February 4th 2024 marks World Cancer Day and the primary theme for this year is ‘closing the gap in cancer treatment’. This gap spans access to treatment and our current knowledge base on varied treatment responses across diverse patient groups. In this article, we explore how vast this gap is, understand inequality in cancer treatment/research and discuss ways we can continue to address this. Limited treatment for minorities affects all cancer types, however, we will focus on haematological malignancies (HM) as an example.
HM includes leukaemia, lymphoma and myeloma. Treatment has improved significantly in recent years and includes improved chemotherapeutic combinations, new drugs and novel modalities such as chimeric antigen receptor T-cell (CAR-T) therapy. This improvement in health outcomes, has, however, been unevenly distributed among different patient groups. These disparities include the underrepresentation of minorities in clinical trials, inequitable access to treatment and low representation in health care professionals.
Leukaemia
It was estimated that in 2023, there were 20,380 new cases of acute myeloid leukaemia in the US alone. The risk and disease biology are significantly different between ethnicities including disease-causing mutations. This manifests in a higher likelihood of death in black patients for example. Higher risk and lower overall survival are not immediately attributable to differences in tumour biology but also include access to health insurance, overall income and travel distance to treatment.
Acute lymphoblastic leukaemia (ALL)
The disease occurs predominantly in children and currently has a high survival rate due to improved chemotherapy and early detection. As before, however, these gains are not evenly distributed. Varied risk and disease burden are linked to risk subtype and gene expression. Like leukaemia, lower ALL survival is linked to non-biological factors such as income, health insurance etc. Critically, minority groups often have much more limited access to new and novel therapies like CAR-T.
Myeloma
Myeloma accounts for 10% of all HM. Uneven distribution of incidence has not yet been linked to a genetic factor, whilst timely diagnosis is impacted by social factors. Like in ALL, non-white myeloma patients are far less likely to receive new and novel therapies. In rare settings of equitable treatment access, overall survival between various ethnicities is not significantly different. Realistically, only 35.9% of black myeloma patients live in a US county with an open trial for CAR-T or bispecific antibody therapeutics.
Case study: Idecabtagene vicleucel (ide-cel)
Ide-cel was the first of the currently approved CAR-T therapies for multiple myeloma. Recently, retrospective analysis investigated racial and ethnic differences in drug safety and efficacy. The study gathered data from multiple studies and examined patient treatment responses. In addition to a general lack of diversity in clinical trials, strict inclusiveness in multiple clinical trials also present barriers in broader cancer treatment access. In fact, 75% of the patients included in the retrospective study would have been excluded from the trial which was used for submission to the FDA for the approval of ide-cel. Retrospective data showed differences in inflammatory response, with black patients more likely to develop cytokine release syndrome. Treatment response was lowest in Hispanic patients (59%) with black and white patients having response rates close to 86% This study did not discourage the use of ide-cel but crucially highlights how understudied treatment response in minority groups is.
Mitigation strategies
The FDA has strongly encouraged inclusion of diverse clinical trial participants while US legislation has been passed which requires sponsors to submit a diversity action plan for all Phase III studies or pivotal studies using new drugs. Legislature is a strong driver but there are whole-scale societal changes which need to accompany them including raising funds, awareness and government budgets to improve wider access to health insurance. Another significant barrier is the distance patients need to travel to receive in-person treatment. A simple, albeit costly intervention is to have trial sites much closer to the local communities instead of large single trial sites.
Combating inequitable access with better science
Landmark studies are only now beginning to remove the facade behind the assumption that therapeutics are effective in one population and more likely to work in another. Precision medicine is a pertinent and vital trend which aims to tailor therapies based much more closely on the recipient’s own risk and anticipated response. Steps toward more precise medicine, cannot be possible without improved means of stratifying patients, and understanding disease pathology and treatment response. Omics technologies and bespoke biomarker analyses are key but in the immediate term, it is critical to marry scientific understanding with societal intervention to ensure that new therapies reach all those who need it.
About Synexa and Scientific Strategies
Synexa is a specialised biomarker and bioanalytical services firm, established over 20 years ago. We have been supporting our clients at all stages of clinical development, from discovery to phase 3 studies. Our services cover analysis across the biological continuum, from nucleic acid, soluble biomarkers, cell and tissue. Our team of dedicated scientists, working across labs in South Africa, Europe, the UK and US, relish solving intricate and challenging biological problems.
A key extension of this; is Synexa’s Scientific Strategies Team. Synexa’s Scientific Strategies team can help de-risk your development by providing support around key biomarker and bioanalytical considerations. The dedicated team can offer standalone consulting support, providing objective, actionable solutions to your biomarker and bioanalytical challenges.
Written by Nicholas Woudberg (PhD), Scientific Director
