cox Regression Analysis

8030 Background: There is growing interest in the identification of modifiable patient-specific factors that may predict response to immune checkpoint inhibitors (ICIs) in classical Hodgkin lymphoma (cHL). Recently, it has been proposed that antibiotic use could decrease the efficacy of ICIs in the treatment of advanced solid malignancies. The objective of our study is to assess whether antibiotic use prior to or concurrent with ICIs is associated with changes in outcomes in patients with cHL. Methods: Patients who received a PD-1 or CTLA-4 blocker for the treatment of cHL at Mayo Clinic Rochester between January 1, 2011 and October 20, 2018 were identified. We conducted a longitudinal retrospective chart review to identify those who received antibiotics within 30 or 90 days prior to initiation or concurrent with ICI therapy. Univariate cox regression analysis was used to assess for an association between antibiotic use and overall survival (OS) and progression-free survival (PFS) within these groups; a time-dependent variable was used for concurrent antibiotic use. Results: A total of sixty-two patients were identified (61% male, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 38 months (range: 4-78). Twenty-one patients (34%) received antibiotics within 90 days of initiation of ICI, of which thirteen (21%) received antibiotics within 30 days. Thirty-five patients (57%) received antibiotics concurrently with ICI. Concurrent and prior antibiotic use within 90 days of ICI were both associated with inferior PFS (concurrent HR = 6.38 [95% CI 3.02-13.47]; 90-day HR = 2.21 [95% CI 1.10-4.47]) and OS (concurrent HR = 8.77 [95% CI 1.91-40.36]; 90-day HR = 2.96 [95% CI 1.09-8.04]). Conclusions: Antibiotic use is associated with inferior outcomes in patients with cHL treated with ICIs in this single institution cohort. This may reflect potential antibiotic effects on the gut microbiome (GMB) and immune system as has been suggested in prior studies. Further confirmatory studies and examination of potential confounding covariates are needed.

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Ovarian Cancer Risk Scores Based on Immune-Related Pseudogenes to Predict Overall Survival and Guide Immunotherapy and Chemotherapy

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/1586312 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Jie Zhao ◽

Rixiang Zhao ◽

Xiaocen Wei ◽

Xiaojing Jiang ◽

Fan Su

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

High Risk ◽

Cox Regression ◽

High Risk Group ◽

The Cancer Genome Atlas ◽

Risk Scores ◽

Ovarian Cancer Risk ◽

Cox Regression Analysis ◽

The Impact

Background. Ovarian cancer (OC) is the top of the aggressive malignancies in females with a poor survival rate. However, the roles of immune-related pseudogenes (irPseus) in the immune infiltration of OC and the impact on overall survival (OS) have not been adequately studied. Therefore, this study aims to identify a novel model constructed by irPseus to predict OS in OC and to determine its significance in immunotherapy and chemotherapy. Methods. In this study, with the use of The Cancer Genome Atlas (TCGA) combined with Genotype-Tissue Expression (GTEx), 55 differentially expressed irPseus (DEirPseus) were identified. Then, we constructed 10 irPseus pairs with the help of univariate, Lasso, and multivariate Cox regression analysis. The prognostic performance of the model was determined and measured by the Kaplan–Meier curve, a time-dependent receiver operating characteristic (ROC) curve. Results. After dividing OC subjects into high- and low-risk subgroups via the cut-off point, it was revealed that subjects in the high-risk group had a shorter OS. The multivariate Cox regression performed between the model and multiple clinicopathological variables revealed that the model could effectively and independently predict the prognosis of OC. The prognostic model characterized infiltration by various kinds of immune cells and demonstrated the immunotherapy response of subjects with cytotoxic lymphocyte antigen 4 (CTLA4), anti-programmed death-1 (PD-1), and anti-PD-ligand 1 (PD-L1) therapy. A high risk score was related to a higher inhibitory concentration (IC50) for etoposide ( P = 0.0099 ) and mitomycin C ( P = 0.0013 ). Conclusion. It was the first study to identify a novel signature developed by DEirPseus pairs and verify the role in predicting OS, immune infiltrates, immunotherapy, and chemosensitivity. The irPseus are vital factors predicting the prognosis of OC and could act as a novel potential treatment target.

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Comprehensive Analysis and Prognosis Prediction of N6-methyladenosine-related Lncrnas in Immune Microenvironment Infiltration of Gastric Cancer

10.21203/rs.3.rs-1021150/v1 ◽

2021 ◽

Author(s):

Jianfeng Huang ◽

Wenzheng Chen ◽

Changyu Chen ◽

Tao Xiao ◽

Zhigang Jie

Keyword(s):

Gastric Cancer ◽

Risk Model ◽

Cox Regression ◽

Cytotoxic T Lymphocyte ◽

The Cancer Genome Atlas ◽

Risk Scores ◽

Rna Modification ◽

Consensus Clustering ◽

Immune Microenvironment ◽

Cox Regression Analysis

Abstract BackgroundN6-methyladenosine (m6A) RNA modification plays an important role in regulating tumor microenvironment (TME) infiltration. However, the relationship between the expression pattern of m6A-related long non-coding RNAs (lncRNAs) and the immune microenvironment of gastric cancer (GC) is unclear. MethodsIn this study, 23 m6A-related lncRNAs were identified by Pearson’s correlation analysis and univariate Cox regression analysis. According to the expression of these lncRNAs, we identified two distinct molecular clusters by consensus clustering and compared the differences of the TME and enriched pathways between the two clusters. We further constructed a prognostic risk signature and verified it using The Cancer Genome Atlas training and testing cohorts. ResultsThe results showed that cluster 1 was associated with tumor-related and immune activation-related pathways. In addition, cluster 1 was also associated with higher ImmuneScore, StromalScore, and ESTIMATEScore. The results of the stratified survival analysis and independent prognosis analysis indicated that the risk signature is an independent prognostic indicator for patients with GC. In addition, it can effectively predict survival status in patients with different clinical characteristics. Furthermore, our risk model showed that low risk scores were significantly correlated with high expression of programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), as well as sensitivity to chemotherapeutic drugs (e.g., paclitaxel and oxaliplatin). ConclusionsThis evidence contributes to our understanding of the regulation of TME infiltration by m6A-related lncRNAs and my lead to more effective immunotherapy and chemotherapy for patients with GC.

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Impact of immunotherapy on survival differences in patients with melanoma and chronic lymphocytic leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21550 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21550-e21550

Author(s):

Raghav Tripathi ◽

Jeremy S. Bordeaux ◽

Luke Rothermel ◽

Ankit Mangla

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Cox Regression ◽

Checkpoint Inhibitors ◽

Lymphocytic Leukemia ◽

Average Survival ◽

Melanoma Patients ◽

The Difference ◽

Survival Differences ◽

The Impact ◽

Hispanic White

e21550 Background: Chronic lymphocytic leukemia (CLL) is well known to be associated with secondary malignancies like melanoma. Patients with melanoma and CLL are known to have poorer prognosis compared to patients without CLL. Checkpoint inhibitors (CPI) started gaining traction in 2011 after ipilimumab approval and are widely used in treatment of advanced melanoma. The objective of this study is to determine the survival of patients with melanoma and CLL in the era of CPI (2011 onwards) compared to previous years. Methods: We identified patients with melanoma and CLL reported to the Surveillance, Epidemiology, and End Results (SEER-18) program. We created cohorts of patients with melanoma and CLL vs. melanoma without CLL and split the cohorts into patients diagnosed from 2000-2010 and 2011-2017 to evaluate the impact of immunotherapy on overall all-cause survival. Kaplain-Meier survival curves were created for each of the four cohorts using the Ederer/direct-adjusted survival method. Standard Cox regression models adjusted for age and sex used to compare survival between subgroups. Two-sided p-values < 0.05 were considered significant. Results: From 2000-2017, 536,264 patients with melanoma were included in this study. 2,945 [0.55%] patients had coexisting CLL. Most patients were male (303,477 [56.6%]), age 60-79 (235,833 [44.0%]), non-Hispanic white (499,151 [93.08%]), and diagnosed from 2000-2010 (285,292 [53.2%]) with melanoma of the trunk (156,722 [29.2%]). From 2000-2010, patients with melanoma had an average survival of 91.4 months (95% CI 88.7-94.1) and those with coexisting CLL had an average survival of 59.3 months (95% CI 58.1-60.6). From 2011-2017, patients with melanoma had an average survival of 129.1 months (95% CI 127.7-130.5) and those with coexisting CLL had an average survival of 116.0 months (95% CI 113.5-118.5). The difference in survival in patients with melanoma vs. melanoma and CLL in 2000-2010 (32.1 months) is significantly greater than that of patients from 2011-2017 (13.1 months, p < 0.05). Conclusions: Although CLL continues to confer a survival disadvantage in patients with melanoma, the survival of patients with CLL and melanoma is better in the CPI-era. We also demonstrate that in the CPI era the gap between the survival of patients with melanoma and CLL and melanoma alone is also reducing significantly.

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