Beyond treatment
In this section, we look beyond treatment to explore new and interesting topics related to managing MM through the lens of RWE. From clinical trial eligibility to the impact of the COVID-19 pandemic on MM management, you’ll find a diverse range of content. The implementation of RWE to better understand the MM treatment landscape and MM management is a fast-moving field. This page will be periodically updated as more information becomes available, so please check back here to review updated information.
IMPROVING THE LINK BETWEEN CLINICAL TRIAL EFFICACY AND REAL-WORLD EFFECTIVENESS
RWE can provide additional information
MM treatment options are expanding and changing the treatment landscape with novel combinations of regimens investigated in clinical trials. Favorable efficacy profiles have been demonstrated in clinical trials for multiple new standard-of-care regimens in recent years. However, treatment efficacy in a clinical trial setting may not always equate to effectiveness in a RW setting, resulting in an unmet need for many MM patients.1–3
Differing results between the clinical trial and RW settings may reflect the inclusion and exclusion criteria of clinical trials, as 40% of MM patients have been found to be ineligible for clinical trials.1–3 Therefore there is a need for additional data from trial settings that are more inclusive and representative of the general patient population.
Data from the prospective German TLN registry demonstrated that 32% of non‑transplant MM patients in routine care would not be eligible for clinical trials.1 Furthermore, trial-ineligible patients had worse first-line PFS and OS than potentially trial-eligible patients. The patient population selected specifically excluded patients with inferior prognoses, which makes data from prospective, multicenter clinical registries, such as the TLN, particularly important to complement clinical trial data.1
Similar findings have been found in patients with RRMM. In a general population‑representative database, up to 72.3% of patients receiving routine care did not meet the eligibility criteria for one of six hallmark RCTs.2 OS was different for those patients that did not meet the eligibility criteria compared to those who did meet eligibility criteria. This highlights the importance of considering RWE alongside RCT results.
Similarly, data from a cohort of the prospective Connect MM Registry, representing a RW population of NDMM patients in the US, showed that up to 40% of patients in routine care may have been ineligible to participate in a RCT.3 Moreover, RCT-ineligible patients had a lower 3-year survival rate than RCT-eligible patients (63% vs. 70%).3
“Greater efforts are required to broaden the eligibility criteria to reflect real-world clinical characteristics and narrow the gap between RCT efficacy and the observed effectiveness in real-world patients with RRMM.” 2
Conclusion
Results from clinical trials may not mirror RW patient outcomes. RW effectiveness can be impacted by exclusion of patients with certain characteristics from clinical trials. Initiatives are needed to broaden clinical trial eligibility criteria to be more representative of patient populations; otherwise, further advances in treatment will continue to be based on a small, select patient population that may not reflect the real-world MM population.
1. Knauf W et al. Ann Hematol. 2018;97:2437–2445. 2. Chari A et al. Clin Lymphoma Myeloma Leuk. 2020; 20(1):8-17.e16. 3. Shah JJ et al. Clin Lymphoma Myeloma Leuk. 2017;17(9):575-583.e2.
MM, multiple myeloma; NDMM, newly diagnosed multiple myeloma; OS, overall survival; PFS, progression-free survival; RCT, randomized controlled trial; RRMM, relapsed/refractory multiple myeloma; RW, real-world; TLN, Tumour Registry Lymphatic Neoplasms.
MANAGING PATIENTS WITH MULTIPLE MYELOMA BEYOND THE CLINICAL TRIAL SETTING: REAL-WORLD TREATMENT CHOICES
Which factors are important to patients in the RW setting?
“Efficacy does not necessarily mean the same thing to different patients.” 1
Each patient’s experience of MM is unique; therefore ‘efficacy’ may have a different meaning to different patients. The traditional definition of efficacy does not encompass many facets of the treatment experience that can impact the effectiveness which can be achieved. Safety, tolerability, feasibility, QoL and treatment satisfaction all have an impact on the outcomes that are obtainable with any given treatment regimen. To derive full benefit from a treatment, several factors that MM patients associate with the effectiveness of a treatment in a RW setting should be considered. These include symptom burden, side effects, daily activities, financial toxicity, treatment convenience/route of administration, and patient preferences. A holistic assessment should be considered to appropriately define efficacy and guide treatment for each patient, gathering input from the patient, their family, the clinical trial team, and other support teams.
Important treatment factors for RW MM patients1
Adapted from Terpos E, at al. 2021.1
Improving the link between clinical trial efficacy and real-world effectiveness:2
- Clinical trials could have broader inclusion criteria and RW studies should be defined to include data sources, minimal data requirements, and a variety of contributing centers
- Parallel collection of both clinical trial and RW data
- Standardized core set of outcomes, including more PRO and QoL data
- Incorporate assessment of PRO and QoL data routinely to allow for quicker access to drugs
- The value of PRO should be cascaded from specialized centers
- Consider parallel post-marketing trials to gather additional data to augment the clinical dataset initially available for regulatory submissions
Conclusion
Safety, tolerability, feasibility, QoL, treatment satisfaction, and efficacy, could be used in combination to determine treatment effectiveness. Such an approach may help ensure that patients with MM in the RW are represented in clinical trials so that they can access better treatments, which may ultimately improve patient QoL.
References
1. Terpos E et al. Blood Cancer Journal. 2021;11:40. 2. FDA. Framework for FDA’s Real-world evidence program. Available at: https://www.fda.gov/media/120060/download. Last accessed August 2021.
Abbreviations
MM, multiple myeloma; PRO, patient-reported outcome; QoL, quality of life; RW, real-world.