Multiple myeloma and genetic testing
Patients with multiple myeloma – a type of bone marrow cancer – often have poor outcomes. Professor Guy Pratt, a clinical haematologist, explains how genetic testing can be used to aid decisions around the best treatment for patients, ultimately improving survival rates.
Multiple myeloma is a haematological cancer of plasma cells (a type of white blood cell) that arises in the bone marrow. Patients have symptoms such as pain, infections, anaemia and renal impairment. It affects over 20,000 people in the UK currently, with 5,000 new cases diagnosed each year. Late diagnosis remains a problem since patients often present with non-specific symptoms and it is relatively uncommon.
Over the last 20 years there have been significant improvements in the availability of novel treatment options. This has led to a marked improvement in outcomes. Despite this, multiple myeloma remains an ultimately fatal condition.
We are entering a new era where the results of genetic testing will increasingly be used in treatment decisions … for patients with myeloma.
Patients receive repeated treatments over years before the disease becomes resistant to treatment or patients reach a point where they cannot tolerate further treatment. Traditionally, initial treatment decisions have been based on the fitness of the patients for intensive treatment and whether severe renal failure is present. For several years it has been recognised that one in four patients with myeloma have a tumour with adverse genetic abnormalities (causing high-risk myeloma). High-risk myeloma is associated with poorer outcomes and a median survival of three years with conventional approaches.
Myeloma management has lagged behind other blood cancers in terms of genetic testing and the use of genetics in treatment decisions and discussions with patients around their outlook. The genetics of myeloma is complex and more heterogeneous (diverse) compared with other haematological cancers. However, it is known that the presence of two or more certain genetic abnormalities is associated with a worse outlook.
Myeloma UK trial 9 was the first molecularly stratified (where patients were grouped according to the molecular characteristics of their cancer) prospective trial that aimed to improve the outcome for patients with high-risk myeloma. Between 2017 and 2019, 472 patients with suspected high-risk myeloma from 39 UK NHS hospitals were screened for genetic abnormalities. Patients found to have high-risk disease genetically were offered participation in the trial.
In this trial, combinations of multiple novel agents were used during induction therapy (the first therapeutic measures taken to treat a disease) and after a stem cell transplant (where a patient receives healthy stem cells from a donor to replace damaged cells). These agents were used for the 18-month consolidation period post-transplant, followed by maintenance with two drugs. This was in contrast to current treatment regimens that use limited novel agents with a very short duration of consolidation and maintenance with just one drug.
Myeloma UK trial 9 has highlighted that outcomes for patients with high-risk genetics can be significantly improved by maintaining patients on a combination of novel agents indefinitely…
A total of 117 high-risk patients received intensive therapy with combinations of multiple drugs before, during and after the stem cell transplant. The trial demonstrated that progression-free survival at 18 months was superior for high-risk patients treated in this study compared with patients treated with current treatment strategies. The use of better-tolerated drugs helped to reduce toxicity and the regimen was well tolerated. Myeloma UK trial 9 has highlighted that outcomes for patients with high-risk genetics can be significantly improvedby maintaining patients on a combination of novel agents indefinitely and that such an approach is well tolerated with newer drugs.
Sara was 35 years old when she was diagnosed with multiple myeloma in 2018. She’d had back pain for at least a year that had worsened, limiting her mobility and requiring her to be off work. Imaging investigations showed wedge compression fractures in her spine and other bone lesions, her blood showed the presence of a myeloma protein and a bone marrow biopsy confirmed myeloma. Sara agreed to have her bone marrow screened in the Myeloma UK 9 screening trial and it showed high-risk disease.
Another feature of the Myeloma UK 9 trial is that a large percentage of patients who achieve complete remission continue in prolonged deep remission when using a combination of lenalidomide and daratumumab (drugs used to treat cancer) as a maintenance treatment.
Sara entered the trial and has tolerated treatment well including a stem cell transplant in June 2019. Four years after starting treatment her myeloma remains in a deep remission. Another feature of the Myeloma UK 9 trial is that a large percentage of patients who achieve complete remission continue in prolonged deep remission when using a combination of lenalidomide and daratumumab (drugs used to treat cancer) as a maintenance treatment.
We are entering a new era where the results of genetic testing will increasingly be used in treatment decisions as we hopefully head towards more effective personalised medicine for patients with myeloma. Indeed, examples are emerging where the genetic results of patients with myeloma have indicated high response rates to specific drugs.