Metastatic NSCLC patients in the real world in Finland

501 Background: Since its approval, PD-1/PD-L1 IO therapies are used greatly among patients with mRCC. However, outcomes in the post-IO setting are not well characterized. This study aims to characterize the treatment patterns and clinical outcomes of patients with mRCC who have experienced progression following IO therapy. Methods: A retrospective review of electronic health records from a US community oncology network included patients with mRCC who progressed on their initial IO therapy and received subsequent therapies between 01/01/2018 and 01/31/2023. The index regimen was defined as the therapy administered after the initial IO therapy, and the index date marked the initiation of this index regimen. The index line of therapy (LOT) was defined as the treatment setting in which index regimen was used. Descriptive statistics were used to summarize patient characteristics and treatment patterns. Real-world progression free survival (rwPFS) and overall survival (OS) were analyzed by Kaplan–Meier method. Log-rank tests were performed to compare outcomes across various Index LOTs and index regimen classes. Results: The study identified 299 patients with a median age of 68 years (IQR 60-75). Among them, 72.7% were male, 84.7% were white, and 87.4% had an intermediate/poor risk score according to the international metastatic RCC database consortium. The index regimen was given as follows: 1.7% in first line (1L), 67.9% in 2L, and 30.4% in 3L. Tyrosine kinase inhibitor (TKI) monotherapy was the most common index regimen class (62.2%) with cabozantinib being the most used regimen (46.5%). Over a median follow up of 11.3 months, median (95% CI) rwPFS and OS were 6.0 (5.4, 6.8) and 14.3 (12.1, 16.4) months, respectively. No differences were observed in rwPFS and OS across index LOTs (rwPFS p= 0.763; OS p= 0.885) or index regimen classes (rwPFS p= 0.721; OS p= 0.747, Table 1.). Conclusions: Treatment outcomes in the post-IO setting for mRCC patients are limited. TKI monotherapies are the most common treatments in this setting. No difference was found in OS or rwPFS across index LOTs and index regimen classes. Novel treatments are needed to improve clinical outcomes in these setting. Subgroups N Median rwPFS (95% CI) Median OS (95% CI) Overall 299 6.0 (5.4, 6.8) 14.3 (12.1, 16.4) Index Regimen 2L* 203 6.0 (5.0, 7.1) 14.1 (11.5, 16.3) Index Regimen 3L 91 6.0 (5.1, 8.2) 14.5 (11.6, 20.1) Index Regimen Class: IO + IO** 25 3.6 (2.8, 6.7) 19.7 (12.4, 33.3) Index Regimen Class: IO + TKI 52 5.4 (3.6, 8.0) 13.4 (9.6, 23.8) Index Regimen Class: TKI Only 186 6.7 (5.6, 8.5) 14.4 (11.6, 16.7) Index Regimen Class: Other 28 5.4 (2.9, 8.0) 13.9 (6.9, 26.9) *Due to small sample sizes of the index regimen 1L, log-rank test was performed between index regimen 2L and 3L subgroups. **Due to small sample sizes of IO only subgroup, log-rank test was performed among IO + IO, IO + TKI, TKI only, and other subgroups.

Treatment Patterns in Patients with Chronic Myeloid Leukemia in Chronic Phase in US Clinical Practice, with a Focus on Tyrosine Kinase Inhibitor Therapy Discontinuation

Cardiovascular Hospitalization in Patients Treated with Dasatinib or Nilotinib in Simplicity, an Observational Study of Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients in Routine Clinical Practice

Dynamics of Methylation Profiling in Response to Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia

The treatment landscape for metastatic renal cell carcinoma (mRCC) has evolved in recent years with the use of tyrosine kinase inhibitors (TKIs) and immuno-oncology (IO) therapies. This study examined patient characteristics, treatment patterns, health care resource utilization (HCRU), costs, and survival for individuals with mRCC who received either IO + IO or IO + TKI combinations as first-line (1L) regimens. This retrospective cohort study used integrated claims and clinical data from a commercial health plan to study adults with mRCC who began 1L treatment between April 1, 2018, and January 31, 2023. Patient characteristics, 1L and second-line (2L) regimens, and HCRU were described. Costs were summarized per patient per month over time. Survival time was analyzed overall and partitioned into time on 1L, treatment-free survival, and survival after 2L. Patients receiving 1L IO + IO (n = 471) or IO + TKI (n = 353) regimens generally had similar baseline characteristics although among patients with risk data, 33% of IO-IO patients versus 23% of IO-TKI patients had poor risk scores. Treatment costs were higher for IO + IO in the first 3 months but lower in subsequent time intervals compared with IO + TKI. Total mean costs per patient were $720K in US dollars (USD) for IO + IO and $834K USD for IO + TKI over the course of 3 years. Medication costs represented 80% of total costs. IO + IO patients stayed on 1L therapy for a shorter duration, but cumulative survival time at 24 months was the same (63%) for both groups. Patients receiving 1L IO + IO and IO + TKI regimens had similar baseline characteristics and comparable survival at 30 months. Although IO + IO was associated with higher treatment costs in the first 3 months, the subsequent monthly costs were lower compared with IO + TKI.

P1.16-36 Treatment Patterns Among Patients with EGFRm NSCLC Treated in the US Community Oncology Setting

SummaryWe studied 60 chronic myeloid leukaemia (CML) patients with a prior history of accelerated phase (AP) including de novo AP (n = 19) and transformation to AP (n = 4), or tyrosine kinase inhibitor (TKI) therapy failure in the chronic phase (CP, n = 37), who discontinued TKI therapy. Median interval from diagnosis with AP or TKI therapy failure to achieving a deep molecular response (DMR) was 19 months (interquartile range [IQR], 9–30 months). Median TKI treatment and DMR duration were 108 months (IQR, 72–137 months) and 59 months (IQR, 39–87 months) respectively. At a median follow‐up of 21 months (IQR, 11–36 months) after TKI discontinuation, 19 (31%) patients lost the major molecular response (MMR). The 3‐year probability of a sustained MMR was 59% (95% confidence interval [CI], [45%, 78%]). In the multivariable analyses, age at discontinuation <32 years (hazard ratio [HR] = 4.1 [1.3, 12.7], p = 0.014) and BCR::ABL1 >0.1% at 12 months on TKI therapy (reference, ≤0.1%; HR = 3.9 [1.4, 11.5], p = 0.011) were significantly associated with a higher probability of MMR loss after TKI discontinuation. CML patients with a history of AP or TKI therapy failure may achieve successful treatment‐free remission after an adequate TKI therapy duration and a sustained DMR.

Treatment Patterns and Modifications of Tyrosine Kinase Inhibitors (TKI) Therapy in Early Lines in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Real-World Analysis from a Large Commercial Claims Database in the United States (US)

Real-World Treatment Patterns, Healthcare Resource Utilization and Associated Costs Among Patients with Chronic Myeloid Leukemia in Later Lines of Therapy

The potential of immune checkpoint inhibition in many hematological malignancies such as chronic myeloid leukemia (CML) has not been characterized in detail. CML is a hematopoietic stem cell disease driven by the BCR-ABL fusion gene. Tyrosine kinase inhibitor (TKI) therapy is able to induce remissions in the majority of patients. Despite treatment responses, leukemic stem cells persist in the bone marrow (BM). Enhancing antitumor immune responses has been suggested as a potential strategy of enabling treatment discontinuation and disease control in CML. We hypothesized that the bone marrow may represent a distinct immunological milieu in CML patients. Furthermore, TKI therapy has been shown to induce immunological changes. Therefore, we evaluated the expression of immune checkpoint molecules in paired samples from BM and peripheral blood (PB) in chronic phase CML patients at diagnosis and during treatment with TKIs. In addition, we monitored changes in the BM T cell receptor (TCR) repertoire induced by TKI therapy and disease resolution. We performed multicolor flow cytometry on frozen PB and BM samples from chronic phase CML patients at diagnosis and during treatment with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib as well as healthy controls. We analyzed the expression of PD-1, CTLA-4, LAG-3, ICOS and TIM-3 on T cells and PD-L1, PD-L2, CD80 and CD86 on antigen-presenting cells and CD34+ leukemic progenitor cells. TCR repertoire was assayed by deep sequencing of the CDR3 region using the immunoSEQ assay. At diagnosis, CD8+ T cells in the bone marrow exhibited a more exhausted phenotype compared to peripheral blood as measured by PD-1 positivity (26.1 vs. 12.7%, p = 0.001). This difference was recapitulated in all T cell subsets, including effector memory (TEM), terminally differentiated (TEMRA), central memory (TCM) and naïve, with the highest PD-1 positivity in TEM and TEMRA cells. In addition, dendritic cells as well as leukemic CD34+ progenitor cells expressed higher levels of PD-L1 and CD86 in BM compared to PB at diagnosis. Interestingly, TKI therapy led to a reduction of PD-1-positive CD8+ T cells in the BM after 1 and 6 months of treatment. This was accompanied by a concomitant decrease in PD-L1 and CD86 positivity on dendritic cells. Finally, treatment with dasatinib led to a reduction in TCR repertoire diversity and increased clonality at 6 months, whereas imatinib or nilotinib did not alter the repertoire diversity. In conclusion, BM and PB seem to exhibit different immunological milieus in terms of expression of immune checkpoint molecules in CML. During TKI therapy both PD-1 and PD-L1 levels decrease, suggesting at least partial reversal of immune cell exhaustion. Treatment with the TKI dasatinib is able to drive the TCR repertoire towards a more clonal composition, which has been associated with good responses to checkpoint blockade. Thus, targeted therapies such as TKIs are able to modulate immune checkpoints and T cell activity in unexpected ways, providing a potential strategy for enhancing immunotherapies in combination treatment regimens. Citation Format: Olli Dufva, Tiina Kasanen, Mohamed El Missiry, Judith Klievink, Hanna Lähteenmäki, Satu Mustjoki. Tyrosine kinase inhibitor therapy modulates immune checkpoints and TCR repertoire diversity in chronic myeloid leukemia [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A115.

Resection Combined with TKI Therapy for Resectable Liver Metastases of Gastrointestinal Stromal Tumours: Results from Three National Centres in China

Real World Treatment Patterns in Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors in First Line in an Integrated Healthcare System

U.S. Expert Consensus on Defining Intolerance to Tyrosine Kinase Inhibitor Treatment in Chronic Phase Chronic Myeloid Leukemia (CML)

Cytogenetic and Molecular Response with First- and Second-Generation Tyrosine Kinase Inhibitor (TKI) Therapy in Simplicity: An Observational Study of Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML)

Cost Effectiveness of Tyrosine Kinase Inhibitor (TKIs) Therapy in Chronic Myelogenous Leukemia (CML) in Comparison to Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Based on the Nationwide Inpatient Sample (NIS) Database from 2002 to 2011