Each month, the Multiple Myeloma (MM) Hub will be providing content on a different educational theme. This month the MM Hub will be focusing on patient reported outcomes (PROs) and quality of life assessments (QoL). This article will introduce PROs and QoL assessments in MM, as well as set the scene for the content that will be following in the coming weeks.
Current treatment paradigm for MM
Treatment options for patients with MM are rapidly evolving, consisting currently of; immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), histone deacetylase (HDAC) inhibitors, autologous stem cell transplant (ASCT), allogeneic stem cell transplant (allo-SCT) and monoclonal antibodies. Many other novel drugs are in clinical trials, for example, chimeric antigen receptor (CAR) T-cell therapy. Usually these drugs are used in combination, with an aim of achieving a profound response to first-line therapy. However, MM is a disease characterized by frequent relapses, with patients often becoming refractory to the drugs used. Furthermore, the use of combination therapies comes with associated toxicity, and the more lines of treatment a patient receives, the more complications and treatment-related symptoms develop. 1
Various factors will be considered by a physician when determining the correct course of treatment. Some of these include transplant eligibility, age, frailty, disease stage at diagnosis, comorbidities and the genetic profile of the disease, specific to each patient. 1Since patients develop more complications over time, the use of therapies have to be carefully considered, with health-related QoL (HRQoL) being a key factor in treatment decisions. The ability to predict response to treatment will also assist treatment decisions, as we move into an era where personalized medicine is becoming plausible. 1
Impact of drug administration on QoL
MM is predominately a disease affecting elderly patients, with a third of patients being over the age of 75 at diagnosis. 1Patient age itself does not preclude certain treatment options, however it is a consideration for determining appropriate treatment. Treatments administered in the outpatient setting or at home are sought after, as this prevents the necessity to travel to a hospital facility which can often require long journeys. Examples of these treatment options include the IMiDs, such as lenalidomide, which are orally administered. 1
Additionally, subcutaneous (SC) administration is becoming more frequently used to minimize infusion time and improve tolerability. The recent COLUMBA trial, demonstrated that SC administration of daratumumab was non-inferior to intravenous (IV) infusion. In this study, the median duration of infusion with SC daratumumab was reduced to five minutes, compared to seven hours for the first, and 4.3 hours for the second when given as an IV. Significantly, in this study, patients reported an improved experience with SC daratumumab. 2
María-Victoria Mateos | Highlights of the randomized phase III COLUMBA study
Frailty scores in MM
There is a general consensus that age alone is not a predictor of response, and that frailty should be incorporated into treatment decisions. However, there is a lack of agreement over the definition of frailty in MM. 1,3.
Frailty can include: 1
- Decline in functional capabilities due to disease-related symptoms
- Medical comorbidities such as high blood pressure, heart conditions and renal failure
- Cognitive impairment
- The use of other medications
It is important for physicians to agree on the definition of frailty, in order to make best-informed choices for each patient, to ensure QoL is maintained. This is significant since older, frail patients, may not experience a benefit from treatments which cause severe side effects, and potentially lead to early mortality. Novel treatments have the potential to circumvent some of the negative impact that frailty has on clinical outcome, though studies utilizing a universally accepted frailty index are required. Currently, different models are used, meaning results cannot be directly compared. 3
Professor Zweegmanspoke to the MM Hub about the issue of frailty in MM, which can be viewed below.