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The treatment landscape for relapsed multiple myeloma has expanded considerably in recent years, as numerous agents with new mechanisms of action have been introduced, increasing responses even in advanced disease and prolonging survival. The wealth of novel regimens comes with the challenges of balancing toxicities and aligning a regimen with the biology of the myeloma and the nature of the relapse in conjunction with patient treatment history and personal preference. Herein, we provide an overview of treatment options for both early and late relapsing disease as well as a discussion of the role of emerging immune-based therapies.

Relapsed or refractory (R/R) acute myeloid leukemia (AML) has a poor prognosis, and new therapies are a major clinical need. When mutated, FLT3 drives neoplastic cell proliferation. New drugs (i.e., tyrosine kinase inhibitors, TKIs) showed effectiveness in FLT3-AML and promise to change disease history and outcome. We evaluated the benefit conferred by TKIs in terms of survival, burden of complications and surrogate endpoint of quality of life in a retrospective cohort of 49 FLT3 positive, R/R AML patients. Patients who received TKIs were compared to those treated with conventional chemotherapy. Treatment with TKIs conferred a better OS and wea associated with a lower burden and severity of adverse events. Importantly, patients who received TKIs showed reduced time of hospitalization. In conclusion, treatment with TKI in R/R FLT3-AML was related to a better survival, less and milder AEs, and shorter hospitalization., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The last twenty years have introduced new therapeutic agents for multiple myeloma (MM); these include proteasome inhibitors (PIs), immunomodulatory drugs (IMDs) and monoclonal antibodies (mAbs). However, MM remains incurable, hence there is an unmet need for new agents for the treatment of advanced refractory disease. New agents could also be used in early lines to achieve improved, more sustained remission., Areas Covered: We review the most promising agents investigated in early-phase trials for the treatment of MM and provide an emphasis on new agents directed against well-known targets (new PIs, IMDs and anti-CD38 mAbs). Drugs that work through distinct and numerous mechanisms of action (e.g. pro-apoptotic agents and tyrosine kinase inhibitors) and innovative immunotherapeutic approaches are also described. The paper culminates with our perspective on therapeutic approaches on the horizon for this disease., Expert Opinion: IMD iberdomide and the export protein inhibitor selinexor demonstrated efficacy in heavily pretreated patients who had no other therapeutic options. We expect that immunotherapy with anti-BCMA BTEs and ADCs will revolutionize the approach to treating the early stages of the disease. Data on venetoclax in t(11;14)-positive patients may pave the way for personalized therapy. Not all new agents under early clinical evaluation will be investigated in regulatory phase III trials; one of the most important challenges is to identify those that could make a difference.

Background: Extramedullary involvement of B-cell Acute Lymphoblastic Leukemia (EM-ALL) is a rare occurrence, characterized by dismal outcome and the absence of a defined and shared therapeutic approach. In the landscape of innovative compounds, inotuzumab ozogamicin (IO) is a promising drug, whose mechanism of action relies on the killing of CD22 positive leukemic cells, through the delivery, after cell binding, of a molecule of calicheamicin., Case Presentation: We report two cases of CD22 positive relapsed EM-ALL treated with IO, obtained as compassionate use. Case 1, a 66 years old woman, affected by Philadelphia (Ph) negative B-ALL, relapsed with extramedullary involvement after 6 standard chemotherapy courses, who reached a complete metabolic response with IO treatment. Case 2, a 67 years old man with Ph positive B-ALL, initially treated with ponatinib, a third generation tyrosine-kinase inhibitor (TKI), obtaining a prolonged deep molecular remission. Nevertheless, for skin relapse during TKI treatment, the patient received local radiotherapy and, shortly after, standard chemotherapy, as multiple abdominal sites of relapse were detected too, with no response. The patient then received IO, obtained as compassionate use, with a good metabolic response., Conclusions: These two cases suggest a possible key role of IO in the setting of advanced CD22 positive ALL, and underline its potential activity also in patients with EM involvement, relapsed after or refractory to conventional chemotherapy. Despite the well known hepatotoxic effect of the compound (Sinusoid Occlusive Syndrome), neither of them had such adverse event, moreover the second patient safely underwent allogeneic bone marrow transplantation.