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Simple Summary: Approximately 50% of high-risk neuroblastomas (NB) relapse within two years after the end of treatment. The prognosis for relapsed or refractory patients is poor, and additional therapeutic options are needed. The identification of ALK somatic mutations or amplification plays an important role in the treatment of relapsed/refractory patients. The aim of our study was to evaluate the genomic status of patients with relapsed/refractory NB and to employ ALK Tyrosine Kinase Inhibitors (TKIs) in patients with targetable ALK mutations. In the era of precision medicine, ALK inhibitors may play an important role in the treatment of high-risk, ALK-mutated, NB patients. Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Patients with relapsed/refractory disease have a poor prognosis, and additional therapeutic options are needed. Mutations and amplifications in the ALK (Anaplastic Lymphoma Kinase) gene constitute a key target for treatment. Our goal, within the Italian project of PeRsonalizEdMEdicine (PREME), was to evaluate the genomic status of patients with relapsed/refractory NB and to implement targeted therapies in those with targetable mutations. From November 2018 to November 2021, we performed Whole Exome Sequencing or Targeted Gene Panel Sequencing in relapsed/refractory NB patients in order to identify druggable variants. Activating mutations of ALK were identified in 8(28.57%) of 28 relapsed/refractory NB patients. The mutation p.F1174L was found in six patients, whereas p.R1275Q was found in one and the unknown mutation p.S104R in another. Three patients died before treatment could be started, while five patients received crizotinib: two in monotherapy (one with p.F1174L and the other with p.S104R) and three (with p.F1174L variant) in combination with chemotherapy. All treated patients showed a clinical improvement, and one had complete remission after two cycles of combined treatment. The most common treatment-related toxicities were hematological. ALK inhibitors may play an important role in the treatment of ALK-mutated NB patients. [ABSTRACT FROM AUTHOR]

Because of the global coronavirus pandemic, the 2020 annual scientific meeting of the American Society of Clinical Oncology took place virtually, 29-30 May. At the meeting, results from key studies about the treatment of chronic lymphocytic leukemia (cll) were disseminated. Studies examined the efficacy and safety of ibrutinib, acalabrutinib, zanubrutinib, and venetoclax as monotherapy or in combination with novel agents for patients with treatment-naïve and relapsed or refractory cll. Our meeting report describes the foregoing studies and presents interviews with investigators and commentaries by Canadian hematologists about potential effects on Canadian practice. [ABSTRACT FROM AUTHOR]

The 2019 annual meetings of the American Society of Clinical Oncology and the European Hematology Association took place, respectively, in Chicago, Illinois, 31 May–4 June, and in Amsterdam, Netherlands, 13–16 June. At the meetings, results from key studies on the treatment of patients with relapsed or refractory multiple myeloma with high-risk cytogenetics were presented. Our meeting report describes those studies and includes interviews with investigators and commentaries by Canadian hematologists about the potential impact on Canadian practice. [ABSTRACT FROM AUTHOR]

The 2017 annual meeting of the American Society of Hematology took place 9-12 December in Atlanta, Georgia. At the meeting, results from key studies in the treatment of relapsed and refractory mantle cell lymphoma were presented. Of those studies, oral presentations focused on the efficacy and safety of therapy with Bruton tyrosine kinase (btk) inhibitors. One study presented pooled data from three trials using ibrutinib, with a median follow-up of 3.5 years. A second phase ii study presented data on the efficacy and safety of acalabrutinib, a highly selective btk inhibitor with minimal off-target activity. The final study presented early phase ib data on the efficacy and safety of zanubrutinib, a novel, highly selective btk inhibitor, in patients with non-Hodgkin lymphoma. Our meeting report describes the foregoing studies and presents interviews with investigators and commentaries by Canadian hematologists about potential effects on Canadian practice. [ABSTRACT FROM AUTHOR]

With no treatment standard having been established for relapsed and refractory follicular lymphoma, a number of therapeutic approaches are used in Canada. In patients who relapse early or who eventually become resistant to subsequent treatment, prognosis is poor, and new approaches are needed. A number of novel therapies are being examined in this setting, including monoclonal antibodies, immunoconjugates, immunomodulatory agents, and signal transduction inhibitors. With the body of evidence for those emerging therapies accumulating and the standard upfront treatment changing from rituximab and chop (cyclophosphamide-doxorubicin-vincristine-prednisone) or rituximab and CVP (cyclophosphamide-vincristine-prednisone) to bendamustine and rituximab, treatment decisions in the relapsed and refractory setting have become more complex. The choice of subsequent treatment must consider type of upfront treatment; duration of remission; and patient-related factors such as age, comorbidities, and treatment preferences. This paper summarizes the evidence for novel therapies and proposes recommendations for subsequent treatment options by remission duration after induction and maintenance. [ABSTRACT FROM AUTHOR]

Although Hodgkin lymphoma (HL) is highly curable with first-line therapy, relapses occur in approximately 10–20% of patients with early stage disease and 30–40% of patients with advanced stage disease. The standard approach for relapsed or refractory disease is salvage therapy, followed by consolidation with high dose therapy and autologous stem cell transplant (ASCT). Patients who achieve a complete response to salvage therapy prior to ASCT have better outcomes, thus recent studies have focused on incorporating newer agents in this setting. Major challenges in the management of relapsed patients remain how to choose and sequence the many salvage therapies that are currently available and how to best incorporate novel agents in the current treatment paradigms. In this article, we will summarize the most recent advances in the management of patients with recurrent HL and will mainly focus on the role of new agents approved and under investigation. Aside from brentuximab vedotin and checkpoint inhibitors, other novel agents and therapies are showing promising early results. However, at least with some of the newest targeted strategies, it is important to recognize that we are facing new challenges in terms of toxicities, which require very close monitoring and education of both the patient and treating physician. [ABSTRACT FROM AUTHOR]