Abstract
The advent of novel immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have improved clinical outcomes of multiple myeloma (MM) in the past decade. Clinical trial data have shown combination novel therapies (IMiD+PI) can provide even further improvement. The PREAMBLE (Prospective Research Assessment in Multiple Myeloma: an Observational Evaluation) is a global study designed to evaluate clinical effectiveness, healthcare resource utilization, and patient-reported outcomes associated with novel therapies for treatment of relapsed or refractory MM (R/R MM) in the real-world daily practices in the US and Europe. We describe the study design and baseline characteristics of the first 111 patients enrolled.
This is a prospective, observational, longitudinal cohort study of adult patients with R/R MM who received at least 1 prior therapy and initiated treatment with IMiDs, PIs, or IMiDs+PIs within 90 days prior to or 30 days after enrollment. Follow-up is up to 3 yrs after consent. Patients receive standard of care treatment as determined by the treating physician. Planned enrollment is 1000 patients in North America (NA) and Europe (EU; France, Germany, Italy, and UK).
As of June 28, 2013, 111 patients from 63 sites in NA (n=64) and EU (n=47) have been enrolled. Baseline characteristics are summarized in Table 1. Cytogenetics (by FISH) was determined in 51% (n=57) of patients; of these, 16% (n=9) were high risk with del 17p (78%) as the predominant abnormality. Baseline treatment varied by region: of the patients in NA, IMiDs were used in 44% (n=28), PIs in 36% (n=23), and IMiD+PI in 20% (n=13) versus 60% (n=28), 34% (n=16), and 6% (n=3), respectively, in EU. Of the 16% high risk patients and the 25% of patients initially diagnosed at ISS stage III, none received IMiD+PI. The percentage of patients who received only 1 prior regimen at enrollment was 46% (n=26) in the IMiD group, 41% (n=16) in the PI group, and 63% (n=10) in the IMiD+PI group while the percentage of patients who received 3 or more prior regimens was 16% (n=9) in the IMiD group, 36% (n=14) in the PI group, and 6% (n=1) in the IMiD+PI group. Median time from diagnosis to enrollment for patients receiving IMiDs was 43 months, PIs was 42 months, and IMiDs+PIs was 33 months.
Baseline Characteristics by Treatment Regimen
| Treatment Regimen | |||
| IMiDs | PIs | IMiD+PI | |
| Patient Characteristics | n=56 | n=39 | n=16 |
| Median Age (yrs) (min, max) | 66 (43-87) | 69 (37-86) | 67.5 (52-87) |
| Male | 29 (52%) | 20 (51%) | 9 (56%) |
| Female | 26 (46%) | 19 (49%) | 7 (44%) |
| Missing | 1 (2%) | 0 | 0 |
| Race | |||
| White | 45 (80%) | 32 (82%) | 12 (75%) |
| Black/African American | 7 (13%) | 7 (18%) | 4 (25%) |
| Asian | 1 (2%) | 0 | 0 |
| Missing | 3 (5%) | 0 | 0 |
| Region | |||
| US | 28 (50%) | 23 (59%) | 13 (81%) |
| EU | 28 (50%) | 16 (41%) | 3 (19%) |
| Median time from initial diagnosis to enrollment (months) (min, max) | 43 (4,156) | 42 (6,128) | 33 (6,90) |
| Entry Status | |||
| Relapsed | 43 (77%) | 32 (82%) | 11 (69%) |
| Refractory | 10 (18%) | 7 (18%) | 4 (25%) |
| Missing | 3 (5%) | 0 | 1 (6%) |
| ISS Stage | |||
| I | 15 (27%) | 4 (10%) | 3 (19%) |
| II | 11 (20%) | 6 (15%) | 5 (31%) |
| III | 15 (27%) | 13 (33%) | 0 |
| Unknown | 12 (21%) | 16 (41%) | 6 (38%) |
| Missing | 3 (5%) | 0 | 2 (13%) |
| Risk Category (by FISH)1 | |||
| High | 6 (20%) | 3 (16%) | 0 |
| Intermediate | 4 (13%) | 3 (16%) | 2 (25%) |
| Standard | 20 (67%) | 13 (68%) | 6 (75%) |
| Total | 30 (100%) | 19 (100%) | 8 (100%) |
| Prior systemic therapy for MM | n=53 | n=39 | n=15 |
| Median # Prior Regimens2 | 2.0 | 2.0 | 1.0 |
| Prior regimen with IMiD | 32% | 56% | 53% |
| Prior regimen with PI | 55% | 49% | 47% |
| Prior regimen with IMiD+PI | 19% | 21% | 20% |
| 1 prior regimen | 26 (46%) | 16 (41%) | 10 (63%) |
| 2 prior regimens | 18 (32%) | 9 (23%) | 4 (25%) |
| 3+ prior regimens | 9 (16%) | 14 (36%) | 1 (6%) |
| Missing | 3 (5%) | 0 | 1 (6%) |
| Prior systemic transplantation: | |||
| No | 33 (59%) | 20 (51%) | 8 (50%) |
| Yes | 20 (36%) | 18 (46%) | 7 (44%) |
| Missing | 3 (5%) | 1 (3%) | 1 (6%) |
| Treatment Regimen | |||
| IMiDs | PIs | IMiD+PI | |
| Patient Characteristics | n=56 | n=39 | n=16 |
| Median Age (yrs) (min, max) | 66 (43-87) | 69 (37-86) | 67.5 (52-87) |
| Male | 29 (52%) | 20 (51%) | 9 (56%) |
| Female | 26 (46%) | 19 (49%) | 7 (44%) |
| Missing | 1 (2%) | 0 | 0 |
| Race | |||
| White | 45 (80%) | 32 (82%) | 12 (75%) |
| Black/African American | 7 (13%) | 7 (18%) | 4 (25%) |
| Asian | 1 (2%) | 0 | 0 |
| Missing | 3 (5%) | 0 | 0 |
| Region | |||
| US | 28 (50%) | 23 (59%) | 13 (81%) |
| EU | 28 (50%) | 16 (41%) | 3 (19%) |
| Median time from initial diagnosis to enrollment (months) (min, max) | 43 (4,156) | 42 (6,128) | 33 (6,90) |
| Entry Status | |||
| Relapsed | 43 (77%) | 32 (82%) | 11 (69%) |
| Refractory | 10 (18%) | 7 (18%) | 4 (25%) |
| Missing | 3 (5%) | 0 | 1 (6%) |
| ISS Stage | |||
| I | 15 (27%) | 4 (10%) | 3 (19%) |
| II | 11 (20%) | 6 (15%) | 5 (31%) |
| III | 15 (27%) | 13 (33%) | 0 |
| Unknown | 12 (21%) | 16 (41%) | 6 (38%) |
| Missing | 3 (5%) | 0 | 2 (13%) |
| Risk Category (by FISH)1 | |||
| High | 6 (20%) | 3 (16%) | 0 |
| Intermediate | 4 (13%) | 3 (16%) | 2 (25%) |
| Standard | 20 (67%) | 13 (68%) | 6 (75%) |
| Total | 30 (100%) | 19 (100%) | 8 (100%) |
| Prior systemic therapy for MM | n=53 | n=39 | n=15 |
| Median # Prior Regimens2 | 2.0 | 2.0 | 1.0 |
| Prior regimen with IMiD | 32% | 56% | 53% |
| Prior regimen with PI | 55% | 49% | 47% |
| Prior regimen with IMiD+PI | 19% | 21% | 20% |
| 1 prior regimen | 26 (46%) | 16 (41%) | 10 (63%) |
| 2 prior regimens | 18 (32%) | 9 (23%) | 4 (25%) |
| 3+ prior regimens | 9 (16%) | 14 (36%) | 1 (6%) |
| Missing | 3 (5%) | 0 | 1 (6%) |
| Prior systemic transplantation: | |||
| No | 33 (59%) | 20 (51%) | 8 (50%) |
| Yes | 20 (36%) | 18 (46%) | 7 (44%) |
| Missing | 3 (5%) | 1 (3%) | 1 (6%) |
Determined only in patients with adequate specimen for analysis
Prior regimens defined as having received at least one prior line of therapy for MM
PREAMBLE provides a rich data source for evaluation of clinical, economic, and humanistic outcomes in patients treated for R/R MM. Initial data suggest different treatment patterns between patients in the US and in EU. Continued follow-up and larger sample size may help identify factors associated with different treatment choices and impact on clinical effectiveness, tolerability, resource utilization, and humanistic outcomes in patients treated for R/R MM.
Vij:Celgene: Research Funding, Speakers Bureau; Onyx: Research Funding, Speakers Bureau; Millennium: Speakers Bureau; BMS: Honoraria; Lilly: Honoraria. Palumbo:Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria. Kaya:Millennium: Honoraria, Speakers Bureau. Durie:Millennium: Consultancy; Onyx: Consultancy; Celgene: Consultancy. Cella:BMS: Consultancy. Annemans:BMS: Consultancy. Su:BMS: Employment, Equity Ownership. Mukhopadhyay:BMS: Employment, Equity Ownership. Le:BMS: Employment. Petrucci:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria.
Author notes
Asterisk with author names denotes non-ASH members.
