Very Early Onset of Therapy-Related Acute Myeloid Leukemia with 11q23 Rearrangement Presenting with Unusual PET Findings after R-DA-EPOCH for Primary Mediastinal Large B-Cell Lymphoma

Background: R-DA-EPOCH is an effective regimen for PMLBCL, which permits the omission of consolidative radiotherapy in the majority of patients. Patient: We describe a 27-year-old female patient, who achieved a complete remission after treatment with six cycles of R-DA-EPOCH (up to the final level). At 6 months after the end of treatment, PET/CT revealed an unexpected, diffusely increased 18FDG uptake by the bone marrow. Simultaneously, pancytopenia with monocytosis was observed. Result: The patient was diagnosed with therapy-related myelodysplastic syndrome, which rapidly evolved into acute myeloid leukemia (t-MDS/AML) with MLL rearrangements. She achieved a complete remission after induction therapy, received an allogenic transplant and remains disease-free 2 years later. Conclusions: The extremely early onset of t-MDS/AML, together with the unexpected PET/CT findings make this case unique and highlights the need for the accurate estimation of the possible dose-dependent risk of t-MDS/AML after R-DA-EPOCH in the real-life setting in patients with PMLBCL.

Consolidative radiotherapy for metastatic urothelial bladder cancer patients without progression and with no more than three residual metastatic lesions following first line systemic therapy: A prospective randomized comparative phase II trial (BLAD RAD01/GETUG-AFU V07).

TPS4588 Background: Consolidative local treatment of the primary tumor in the treatment of metastatic malignancies has shown promising results in several types of tumors, mostly relying on the seed-and-soil theory. Furthermore, the local treatment of the residual metastases following systemic treatment is a promising approach, in part due to the high incidence of progression at prior sites of disease in patients who had initially responded to chemotherapy. To date, no prospective data exists on such consolidative approach in metastatic urothelial bladder cancer (mUBC). The phase II trial BLAD-RAD01 GETUG-AFU V07 was designed to investigate the role of local consolidative radiotherapy in patients with limited mUBC and without progression following the initial phase of first-line systemic therapy. Methods: This is a phase II, multicenter, randomized open-label and comparative study. Patients with mUBC (excluding brain and liver metastases), without progression following standard first-line systemic therapy according to RECIST v1.1, and with no more than 3 residual metastatic lesions on 18FDG-PET scanner and/or contrast-enhanced CT-scanner are eligible for the study. After the completion of systemic treatment, an estimated 130 patients will be randomized in a 1:1 ratio between consolidative local treatment (pelvic radiotherapy +/- previous transurethal resection of bladder tumor, associated with stereotactic body radiotherapy (SBRT) to the residual metastases) plus standard of care (arm B) and standard of care only (arm A). Stratification is performed based upon: the center, the ECOG performance status, the administration of immunotherapy or not, the number of residual metastatic lesions and the imaging modality for assessment of the number of residual lesions. To date, standard of care for this population is maintenance treatment with avelumab. Radiotherapy regimens consist in conventionally fractionated (64Gy in 32 fractions) or hypofractionated (55Gy in 20 fractions) irradiation of the bladder, optional pelvic nodes irradiation, and 3 to 5 fractions of 6 to 18 Gy in SBRT for metastases, depending on the location. The main objective is to detect an increase in 20-month overall survival rate following chemotherapy from 50% (based upon the JAVELIN 100 trial) to 66%; this corresponds to a hazard ratio of 0.6. A total of 83 events are necessary for 85% power to detect this difference if it is true using a one-sided logrank test at the 10% of significance. Target difference, type I and II error rates are relaxed and compatibles with recommendations for comparative phase II trials. Key secondary endpoints are progression free survival, safety and quality of life. To date, one patient has been enrolled and eight centers are open for accrual. Clinical trial information: NCT04428554.

Emerging Role of Consolidative Radiotherapy After Complete Remission Following R-CHOP Immunochemotherapy in Stage III–IV Diffuse Large B-Cell Lymphoma: A Single Institutional and Case-Matched Control Study

PurposeThe role of consolidative radiotherapy (RT) after complete-remission (CR) following rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in advanced-stage diffuse large B-cell lymphoma (DLBCL) remains unclear. We retrospectively analyzed the survival outcomes and patterns of failure with our institutional experience.Material and MethodsBetween 2009 and 2018, 206 patients with stage III-IV DLBCL achieved CR after receiving R-CHOP. Propensity-score matching was used to analyze the role of consolidative RT. The consolidative RT group (n = 34) and the R-CHOP alone group (n = 68) were matched at a 1:2 ratio. After propensity-score matching, 102 patients were analyzed.ResultsWith a median follow-up of 39.7 months, 26 patients (25.5%) showed local recurrence. Only one patient failed at the previous RT field. RT was delivered to bulky sites, head and neck lesions, testes, and bone with median dose of 30.6 Gy. The most common site of failure was head and neck lesions followed by bulky sites. The 5-year overall survival (OS), progression-free survival (PFS), and isolated-local recurrence free survival (LRFS) were 73.5, 64.0, and 79.9%. In univariate and multivariate analysis, bone marrow involvement and consolidative RT were associated with isolated LRFS (p = 0.006 and 0.032) significantly.ConclusionConsolidative RT improved isolated local control. Based on the pattern of failure, we carefully suggest to radiate on initially involved bulky sites or head and neck lesions. Further studies need to be done to find out the optimal radiation dose and selection of RT site.

Role of consolidative radiotherapy for metastatic urothelial bladder cancer patients without progression and with no more than five residual metastatic lesions following first line systemic therapy: A retrospective analysis.

454 Background: Consolidative local treatment of the primary tumor and metastases in the treatment of metastatic malignancies has shown promising results in several types of primary tumors. The aim of this study is to assess consolidative radiotherapy to the bladder and to residual metastases among metastatic urothelial bladder cancer with no progression following first line systemic therapy, hypothesizing an increase in overall survival and in progression free survival. Methods: Between January 2005 and December 2018, patients who received standard first-line chemotherapy for the treatment of metastatic urothelial bladder cancer (mUBC) were retrospectively identified through the database of four Comprehensive Cancer Centers in France. Among them, patients with no disease progression following chemotherapy and with no more than 5 residual metastases were analyzed: patients who received subsequent radiotherapy (of EQD2Gy > 50Gy) to the bladder and residual metastases were included in the consolidative group (RT group), and the other patients were included in the observation group (OBS group). PFS and OS were determined from the start of the first-line chemotherapy using the Kaplan-Meier method. To account for the delay from chemotherapy initiation to consolidative radiotherapy, a Cox model with time-dependant covariates, and a 6-month landmark analyses were performed to examine OS and PFS. Results: A total of 91 patients with at least stable disease following chemotherapy and with no more than 5 residual metastases were analyzed: 51 in the RT group and 40 in the OBS group. Metachronous metastatic disease (following definitive treatment of localized UBC) was more frequent in the OBS group (19% vs 5%, p = 0.02); the median number of metastases in the RT group vs in the OBS group was: 2 (1-9) vs 3 (1-5) (p = 0.04) at metastatic presentation, and 1 (0-5) vs 2 (0-5) (p = 0.18) after completion of chemotherapy (residual lesions), respectively. Two grade 3 toxicities (3.9%) and no grade 4 toxicity were reported in the RT group. With a median follow up of 85.9 months (95% IC [36.7; 101.6]), median OS and PFS were 21.7 months (95% IC [17.1; 29.7]) and 11.1 months (95% IC [9.9; 14.1]) for the whole cohort, respectively. In multivariable analysis: consolidative RT in comparison with observation was associated with improved OS in both the standard analysis (HR = 0.47, p = 0.015) and in the 6-month landmark analysis (HR = 0.48, p = 0.026); and with improved PFS only in the standard analysis (HR = 0.49, p = 0.007). Conclusions: Consolidative radiotherapy for mUBC patients who have not progressed after chemotherapy and with limited residual disease seems to confer both OS and PFS advantage. Prospective data in that field with addition of avelumab are needed.