Date Published: January 29, 2019
Author(s): Huamao Mark Lin, Keith L. Davis, James A. Kaye, Katarina Luptakova, Saurabh P. Nagar, Mohamad Mohty.
Limited data are available from real-world practices in Europe describing prevailing treatment patterns and outcomes in relapsed/refractory multiple myeloma (RRMM), particularly by cytogenetic risk.
A retrospective medical record review was conducted in 200 RRMM patients in France. From first relapse, patients were assessed on second-/third-line treatments, progression-free survival (PFS), overall survival (OS), and healthcare utilization.
Fifty-five high risk and 113 standard risk patients were identified. Overall, 192 patients (96%) received second-line therapy after relapse. Lenalidomide-based regimens were most common (>50%) in second line. Hospitalization incidence in high risk patients was approximately twice that of standard risk patients. From Kaplan-Meier estimation, median (95% CI) second-line PFS was 21.4 (17.5, 25.0) months (by high versus standard risk: 10.6 [6.4, 17.0] versus 28.7 [22.1, 37.3] months). Among second-line recipients, 47.4% were deceased at data collection. Median second-line OS was 59.4 (38.8, NE) months (by high versus standard risk: 36.5 [17.4, 50.6] versus 73.6 [66.5, NE] months).
The prognostic importance of cytogenetic risk in RRMM was apparent, whereby high (versus standard) risk patients had decidedly shorter PFS and OS. Frequent hospitalizations indicated potentially high costs associated with RRMM, particularly for high risk patients. These findings may inform economic evaluations of RRMM therapies.
Multiple myeloma (MM) is a malignancy of clonal plasma cells. Worldwide, MM accounts for an estimated 0.8% (114,000) of all new cancer cases annually and 0.9% (63,000) of all cancer deaths annually [1, 2]. In Europe, a recent report suggests there were 38,928 new MM cases and 24,283 MM-attributable deaths in 2012 . Overall, MM accounts for 10% of all hematologic malignancies with median onset age of 68 years [4, 5].
A retrospective medical record review was conducted in 200 patients with RRMM in France. Patients were selected from the caseloads of 40 hematology/oncology providers practicing across France in a variety of settings: academic, university-affiliated hospitals (35%), nonacademic general hospitals (42.5%), cancer-specialized hospitals (15%), and private community hospitals and clinics (7.5%). For providers with more than 5 patients meeting the study inclusion criteria, selection of 5 patients for the review was based on randomly selected first letters of patients’ last names. All patients were aged at least 18 years at initial MM diagnosis and were first diagnosed with RRMM between January 1, 2009, and December 31, 2011. The case identification window terminated in 2011 on the basis of a median survival expectation of 3 to 6 years for RRMM patients receiving active therapy and the need in a retrospective study for an adequate potential follow-up period over which to observe relevant events. All patients were required to have a complete medical record on their treatment history related to MM, beginning with the initial MM diagnosis until death or date of last medical record entry, whichever occurred first. Patients were excluded from the study if they were diagnosed with another concurrent malignancy prior to first diagnosis of RRMM, with the exception of hematologic malignancies secondary to MM (e.g., myelodysplastic syndrome), and adequately treated nonmelanoma skin cancer or in situ neoplasm. All data collection was performed with the formal ethical approval of national competent authorities in France for the conduct of human subjects research.
As shown in Table 1, a total of 55 high risk and 113 standard risk patients were identified; risk category was unknown or unassessed for 32 patients. Mean (SD) age at first relapse was 66.3 (8.9) years and 61.5% of patients were male. Eighty-one patients (41%) received SCT (autologous SCT [n = 68] or tandem autologous SCT [n = 13]) as part of their overall first-line treatment course. Bortezomib-based systemic treatments were the most common first-line induction therapy, being observed in nearly two-thirds of all patients. In total, as shown in Figure 1, 192 patients (96%) received additional systemic therapy (i.e., second-line treatment) after first relapse. Lenalidomide-based regimens (+/- dexamethasone) were most common (>50% of patients) in second-line treatment, regardless of baseline cytogenetic risk; the median duration of these regimens was approximately 1 year over a median of 12.5 cycles. Bortezomib-based regimens (+/- dexamethasone) were next most common in second-line treatment, with a median duration of approximately 6 months over a median of 6 cycles. Among the 192 patients initiating second-line therapy, 114 (59%) also received third-line treatment; regimen compositions were more varied in the third line.
Treatment selections in the relapse setting for patients with MM depends on several parameters such as age, performance status, comorbidities, the number of prior treatment lines, available remaining treatment options, and interval since completion of last therapy. The European Medicines Association (EMA) has approved lenalidomide in combination with dexamethasone, as well as bortezomib either alone or in combination with pegylated doxorubicin, as recommended therapy for RRMM based on results of numerous trials [36–39]. Current RRMM treatment guidelines from the European Society for Medical Oncology (ESMO) acknowledge that in routine practice bortezomib is the most frequently used agent, typically in combination with dexamethasone . Among the French population reviewed here, however, the EMA-recommended second-line combination of lenalidomide/dexamethasone was, in fact, the most commonly reported regimen in second-line (53.7%), indicating that treatment selections in routine practice were consistent with guideline-based expectations.
To date, only limited data from real-world clinical settings in Europe have been generated describing current practice patterns, outcomes, and healthcare utilization in MM patients in the relapse/refractory setting. Our study found that treatment practices in real-world settings to manage relapsed MM, starting with second-line treatment, generally align with ESMO guidelines in that lenalidomide/dexamethasone was the most commonly reported second-line regimen (53.7% of patients). Furthermore, the importance of initial MM risk classification as a prognostic factor in RRMM was apparent in this retrospective review, whereby (as in previous studies) patients with high risk disease had decidedly less favorable PFS and OS than patients with standard risk. Finally, based on frequent hospitalization and emergency department visits in the relapse setting, our study demonstrates the potentially high cost burden associated with RRMM and the additional cost burden that may be incurred by patients with high risk MM as compared with standard risk. Taken together, findings from this study address important literature gaps in RRMM and may help inform future economic (e.g., cost and cost-effectiveness) evaluations of novel RRMM therapies.