An Ongoing Multinational Observational Study in Multiple Myeloma (PREAMBLE): Preliminary Report on Patient Survival
Authors: Cook Gordon , Cella David , Durie Brian , Goldschmidt Hartmut , Kuter David , Moreau Philippe , Vij Ravi , Davis Catherine , Oukessou Abderrahim , Zyczynski Teresa , Popov Sergey , Palumbo Antonio 
Published: October 2019

Abstract
Introduction: Multiple myeloma (MM) is a B-cell hematologic malignancy associated with significant disease and treatment-related morbidities. Therapies including immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have improved treatment outcomes. However, MM remains incurable and there are limited data on the effectiveness of treatment in the real world. PREAMBLE (Prospective REsearch Assessment in multiple Myeloma: an oBservationaL Evaluation; NCT01838512) is an ongoing, prospective, multinational, observational cohort study to improve understanding of the real-world clinical effectiveness of IMiDs, PIs, and combination therapy in relapsed or refractory MM (RRMM). Preliminary survival data are reported here.
Methods: Eligibility criteria include patients with RRMM aged ≥18 years who have received ≥1 prior therapy and initiate treatment with IMiD, PI, or IMiD+PI within 90 days prior to or 30 days after study enrollment. Patient data are collected at each healthcare provider visit and entered into the electronic case report forms by site staff. Data were summarized using descriptive statistics.
Results: Survival data were available for 627 treated patients (median age 68 years, 56% male; 66% EU, 34% North America). Median number of prior therapies was 2 (range 1-14). At study entry, 136 (22%) patients had refractory MM and, where International Staging System (ISS) data were available (n=370; 59%),140, 108, and 122 patients had Stage III, II, and I disease, respectively. Median time since initial diagnosis was 41 months (range 1-277). Comorbid medical conditions included vascular disorders (n=268, 43%), cardiac disorders (n=89, 14%), metabolic disorders (n=178, 28%), and musculoskeletal disorders (n=154, 25%). Most patients were receiving an IMiD (45%, n=292; lenalidomide 82%, n=238/292) or PI (47%, n=293; bortezomib 81%, n=238/293); 7% (n=42) were receiving an IMiD+PI.
At data cut-off (June 16, 2015), 420 (67%) patients were still on study; median follow-up was 13 months. Main reason for discontinuation was death (145/206; 70%), while death due to MM accounted for 52% (106/206). Median survival has not yet been reached (Figure). Since study enrollment, 12-month overall survival was 78% (95% CI 74.2, 81.7), meaning that 12-month mortality (all causes) was 22% (95% CI 18.3, 25.8), while 12-month MM-associated mortality was 17% (95% CI 13.4, 20.2); therefore, around 5% of deaths were due to non-MM-related causes. Overall death rates and deaths due to MM were similar across age groups and were slightly higher in men (Table). Death rates were independent of the number of other medical conditions, number of lines of prior therapy, and refractory vs relapsed disease status. ISS disease stage at study entry was strongly associated with rate of overall deaths and deaths due to MM, with increasing disease severity associated with higher death rates.
Analyses are under way, and will be presented, to assess the impact on mortality of comorbidities, prior lines of therapy, and patient outcomes by prior lines of therapy.
Conclusions: MM is generally considered a disease of the elderly, who often have comorbidities that confound disease pathology and treatment. Preliminary survival analysis in a real-world clinical setting indicates that the majority of deaths in this study were attributed to MM, and not to other medical conditions. These real-world data, demonstrate the need for novel therapeutics in MM, especially in relapsed or refractory disease.
Study funding: Bristol-Myers Squibb. Writing assistance provided by Kate Rees, PhD, at Caudex, and funded by Bristol-Myers Squibb.
Table 1. Death rates by baseline demographics, disease characteristics, and medical history Treated n Died due to MM n (%) Died due to any reason n (%) All patients 627 106 (17) 145 (23) Age (categorical), years <65 234 39 (17) 50 (21) 65-75 254 45 (18) 61 (24) >75 139 22 (16) 34 (25) Sex Male 350 63 (18) 88 (25) Female 277 43 (16) 57 (21) Lines of prior MM therapy 1 261 39 (15) 50 (19) 2 177 39 (22) 52 (29) 3 87 15 (17) 21 (24) >3 100 13 (13) 22 (22) Disease status at study entry Refractory MM 136 23 (17) 34 (25) Relapsed MM 488 83 (17) 111 (23) ISS stage at study entry I 122 13 (11) 16 (13) II 108 23 (21) 28 (26) III 140 31 (22) 49 (35) Unknown/missing 257 39 (15) 52 (37) Number of medical conditions 1 75 14 (19) 16 (21) 2 67 10 (15) 14 (21) 3 76 12 (16) 17 (22) 4 74 10 (14) 18 (24) 5 52 6 (12) 8 (15) >5 177 38 (22) 52 (29)

Disclosures
Cook: Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Chugai: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Jazz Pharma: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Cella:Millennium/Takeda: Consultancy; Novartis: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy. Durie:Onyx: Consultancy; Takeda: Consultancy; Johnson & Johnson: Consultancy; Celgene: Consultancy. Goldschmidt:Onyx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Chugai: Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Kuter:Bristol-Myers Squibb: Consultancy, Research Funding. Moreau:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Vij:Celgene: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Davis:Bristol-Myers Squibb: Employment. Oukessou:Bristol-Myers Squibb: Employment. Zyczynski:Bristol-Myers Squibb: Employment. Popov:Parexel: Employment; Bristol-Myers Squibb: Consultancy. Palumbo:Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Genmab A/S: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Array BioPharma: Honoraria; Sanofi-Aventis: Honoraria.