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[Context] Adrenocorticotropin (ACTH)-secreting pituitary tumors (ACTHomas) are associated with severe comorbidities and increased mortality. Current treatments mainly focus on remission and prevention of persistent disease and recurrence. However, there are still no useful biomarkers to accurately predict the clinical outcome after surgery, long-term remission, or disease relapse., [Objectives] This work aimed to identify clinical, biochemical, and molecular markers for predicting long-term clinical outcome and remission in ACTHomas., [Methods] A retrospective multicenter study was performed with 60 ACTHomas patients diagnosed between 2004 and 2018 with at least 2 years’ follow-up. Clinical/biochemical variables were evaluated yearly. Molecular expression profile of the somatostatin/ghrelin/dopamine regulatory systems components and of key pituitary factors and proliferation markers were evaluated in tumor samples after the first surgery., [Results] Clinical variables including tumor size, time until diagnosis/first surgery, serum prolactin, and postsurgery cortisol levels were associated with tumor remission and relapsed disease. The molecular markers analyzed were distinctly expressed in ACTHomas, with some components (ie, SSTR1, CRHR1, and MKI67) showing instructive associations with recurrence and/or remission. Notably, an integrative model including selected clinical variables (tumor size/postsurgery serum cortisol), and molecular markers (SSTR1/CRHR1) can accurately predict the clinical evolution and remission of patients with ACTHomas, generating a receiver operating characteristic curve with an area under the curve of 1 (P, [Conclusion] This study demonstrates that the combination of a set of clinical and molecular biomarkers in ACTHomas is able to accurately predict the clinical evolution and remission of patients. Consequently, the postsurgery molecular profile represents a valuable tool for clinical evaluation and follow-up of patients with ACTHomas., This work was supported by the Junta de Andalucía (Nos. P20_00442, PEER-0048-2020, A-0006-2017, A-0055-2018, C-0015-2014, RC-0006-2018; postdoctoral grant DOC_01584, and BIO-0139); Ministry of Science and Innovation (Nos. PID2019-105564RB-I00 and PID2019-105201RB-I00); Instituto de Salud Carlos III, cofunded by the European Union (ERDF/ESF, “Investing in your future”; Nos. PI13/02043; PI16/00175, PI21/01012, and Sara Borrell programme CD19/00255); Spanish Ministry of Universities (predoctoral contract FPU16-05059); a GETNE2019 research grant; and CIBERobn. CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain.

Introduction. The long-term event-free survival of patients with high-risk neuroblastoma (NB) receiving intensive complex therapy according to current russian standard do not exceed 40 %. Also, there is no standard tactics in patients with primary resistant and relapsed disease, most of them die due to disease progression. While, anti-GD2 immunotherapy (IT) proved to be effective in patients with high-risk NB, in Russian Federation this method is not generally available. There are currently two pilot studies ongoing in Raisa Gorbacheva Memorial Institute aimed to evaluate the effectiveness of anti-GD2 antibodies in high-risk NB patients.Aim of the study – describing a single-center experience of anti-GD2 IT in primary high-risk NB patients and patients with primary resistant and relapsed disease.Materials and methods. A total of 20 patients received anti-GD2 antibodies, 16 of them were included into pilot trials. The median age at IT initiation was 5 (3–17) years. In 13 cases the therapy was initiated in patients with high-risk disease after auto-HSCT, in 3 cases – in patients with 1st systemic relapse of primary resistant disease after 2nd-line therapy and haplo-HSCT, in 1 case – in patient with 2nd chemosensitive relapse after haplo-HSCT. Also, 3 patients with progressive chemoresistant disease received anti-GD2 antibodies as monotherapy (n = 1) or in combination with chemotherapy (n = 2) as salvage regimen.Results. Patients receiving anti-GD2 antibodies after auto-HSCT retain response to therapy in 11 of 13 cases with a median follow-up period of 15 (6–27) months, in 2 cases there was disease progression during or immediately after IT cessation. Both patients with disease progression responded well to salvage therapy. Two of 3 haplo-HSCT recipients with prior good response to 2nd-line therapy are currently in remission 16 and 36 months past haplo-HSCT, one patient progressed 55 months after transplantation. A patient with 2nd late relapse after haplo-HSCT currently maintains remission on IT. Both patients with chemorefractory progressive disease did not respond to IT and died due to disease progression. IT was characterized by acceptable toxicity. In most cases it was complicated by Gr 1–2 fever, rash or neuropathic pain effectively controlled by supportive therapy. However, three patients had signs of neurotoxicity requiring therapy termination in one case.Conclusion. Dinutuximab beta IT is characterized by acceptable toxicity. With a median follow-up of 18 (6–59) months the majority (14 of 17) patients receiving anti-GD2 antibodies as maintenance therapy after auto- or allogeneic HSCT retain response. However, we did not observe any response in patients with progressive chemorefractory disease.

Approximately, a third of patients with diffuse large B-cell lymphoma (DLBCL) have refractory or relapsed disease after initial treatment. Despite recent regulatory approval of several new agents, including CAR-T cell therapy, polatuzumab vedotin and tafasitamab, there is still a need for additional therapies that expand the therapeutic alternatives and improve outcomes for patients with DLBCL that progresses after first line therapy.Studies of recently approved agents for relapsed DLBCL are reviewed. The relevance of CD19 as an immunotherapeutic target. The pharmacologic composition of loncastuximab tesirine and its cytotoxic payload, a pyrrolobenzodiazepine dimer. Phase I and phase 2 data for loncastuximab tesirine in non-Hodgkin lymphoma, showing the safety profile of this drug and the emerging efficacy results in DLBCL.Loncastuximab tesirine is an antiCD19 antibody drug conjugate with a novel cytotoxic payload. Early studies showed this drug is tolerable, with a safety profile that is different from other antibody drug conjugates approved for lymphoid malignancies. Efficacy data shows activity in different non-Hodgkin lymphoma entities, and a phase 2 study has been completed in DLBCL showing durable responses, including in high-risk subgroups. Loncastuximab tesirine will be an important addition to the treatment alternatives for DLBCL.

Mantle cell lymphoma (MCL) is clinically characterized by its heterogenous behavior with courses ranging from indolent cases that do not require therapy for years to highly aggressive MCL with very limited prognosis. A better understanding of the complex biology of MCL has already led to the approval of several innovative agents, expanding the landscape of MCL therapies and improving therapeutic options especially for refractory or relapsed disease. Nevertheless, to further optimize MCL treatment, early identification of individual risk profile and risk-adapted, patient-tailored choice of therapeutic strategy needs to be prospectively incorporated in clinical patient management. This review highlights recent advances in deciphering the molecular background of MCL, the definition of prognostically relevant factors and the identification of potential druggable targets and summarizes current treatment recommendations for primary and relapsed/refractory MCL including novel targeted therapies.

Background:. Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. Methods:. This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. Results:. A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%–81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. Conclusion:. Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. Clinical trial registration:. ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621

Rhabdomyosarcoma is the commonest soft tissue sarcoma in children. Clinicians need vigilance to recognize the different signs and symptoms this tumor can present with because of variable sites of origin. Diagnosis requires a safe biopsy that obtains sufficient tissue for pathologic, genetic, and biological characterization of the tumor. Treatment depends on accurate staging with imaging and surgical sampling of draining lymph nodes. A multidisciplinary team assigns patients to risk-based therapy. Patients require chemotherapy and usually a combination of complex, site-specific surgery and/or radiotherapy. Outcomes for localized rhabdomyosarcoma continue to improve but new treatments are required for metastatic and relapsed disease.

Histiocyte-rich pseudotumors (HRPT) developing postchemoradiation therapy are a florid response to treatment and reparative change. Although these are benign processes, clinically and radiologically, these may mimic recurrent/relapsed disease. We describe a case of an adult male with history of diffuse large B-cell lymphoma (DLBCL), status postchemoradiation therapy, who developed HRPT at the site of original involvement, mimicking relapse of disease on positron emission tomography/computed tomography (PET/CT) imaging. This is one of the few reported cases of posttreatment HRPT. This entity is important to point out the limitations of PET/CT imaging in patients with lymphomas and metastatic disease and stresses the importance of an excisional biopsy for determining relapse and the need for further treatment.

Mantle cell lymphoma is a rare, aggressive, and largely incurable form of non-Hodgkin lymphoma. There are a number of well-characterized prognostic features but nothing that can help guide therapy. Treatment with chemotherapy is generally effective in the short term, but relapse is inevitable and subsequent treatment is challenging. The use of Bruton tyrosine kinase inhibitors, however, has transformed practice. These agents are highly active in relapsed disease and are very well-tolerated drugs. Chemotherapy-free combinations using Bruton tyrosine kinase inhibitors look very exciting and will likely evolve to be part of frontline care in the future.

Alveolar soft part sarcoma (ASPS) is an extremely rare tumor that frequently occurs in adolescent and young adults (AYA). Survival is poor for patients with metastatic and/or relapsed disease not amenable to local control, and limited therapeutic options are available. A major barrier to cancer care in the United States AYA population is lack of access to coordinated care and appropriate therapies for those who lack insurance or who are underinsured. We report a 25-year-old unemployed, uninsured, single mother who presented with a 12.8 × 21 cm soft tissue thigh mass with heterogeneous avidity, max standardized uptake value of 9, with metastatic disease to the ipsilateral inguinal lymph nodes and to the bilateral lungs. After local control of the primary mass was obtained, a recently developed, comprehensive drug replacement program (DRP) was used to gain access to nivolumab, and after frank progression was noted, ipilimumab was added every 6 weeks. No biomarkers associated with response to immunotherapy were identified. After four cycles, a complete response was observed and patient remains disease free 36 months after beginning dual immunotherapy treatment. We obtained immunotherapy agents through a DRP and describe the development and the utility of this program in the community setting. Our report highlights both first documented sustained complete response to sequenced immunotherapy in an AYA with ASPS as well as a comprehensive DRP, which enabled access to therapy for our patient.

BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade tumor. Little is known about best treatment of primary and relapsed disease (RD). METHODS Treatment and outcome of 40 patients with DFSP prospectively registered within the CWS-96 and -2002P trials and the registry SoTiSaR (1996-2016) were analysed. RESULTS Median age was 8 years (range, 0.64-17.77). Fluorescence in situ hybridization analysis to detect COL1A1-PDGFB fusion genes was positive in 86% (12/14) of evaluated patients. Primary resection was performed in all patients. Patients had IRS group I (n = 28), II (n = 9), and III (n = 2); not available (n = 1). To achieve complete remission (CR), a secondary resection was performed in 18 patients resulting in microscopically complete (R0, n = 34/40) and microscopically incomplete (R1, n = 5/40) resection. All patients achieved CR. The 5-year event-free survival (EFS) and overall survival was 86% (±12; CI, 95%) and 100% (±0; CI, 95%), respectively. R0 resection/IRS I was significantly favorable for the 5-year EFS. Local relapse occurred after a median time of 1.1 years (range, 0.04-5.1) in 15% (6/40) after CR. All patients with RD underwent resection and achieved CR. Three patients had fibrosarcomatous DFSP, two were alive after R0 resection. CONCLUSION Complete surgical resection is mandatory to prevent relapse of DFSP.

Introduction/Background* The direct influence of irradiation on cervical cancer can be realized by brachytherapy (BT). We have developed methodic of dynamic dose fractionation of brachytherapy, which determined the relevance of this investigation. The aim of this study is efficacy improvement of combined treatment of cervical cancer patients, by application of high dose-rate brachytherapy (HDR) by the method of dynamic dose fractionation as a first step of preoperative course of radiochemotherapy. Methodology There were enrolled 54 cervical cancer patients with primary stages IB – IIA (T1b-2aNxM0). All the patients were divided into 2 groups. BT was performed by device «MultiSource», and external beam radiation therapy (EBRT) – by «Clinac 600C», with chemomodification agent cisplatin 40 mg/m2 weekly. Group 1 included 34 patients, whose treatment was started with two sessions of BT (step 1) – the first one with single dose of 7 Gy, the second one – of 5 Gy, and then EBRT (20 Gy) up to the total dose of 32/23 Gy (step 2). Group 2 included 20 patients, whose treatment was started with EBRT (20 Gy) – step 1, with sequential two sessions of BT with each single dose of 5 Gy (step 2), up to the total dose of 30/22.5 Gy. The follow-up period was 3-26 months, mean – 17.2 months. Result(s)* The effectiveness of dynamic dose fractionation HDR-BT was proved by complete tumor regression (pathomorphosis grade IV) in 35.3% of 34 patients: 50.0% of stage IB patients and 36.4% – stage IIA. In group 2, there was detected only partial tumor regression (pathomorphosis of grade II-III) in all the patients. The relapsed disease was detected in 1 (6.7%) patient of Group 2 at follow-up before 1 year. Conclusion* Dynamic dose fractionation HDR-brachytherapy, as 1st step of preoperative chemo-irradiation, allows to reach the total tumor regression, which enable further ablastic surgery and relapse-free follow-up.

Primary mediastinal (thymic) large B-cell lymphoma (PMBL) is a subtype of uncommon aggressive large B-cell lymphomas primarily occurring in mediastinum although rare cases with non-thymic type of PMBL have been reported. Typical PMBL has characteristic clinical, morphological, and immunophenotypic features which the pathologists use as diagnostic paradigm in routine practice. However, the diagnosis can be occasionally challenging due to the overlapping clinicopathologic features with other lymphomas, among which are nodular sclerosis classic Hodgkin lymphoma, systemic diffuse large B-cell lymphoma (DLBCL) involving mediastinum, and B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma (gray zone lymphoma). Recent depictions of the characteristic genetic/ molecular aberrations and unique gene expression profiling in PMBL have provided a robust tool to significantly improve the diagnostic accuracy. In addition, the progresses in understanding the pathogenesis of PMBL have paved the way discovering novel therapeutic agents for patients with refractory/relapsed disease.

Recent advances in the treatment of follicular lymphoma (FL) have provided insight into molecular and biological influences on pathogenesis and prognosis. Additionally, numerous available treatment strategies for both newly diagnosed and relapsed disease require thoughtful consideration of patient selection to avoid the burden of overtreatment and toxicities. This review provides a broad overview on our approach to managing patients with low grade FL.

The treatment of myeloma is rapidly evolving. This article reviews the current diagnostic criteria, risk stratification, and approach to treatment of multiple myeloma. Treatment approach for both newly diagnosed and relapsed disease are discussed.

Lymphoblastic lymphoma (LBL) is the second most common type of Non-Hodgkin Lymphoma (NHL) in childhood and adolescence, accounting for 25-35% of all cases. The majority, 70-80%, is of T-lymphoblastic origin while 20-25% arise from B lymphoblasts. With current therapy, the event-free and overall survivals for paediatric LBL patients now exceeds 80%. Therapy, especially in T-LBL with large mediastinal tumours, is challenging, with both significant morbidity and late sequela. An additional challenge is the dismal prognosis of patients with refractory or relapsed disease. This review article will focus on the growing knowledge of the pathogenesis and biology of LBL, recent advances and challenges in the therapy of LBL, and ongoing and future efforts and opportunities in optimizing therapy and developing novel targeted treatment approaches.

Background Children with progressive (PD) or relapsed disease (RD) of pleuropulmonary blastoma (PPB) type II/III are known to have a very poor outcome. Methods A retrospective review of children registered in national and European databases and trials (2000-2018) with diagnosis of PPB type II/III and PD or RD was performed. Results A total of 35 patients with PPB were analysed: patients with PD (n = 9) and RD (n = 26). Patients experienced PD at the median age of 3.9 years [range, 0.5-17.8] despite surgery, chemotherapy (CHT, n = 9) and radiotherapy (RT, n = 1) with a median time to progression of 0.58 years [range, 0.02-1.27] from diagnosis. All of them died. Patients suffered from RD at the median age of 4.3 years [1.7-15.1], median delay to relapse 1.03 years [range, 0.03-2.95]. RD occurred locally (n = 12), combined (n = 1) and in metastatic sites (n = 13): central nervous system (n = 11) and unspecified site (n = 2). Patients were treated with salvage CHT (n = 20), surgery (n = 10) ± RT (n = 10). After a median follow-up of 4.2 years [range, 2.1-14.6], a second complete remission (CR) was achieved in nine out of 26 patients. Patients were alive in the second CR (n = 6), in the third CR (n = 1), in partial remission (n = 2) and lost of follow-up (n = 1). Five-year event-free survival (EFS) and overall survival (OS) for patients with RD were both 37% (±19, CI 95%). Local therapy (surgery, RT) had a favourable impact on OS (p = 0.03 and 0.02, respectively). Conclusions Cure of patients with RD of PPB type II/III with multimodal treatment is possible but rare. Progressive PPB is fatal and patients need new treatment options.

Osteosarcoma is the most common bone tumor in children and young adults. Metastatic and relapsed disease confer poor prognosis, and there have been no improvements in outcomes for several decades. The disease’s biological complexity, lack of drugs developed specifically for osteosarcoma, imperfect pre-clinical models, and limits of existing clinical trial designs have contributed to lack of progress. The Children’s Oncology Group Bone Tumor Committee established the New Agents for Osteosarcoma Task Force to identify and prioritize agents for inclusion in clinical trials. The group identified multi-targeted tyrosine kinase inhibitors, immunotherapies targeting B7-H3, CD47-SIRPα inhibitors, telaglenastat, and epigenetic modifiers as the top agents of interest. Only multi-targeted tyrosine kinase inhibitors met all criteria for front-line evaluation and have already been incorporated into an upcoming phase III study concept. The task force will continue to reassess identified agents of interest as new data becomes available and evaluate novel agents using this method.

Simple Summary Cervical cancer represents one of the main leading causes of cancer-related mortality in women worldwide. In contrast to patients with early-stage disease, those with advanced, recurrent, or metastatic cervical cancer have a poor prognosis and new treatment strategies are needed. Immunotherapy has recently modified the natural course of different tumors, such as melanoma and lung cancer. The aim of this review is to evaluate the possible role of immune checkpoint inhibitors in cervical cancer treatment. Abstract Human papillomavirus (HPV) infection is the recognized cause of almost all cervical cancers. Despite the reduction in incidence due to a wide use of screening programs and a specific vaccine, the prognosis of cervical cancer remains poor, especially for late-stage and relapsed disease. Considering the elevated rates of PD-L1 expression in up to 80% of cervical cancers, a strong rationale supports the use of immunotherapy to restore the immune response against tumor. The aim of this review is to analyze the possible role of immune checkpoint inhibitors in cervical cancer treatment, with a particular focus on the rationale and on the results of phase I and II clinical trials. An overview of ongoing phase III studies with possible future areas of development is also provided.

OBJECTIVE. The purpose of this article was to evaluate the DWI features of autoimmune pancreatitis (AIP) at baseline, under treatment, and at relapse, and to assess the diagnostic accuracy of the ADC for determining disease activity. MATERIALS AND METHODS. This retrospective study was approved by the institutional review board. Sixty-two patients with AIP (48 at initial attack and 14 at relapse) underwent MRI with DWI (b = 0 and 800 s/mm2) at 3 T before receiving corticosteroid therapy (CST) and during follow-up. Seventeen patients had disease relapse during follow-up, whereas the others remained clinically stable. Forty age- and sex-matched patients without pancreatic disease served as the control group. RESULTS. The ADC value of AIP at baseline was significantly lower than that for a disease-free pancreas (0.99 ± 0.12 vs 1.26 ± 0.10 × 10-3 mm2/s, p < .001). Under CST, the ADC value increased gradually at the short-term and long-term follow-up (1.16 ± 0.12 and 1.23 ± 0.12 × 10-3 mm2/s, respectively, both p < .001). At relapse, the ADC had a relative decrease (1.11 ± 0.20 × 10-3 mm2/s) but was significantly higher compared with the initial attack (p = .003). The AUC of ADC serum IgG4 level at ROC analysis for baseline versus clinically stable AIP was 0.867 and 0.700, the AUC for clinically active AIP versus clinically stable AIP was 0.762 and 0.686, and the AUC for relapsed AIP versus clinically stable AIP was 0.648 and 0.669. CONCLUSION. DWI reflected the dynamic change of AIP under CST, and the ADC value for DWI outperformed the serum IgG4 value for determining disease activity. However, relapsed disease showed less diffusion restriction, and the ADC value was less accurate for predicting relapse.

Despite improvements in effective therapy, multiple myeloma remains incurable, and virtually all patients will face relapsed disease at some point after diagnosis. The prognosis for relapsed myeloma after developing resistance to anti-CD38 monoclonal antibodies, proteasome inhibitors, immunomodulatory agents, and autologous stem cell transplantation has been poor; however, the development of immune effector cell therapy with chimeric antigen receptor (CAR) T cells may dramatically improve the outlook for patients, although none of these therapies are approved for MM to date. Herein, we review the development and history of CAR T-cell therapy for multiple myeloma, mechanisms of resistance, and strategies to improve outcomes with CAR T therapy.

There has been extraordinary progress in the field of targeted therapy for myeloid malignancies in the last few years, especially due to the approval of various agents that can be used as monotherapy or in combination as first-line treatment or when facing a refractory or relapsed disease. Many successful trials have been conducted recently, and a consistent body of work about the efficacy of novel molecules is now available. In this review, we sought to explain how enasidenib and ivosidenib have changed the face of myeloid neoplasm treatment through isocitrate dehydrogenase inhibition and to summarize the trials results that have led to the current commercial indications for the two molecules.

Kelly Valla, PharmD, BCOP, of Winship Cancer Institute of Emory University, discusses takeaways from the session on relapsed T-cell lymphoma led by Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, at the 2020 SOHO Annual Meeting.

Background Rhabdomyosarcoma (RMS) of the female genitourinary tract (FGU-RMS) located at the vagina or uterus is one of the most favorable RMS sites. Little is known about treatment and outcome in infants and relapsed disease (RD). Methods Characteristics, treatment, and outcome of 71 children with FGU-RMS registered within five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry (1981-2019) were evaluated. Results FGU-RMS was diagnosed in 67 patients with localized disease (LD) at a median age of 2.89 years (0.09-18.08). Multimodal treatment consisted of chemotherapy (CHT) (n = 66), secondary surgery (n = 32), and radiotherapy (n = 11). Age at diagnosis ≤12 months was the only significant negative prognostic factor influencing the event-free survival (EFS). Ten-year EFS and overall survival (OS) for infants ≤12 months were 50% and 81%, respectively. In contrast, children with LD >1 year and ≤10 years had a 10-year EFS and OS of 78% and 94% (P = .038), and >10 years of 82% and 88%, respectively (P = .53). Metastatic disease was observed in four patients of which three are alive. RD occurred in five of 12 infants ≤1 year and 10/55 children at a median of 1.38 years (0.53-2.97) after initial diagnosis. Treatment of patients with RD consisted of multimodal treatment (n = 13) or resection only (n = 2). Nine patients (60%) were alive in clinical remission at a median of 7.02 years (1.23-16.72) after diagnosis of RD. Conclusion Infants with FGU-RMS have a higher relapse rate than older children with FGU-RMS, but prognosis is fair.

Bispecific antibody (BiTE) and dual-affinity retargeting (DART) therapies currently represent a novel therapeutic treatment modality for patients with acute leukemias. The first and to date only Food and Drug Administration (FDA)-approved BiTE is blinatumomab (Blincyto®), a bispecific T-cell engager that brings CD3+ T cells in proximity with CD19+ blasts. In addition to its usage for relapsed disease, blinatumomab also carries FDA approval for the treatment of minimal residual disease (MRD), a novel indication for drug approval. There are multiple other bispecific antibodies in early phase clinical trials to treat other hematologic malignancies; however, data at this time are limited. In the context of hematopoietic cell transplant (HCT), BiTE therapy has two potential roles. Treatment could occur prior to transplant to eradicate MRD, thus allowing patients to enter transplant in an MRD-negative state. However, the optimal method to eliminate MRD is unclear and whether converting an MRD-positive patient to an MRD-negative state will improve overall survival after allogeneic HCT remains unproven. Alternatively, BiTE therapy could be used in the post-transplant setting, either for overt relapsed disease or for re-emergence of MRD. Both strategies hold potential benefits; yet, data supporting their usage in these roles to date are limited. Similar opportunities may emerge if and when DART therapies earn FDA approval. Herein, the author will describe the various BiTE and DART constructs currently in development, as well as the clinical data available to date regarding their efficacy. In addition, the data supporting their usage in HCT will be discussed, along with future directions and challenges.

OBJECTIVES: To evaluate the results of radiotherapy (RT) for follicular lymphoma (FL) under different management scenarios. METHODS: We retrospectively assessed consecutive patients with FL who had undergone irradiation between 2010 and 2018. All patients had biopsy-proven FL and were positron emission tomography-staged, although some (35.3%) were reassessed with computed tomography after treatment alone. Rituximab was only available to FL patients after 2016. RESULTS: Thirty-four patients were selected, with a mean age at diagnosis of 61.6 years (34–89 years). The median follow-up duration was 49.4 months. Most patients were female (58.8%) and showed good performance on the Eastern Cooperative Oncology Group (ECOG) scale (ECOG 0-55.9%). The mean overall survival (OS) and progression-free survival were 48.7 and 33.6 months, respectively, with four deaths reported. OS rates at 2 and 3 years were 94.1% and 91.2%, respectively. Four patients showed transformation into aggressive lymphomas and underwent rituximab-based systemic treatment. Transformation-free survival was 47.8 months, and all patients with transformed disease were alive at assessment. Five patients had in-field relapse, all of them also relapsed elsewhere, and the mean relapse-free survival time was 40.3 months. No median end points were reached on assessment. CONCLUSION: FL is an indolent disease. Our findings show good outcomes for patients treated with radiation, with a low transformation rate and excellent management of relapsed disease. RT is an important part of these results.

Outcome after failure of initial therapy in younger adult patients with acute myeloid leukaemia (AML) is highly variable. Cytogenetics, length of first remission (CR1) before relapse, and allogeneic transplantation are known prognostic factors, but the contribution of leukaemic genotype is less clear, particularly in resistant disease. Of 5,651 younger adult patients entered into UK MRC/NCRI AML trials between 1988 and 2014 with available FLT3ITD and NPM1 genotype, 326 (6%) had resistant disease and 2338 (41 %) relapsed after achieving CR1. Overall survival (OS) was significantly higher in relapsed compared to resistant disease (p = 0·03). Independent favourable prognostic factors for OS in resistant disease included lower blast cell percentage after two courses of induction therapy (p = 0.0006) and NPM1 mutant (NPM1MUT) (p = 0.04). In relapsed disease, longer CR1 was a favourable independent factor for attainment of CR2 (p