Dr Gita Thanarajasingam

An international group of experts in haematology have called for an urgent review of the way adverse events in haematological cancers are reported and managed.

In an era when targeted therapies have transformed previously incurable blood cancers to allow patients to live with disease for many years, the traditional focus on acute high grade adverse events must give way to a new focus on chronic, late and lesser grade adverse effects, according to the Lancet Haematology Commission.

“The result of treatment changes across haematological malignancies is that increasing numbers of patients are living with the challenge of managing not just their disease, but also, in some cases, continuous therapies with new, chronic toxic effects,” write the authors, led by Dr Gita Thanarajasingam, a haematologist at the Mayo Clinic, Minnesota.

They cite the example of side effects of continuous therapy such as nausea, fatigue and dizziness, which may not be regarded as  high grade by clinicians but can make patient’s quality of life miserable and contribute to poor treatment adherence and relapse.

And the growing use of immune therapies may result in autoimmune disorders that have late and persisting inflammatory adverse effects that are not picked up in short term clinical trials, they say.

“Current methods of adverse event analysis focusing solely on maximum grade tables fall short in describing delayed, chronic, or cumulative effects that can limit long-term delivery of therapy,” the authors write.

In the document published in Lancet Haematology on 12 June they outline six key areas where immediate action is needed on haematological cancer adverse events.

1. Chronic, delayed, and cumulative adverse events are not well captured, leading to incomplete and potentially inaccurate toxicity assessment.
2. Patient reported outcomes (PROs) are not a standard part of toxicity assessment and therefore tolerability of therapies for haematological malignancies from the perspective of the patient is not assessed.
3. Cumbersome reporting of the myriad of expected adverse events in the Hematopoietic stem cell transplantation  (HSCT) setting is a barrier to performing clinical trials.
4. The description and management of cumulative and late toxicities in survivors of haematological malignancy is inconsistent, inadequate, or absent.
5. Meaningful adverse events of therapy for haematological malignancies are often underreported to regulatory agencies, while reporting of uninformative adverse events might obscure true safety signals.
6. Toxicities affecting patients with haematological malignancies in routine clinical practice are difficult to capture and analyse on a large scale.

Their suggested solutions include designing postmarketing clinical trials with longer toxicity evaluation periods, boosting the use of PROs, using registry data to collect longitudinal data from haematological cancer survivors and better defining and targeting ‘real world’ toxicities that are relevant for patients.

“The success in outcomes and survival in many haematological malignancies is historically unparalleled … measures to address the broad facets of toxicity assessment must be prioritised and further developed to ultimately enhance accurate, comprehensive, patient-centred toxicity reporting that will meaningfully inform the care of patients with haematological malignancies,” they conclude.