Novel treatments such as immunotherapy or continuous oral therapy have changed the clinical picture regarding treatment of hematologic malignancies, with some therapies designed to be administered over the long term. Although overall these treatments effectively enhance survival for patients with hematologic cancers, novel therapies confer side effects that manifest differently from those of traditional therapies.
A Commission consisting of an international panel representing a broad range of academic and clinical expertise was convened to examine how adverse events with novel therapies are reported in clinical trials. Its findings were published in The Lancet Hematology.
The Commission identified target areas for evaluation: adverse event assessment in clinical trials, incorporation of patient-reported outcomes, toxicities unique to hematopoietic stem cell transplantation (HSCTs), long-term toxicity and survival, challenges in regulatory approval, and toxicity in real-world patients. Recommendations for immediate-action (1 to 5 years) and long-term (more than 5 years) solutions were provided for each.
With the potential for chronic, cumulative, and late effects, the Commission recommends longer observation study periods for dose-limiting toxicity assessments. It also suggests that information regarding adverse effects should come from multiple sources as well as be used to inform investigators and clinical practice across trials. Patient advocates can be instrumental in identifying adverse effect issues. For example, concerns about high-dose steroids within the Eastern Cooperative Oncology Group in the United States came to light through patient advocate reports. Likewise, the subjective nature of patient-reported outcomes can lead to insights on tolerability.
Specific to HSCT, the Commission recommends using data from international outcomes registries such as the Center for International Blood and Marrow Transplantation Research (CIBMTR) and the European Society for Blood and Marrow Transplantation (EBMT) to review data on which adverse events should be expected. Unexpected increases in frequency can be identified and addressed without placing an undue burden on researchers and clinicians.
The Commission’s report offers a call to action on infrastructure and health-care delivery. Adverse event reporting influences many aspects of hematologic malignancy care that are beyond clinical trials, including pre- and postmarketing vigilance, toxicity reporting in the real-world setting, and long-term survivorship. Improvements in electronic health record reporting and retrieval are key to providing universal gathering of information to support these functions.
“The success in outcomes and survival in many haematological malignancies is historically unparalleled and fueled by scientific discovery and implementation,” concluded the authors. These recommendations potentially enable adverse event reporting to keep pace with the survival enhancements provided by these new treatments.
Thanarajasingam G, Minasian LM, Baron F, et al. Beyond maximum grade: modernising the assessment and reporting of adverse events in haematological malignancies. Lancet Haematol. 2018;5(11):E563-E598.