Beyond maximum grade: modernising the assessment and reporting of adverse events in haematological malignancies

Abstract

Tremendous progress in treatment and outcomes has been achieved across the whole range of haematological malignancies in the past two decades. Although cure rates for aggressive malignancies have increased, nowhere has progress been more impactful than in the management of typically incurable forms of haematological cancer. Population-based data have shown that 5-year survival for patients with chronic myelogenous and chronic lymphocytic leukaemia, indolent B-cell lymphomas, and multiple myeloma has improved markedly. This improvement is a result of substantial changes in disease management strategies in these malignancies. Several haematological malignancies are now chronic diseases that are treated with continuously administered therapies that have unique side-effects over time. In this Commission, an international panel of clinicians, clinical investigators, methodologists, regulators, and patient advocates representing a broad range of academic and clinical cancer expertise examine adverse events in haematological malignancies. The issues pertaining to assessment of adverse events examined here are relevant to a range of malignancies and have been, to date, underexplored in the context of haematology. The aim of this Commission is to improve toxicity assessment in clinical trials in haematological malignancies by critically examining the current process of adverse event assessment, highlighting the need to incorporate patient-reported outcomes, addressing issues unique to stem-cell transplantation and survivorship, appraising challenges in regulatory approval, and evaluating toxicity in real-world patients. We have identified a range of priority issues in these areas and defined potential solutions to challenges associated with adverse event assessment in the current treatment landscape of haematological malignancies.

European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

“…The toxicity of TKIs has never been the primary endpoint of clinical studies and was not patient reported. Rather, it was evaluated based on the reports of health professionals, using severity scales designed to evaluate the acute toxicity of cytotoxic cancer chemotherapy in a clinical setting different from the setting of chronic TKI therapy [78]. Therefore, it is still difficult to provide a comparative evaluation of the frequency and the severity of toxicities [49].…”

Benefits and risks of JAK inhibition

“…The study by Porpaczy et al further underlines the importance of real-world evidence studies for assessing the longterm risks of new treatments in hematologic malignancies. 10 Studies aimed to define the risk of malignant lymphomas following JAK inhibition in real-world MPN patients are now mandatory. However, the crucial question that practicing hematologists are now facing is how to treat the next patient with myelofibrosis in whom ruxolitinib treatment would be indicated.…”

Including the patient voice in the development and implementation of patient‐reported outcomes in cancer clinical trials

“…Patients and patient advocates recognize the negative impact that a grade 1 or 2 AE, such as nausea or fatigue, can have on an individual's quality of life if it is persistent rather than transient and may suggest that PRO measures include duration as well as frequency . This is particularly relevant in the cancer patient population where extended survival may mean that treatment is given over longer periods of time.…”