TPS495 Background: Radical metastasectomy and other local treatment strategies (including definitive radiotherapy, RT) can be carried out instead of systemic therapies for selected metastatic renal cell carcinoma (mRCC) patients (pts) with the aim of healing the patient even in an advanced disease stage. Recent data suggests a potential benefit from perioperative immunotherapy with immune checkpoint inhibitors (ICIs), as shown by the significant efficacy of adjuvant pembrolizumab in the M1 NED subgroup of the KEYNOTE-564 trial. Moreover, important activity of a short course of pembrolizumab has been demonstrated also in oligometastatic mRCC pts in combination with stereotactic ablative RT in the RAPPORT study. To date, no randomized trial has evaluated the concomitant use of pembrolizumab with surgery or definitive RT in mRCC compared to local therapy alone, which is the aim of our study. Methods: PE-PE study (NCT05578664) is a randomized, open-label, multicenter, phase 2 study evaluating the efficacy of pembrolizumab in delaying tumor progression in pts with oligometastatic mRCC who are candidates for radical surgery and/or definitive RT of the metastases. Eligible pts should have undergone previous nephrectomy and have maximum three metastases considered eligible for radical metastasis directed therapy (MDT; either metastasectomy or RT) and new disease must have appeared within 5 years from prior nephrectomy or metastasectomy. Pts will be randomized 2:1 to receive pembrolizumab at flat dose of 400 mg every six weeks for a total of 9 cycles (one year of therapy) and MDT from day 21 to day 42 of the cycle 1 (ARM A); or MDT alone within 42 days from randomization (ARM B). The primary endpoint is to assess the relapse free survival (RFS) defined as the length of time from randomization to the appearance of radiological progression in pts who receive pembrolizumab compared to those who do not. Secondary endpoints include: distant RFS (defined as the time from randomization to the appearance of distant metastases other those treated with surgery or RT), overall survival, and safety. Exploratory biomarkers analysis will be performed. The trial is actively recruiting. Clinical trial information: NCT05578664 .

Kidney cancer

Urothelial cancer

10.1200/jco.2024.42.4_suppl.tps495

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PROGNOSTIC VALUE OF MYOMETRIUM FREE FROM INFILTRATION IN ENDOMETRIAL ADENOCARCINOMA

International Journal of Gynecological Cancer (2004)

Roberto Maggi Francesco Spina Andrea Alberto Lissoni Federica Maggi

Myometrium

Infiltration (HVAC)

Value (mathematics)

10.1136/ijgc-00009577-200409001-00214

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Prognostic factors and outcome of reduced-intensity conditioning followed by allogeneic stem cell transplantation in patients with multiple myeloma relapsed after autografting and rescued with new drugs

Bone Marrow Transplantation (2011)

Francesca Patriarca Hermann Einsele Francesco Spina Benedetto Bruno Miriam Isola

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STUDY OF THE HEMATOLOGY MODIFICATION IN TELECOBALT THERAPY

Stefano Greco T. Papa M. Scaccianoce Francesco Spina

A statistical investigation was made on the quantitative changes of the elemerts of the peripheral blood before and after radiation treatment in 200 subjects suffering from malignant tumors treated by telecobalt-therapy. The findings showed a slight fall of the red blood cells accompanied by a considerable decrease of the hemoglobin content and by a fall of platelets, which was evident for tumors where a large volume of tissue had to be irradiated. The response of leukocytes to irradiation was different with relation to the technique employed and thus to the integral dosage and the type of distribution of the dose in the tissues. (auth)

Hematology

Radiosensitivity

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Nilotinib‐induced bone marrow CD34+/lin‐Ph+ cells early clearance in newly diagnosed CP‐Chronic Myeloid Leukemia: Final report of the PhilosoPhi34 study

European Journal Of Haematology (2021)

Ester Pungolino Mariella D’Adda Gabriella De Canal Alessandra Trojani Alessandra Perego

Chronic Myeloid Leukemia is a clonal disorder characterized by the presence of the Ph-chromosome and the BCR-ABL tyrosine-kinase (TK). Target-therapy with Imatinib has greatly improved its outcome. Deeper and faster responses are reported with the second-generation TKI Nilotinib. Sustained responses may enable TKI discontinuation. However, even in a complete molecular response, some patients experience disease recurrence possibly due to persistence of quiescent leukemic CD34+/lin-Ph+ stem cells (LSCs). Degree and mechanisms of LSCs clearance during TKI treatment are not clearly established. The PhilosoPhi34 study was designed to verify the in-vivo activity and timecourse of first-line Nilotinib therapy on BM CD34+/lin-Ph+ cells clearance. Eighty-seven CP-CML patients were enrolled. BM cells were collected and tested for Ph+ residual cells, at diagnosis, 3, 6 and 12 months of treatment. FISH analysis of unstimulated CD34+/lin- cells in CCyR patients were positive in 8/65 (12.3%), 5/71 (7%), 0/69 (0%) evaluable tests, respectively. Per-Protocol analysis response rates were as follows: CCyR 95% at 12 months, MR4.5 31% and 46% at 12 and 36 months, respectively. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin- cells was performed on 30 patients at diagnosis and after, on 79 patients at diagnosis vs 12 months of nilotinib treatment vs 10 healthy subjects. Data demonstrated some genes significantly different expressed: NFKBIA, many cell cycle genes, ABC transporters, JAK-STAT signaling pathway (JAK2). In addition, a correlation between different expression of some genes (JAK2, OLFM4, ICAM1, NFKBIA) among patients at diagnosis and their achievement of an early and deeper MR was observed.

Discontinuation

Minimal Residual Disease

10.1111/ejh.13680

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