An Ongoing Multinational Observational Study in Multiple Myeloma (PREAMBLE): Initial Assessment of Treatment Patterns in Patients with ≥6 Months Follow-up
Authors: Vij Ravi , Annemans Lieven , Davis Catherine , Le Trong K. , Bartlett Blake , Moreau Philippe 
Published: October 2019

Abstract
INTRODUCTION
Outcomes for patients with multiple myeloma (MM) have improved in the past decade with the use of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). There are, however, limited data on real-world effectiveness of these agents in the setting of relapsed/refractory MM (RRMM). PREAMBLE (Prospective REsearch Assessment in Multiple Myeloma: an OBservationaL Evaluation; NCT01838512) is an ongoing, prospective, multinational, observational cohort study to evaluate the real-world clinical effectiveness, healthcare resource utilization, and patient-reported outcomes associated with IMiD, PI, and IMiD+PI therapy in patients with RRMM. We present initial treatment patterns and clinical effectiveness in patients with ≥6 months of follow-up in the study.
METHODS
Patients aged ≥18 years with RRMM, ≥1 prior therapy and initiating treatment with an IMiD, PI, or IMiD+PI within 90 days prior to or 30 days after study enrollment (index therapy) were eligible. Treatment was administered according to standard clinical practice. Data were collected at baseline and every 3 (Year 1) and 6 (Years 2–3) months over 3 years or until study discontinuation. Assessment of clinical effectiveness included response rates and progression-free survival (PFS); response was based on defined criteria (e.g. European Group for Blood and Bone Marrow Transplant and International Myeloma Working Group criteria), or clinical judgment.
RESULTS
At the time of the data cut-off (8 May 2014), 274 patients were enrolled: 209 (76.3%) were still in the study, 65 (24%) had discontinued; 55 (85%) discontinuations were due to death. Results are reported for 189/274 (69%) patients (Europe n=105 [56%]; North America n=84 [44%]) with ≥6 months (median 11.1 months) follow-up; the majority (165/189; 87%) were alive at the data cut-off. Median time from diagnosis to start of index therapy was 41.0 months. Eighty-nine (49%) patients had 1 prior line of therapy (n=181); 58 patients (32%) had 2 lines of prior therapy (median 95 days between regimens). Most patients received prior regimens containing a PI (53%) or IMiD (46%); 19% received regimens containing both. Of patients receiving IMiD index therapy (n=87), 66% were from Europe and 35% were from North America; 52% and 48% of patients receiving PI index therapy (n=87) were from Europe and North America, respectively. Most patients with combination index therapy (IMiD+PI, n=15) were from North America (80%). Approximately half of patients (102/189; 54%) permanently discontinued or switched index treatment regimen, occurring after (median) 3.8 months, most often due to disease progression (20/102; 20%) or toxicity (20/102; 20%). Patients who switched (29/189; 15%) did so in (median) 21 days. The most common switch was bortezomib to lenalidomide (5/29; 17%); patients receiving lenalidomide most commonly switched to bortezomib (4/8; 50%). Around one fifth of patients (6/29; 21%) switched to a triplet regimen (IMiD+PI). Regional treatment patterns are planned for inclusion in the presentation. Median PFS was 9.0 months, 6-month PFS rate was 77%, and overall response rate was 39%. PFS and response rate by class of index regimen are provided in the table; subset analyses by line of therapy are planned for inclusion in the presentation. TableIMiD-based regimens (n=87)PI-based regimens (n=87)IMiD+PI-based regimens (n=15)PFS, median (95% CI) months9 (7, 12)11 (7, 13)7 (5, NE)6-month PFS rate, % (95% CI)79 (65, 88)76 (62, 85)69 (21, 91)Response rate, %, (95% CI)39 (29, 50)44 (33, 55)7 (0.2, 32)
NE, not estimable due to insufficient follow-up time, limited number of patients, and limited number of events among these patients.
CONCLUSIONS
In this initial assessment of patients with ≥6 months of follow up in PREAMBLE, a greater proportion of patients from Europe received an IMiD as index therapy compared with those from North America. Treatment regimens were discontinued or switched for over half of patients, predominantly due to disease progression or toxicity. Additional follow-up is needed to better understand the implications of treatment patterns observed in real-world clinical practice, and specific reasons for disease progression and toxicity in patient subgroups and regions.
Study funded by Bristol-Myers Squibb.
Professional medical writing and editorial assistance was provided by Alyson Bexfield, Caudex Medical, funded by Bristol-Myers Squibb.

Disclosures
Vij: Sanofi: Honoraria; Novartis: Honoraria; Millennium: Honoraria; Janssen: Honoraria; Array: Honoraria; Onyx: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Annemans:Bristol-Myers Squibb: Consultancy. Davis:Bristol-Myers Squibb: Employment. Le:Bristol-Myers Squibb: Employment. Bartlett:Bristol-Myers Squibb: Employment; Bristol-Myers Squibb: Equity Ownership. Moreau:BMS, Celgene, Novartis, Millenium, Janssen: Honoraria; BMS, Celgene, Novartis, Millenium, Janssen: Membership on an entity's Board of Directors or advisory committees.