Background: Bridging therapy (BT) with systemic therapy (ST), radiation therapy (RT), or combined-modality therapy (CMT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). We report the long-term outcomes of the patients who received commercial CAR T-cell therapy with or without BT. Methods: The patients with LBCL who underwent infusion of a commercial CD19 CAR T product were eligible. The radiation was stratified as comprehensive or focal. The efficacy outcomes and toxicity were analyzed. Results: In total, 156 patients were included and, of them, 52.5% of the patients received BT. The median progression-free survival (PFS) was 0.65 years in the BT cohort compared to 1.45 years in the non-BT cohort. The median overall survival (OS) was 3.16 years in the BT cohort and was not reached in the non-BT cohort. The patients who received comprehensive radiation (versus focal) had significantly improved PFS and OS, achieving a 1-year PFS of 100% vs. 9.1% and 1-year OS of 100% vs. 45.5%. There was no difference in the severe toxicity between any of the nonbridging or BT cohorts. Conclusions: BT did not appear to compromise outcomes with respect to response rates, disease control, survival, and toxicity. The patients with limited disease treated with RT had favorable outcomes.

Primary mediastinal large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL). PMBCL comprises approximately 10% of DLBCLs, thus making it a rare variant of DLBCL. Cure rates for PMBCL with upfront regimens like DA-REPOCH exceed 90%. However, if there is a poor response to this first-line therapy, relapsed/refractory PMBCL (rrPMBCL) has limited treatment options. The historic trend is to treat rrPMBCL with salvage regimens commonly used for DLBCL followed by high-dose therapy and autologous stem cell transplant (HDT-ASCT); however, response rates to salvage therapy remain low and few patients are able to proceed to transplant. An interesting feature of PMBCL is that even though it is classified as a subtype of DLBCL, PMBCL actually shares many clinical, pathologic, and genetic features with classical Hodgkin lymphoma (cHL). For example, both frequently express program death ligand 1 and 2 (PD-L1/2), which is not seen in other mature B-cell lymphomas. The expression of PD-L1/2 in PMBCL makes PDL1 inhibitors, such as pembrolizumab, an attractive therapeutic target. Pembrolizumab is an effective and well-tolerated therapy now approved for a number of cancer types from advanced melanoma to relapsed/refractory cHL. There are now multi-institutional trials underway assessing the role of pembrolizumab in the treatment of rrPMBCL.

Background: With the advent of modern radiation treatment technologies such as intensity modulated radiation therapy (IMRT), there has been increasing interest in its use for total body irradiation (TBI) conditioning regimens for hematopoietic cell transplantation (HCT) to achieve lower doses to critical organs such as the lungs and kidneys. Although this has been reported on in early studies, long-term safety and efficacy data is limited.Methods: We performed a single institution matched-pair retrospective analysis of patients treated with IMRT TBI and standard TBI between 2010 and 2020 to provide data on long-term outcomes. Patients with hematologic malignancies, who could not tolerate standing for traditional TBI or who received prior radiation received IMRT TBI. Patients were matched based on age, diagnosis, disease status, and year of transplant, and were matched 2:1 to the standard TBI and IMRT TBI cohorts. Patient and treatment characteristics, toxicity, graft-versus-host disease (GVHD), dosimetry, and outcomes were evaluated for each cohort.Results: A total of 13 patients met inclusion criteria for the IMRT cohort, leading to 26 patients in the standard TBI cohort. There was no significant difference in relevant clinical factors between the cohorts. Reasons for using IMRT over conventional TBI included being unable to stand (n=5), prior radiation (n=5), and pediatric patient requiring anesthesia (n=3). Among living patients, median follow-up for all patients was 5.1 years in the IMRT TBI cohort and 5.5 years in the standard TBI cohort. The 5-yr estimate of OS was 68% in the IMRT TBI cohort and 60% in the standard TBI cohort (p=0.706). The 5-yr estimate of RFS was 54% in the IMRT TBI cohort and 60% in the standard TBI cohort (p=0.529). There was no clinically significant pneumonitis, nephritis, hypothyroidism, or cataracts reported in the IMRT TBI cohort. 41.7% of patients in the IMRT TBI cohort and 79.2% of patients in the standard TBI cohort experienced Grade II-IV acute GVHD (p=0.023).Conclusions: IMRT TBI appears to lead to favorable long-term outcome and dosimetry, and therefore potentially improved long-term toxicity profile compared to conventional TBI. IMRT TBI warrants further investigation as part of larger prospective trials.

Background: Radium-223 is approved for treatment of bone metastases in metastatic castration-resistant prostate cancer (mCRPC). After the ALSYMPCA trial showed overall survival benefit with the addition of radium-223 to standard of care in mCRPC in 2013, there have been numerous publications and trials using radium-223 in mCRPC. Recently, there has been interest in using radium-223 earlier in the metastatic prostate cancer timeline, in metastatic castrate-sensitive prostate cancer (mCSPC); however, currently, radium-223 in mCSPC treatment is investigational. Aim: A literature search was conducted to review the use of radium-223 in mCSPC treatment from 1980 to 2019. A review of both radium-223 articles and abstracts was performed. Search terms included metastatic prostate cancer and radium-223, mCSPC, hormone-sensitive metastatic prostate cancer, radium-223, and oligometastatic disease. The results were limited to studies involving multiple patients with mCSPC. Conclusion: There are a limited number of studies of radium-223 in mCSPC treatment and the authors report on these studies (two published studies and four ongoing trials). Trials are currently underway to assess if radium-223 could be used in mCSPC as a treatment for bone metastases and micrometastases. Future data from these trials will be informative as to the benefit of radium-223 in mCSPC treatment and may change treatment paradigms for mCSPC. This review will focus on trials assessing the role of radium 223 in mCSPC.