Lenalidomide (Revlimid®) +/− Corticosteroids in Elderly Patients with Relapsed/Refractory Multiple Myeloma.

The combination of lenalidomide (Revlimid^®) and dexamethasone (dex) is highly effective in multiple myeloma (MM) patients (pts) with relapsed/refractory disease. As MM is a disease of elderly individuals, we evaluated the outcome of pts 65 yrs and older who received Rev-based regimens through Celgene’s Expanded Access Program in Canada which commenced in 12/05; the results were compared with younger pts on this study. Our center has treated 69 pts who progressed after at least 1 prior regimen. Pts were required to have a minimum baseline neutrophil count of 1.0 x 10⁹/L and platelet count of 30 x 10⁹/L; serum creatinine level needed to be ≤220 umol/L unless a waiver was obtained. The median age was 60 yrs (35–79); 24 pts (35%) were 65 or older, 13 (19%) 70 or older and 4 (0.6%) 75 yrs or older. Fifty-two % were male; median baseline creatinine level was 91 umol/L (52–412); median β2-microglobulin was 214 nm/L (114–1420); Ig subtype was IgG in 42, IgA in 12, IgM in 1 and light chain only in 14. Prior therapy included ASCT in 59 pts (86%), thalidomide in 51 (74%), bortezomib in 21 (30%) and oral cyclophosphamide in 52 (75%); the median number of prior regimens was 2 (1–5). Rev was given with pulse dex in 44 pts (64%), prednisone in 7 (10%), dex and prednisone at different time points in 5 (7%) or as a single agent in 13 (19%); pts not receiving dex had a history of significant steroid toxicity.

RESULTS: The older and younger pt groups were well-balanced with respect to baseline characteristics, with the exception that fewer older pts had undergone prior ASCT (54% vs. 80%; p=0.04). Rev + dex was given in 54% of the older pts, compared to 69% of the younger pts; 13% vs. 9% received Rev + prednisone, 4% vs. 9% received Rev + both dex and prednisone at different time points, and 29% vs. 13% received Rev alone in older and younger pts, respectively (p= 0.37). Median follow-up is 4 mos (0.5–8). To date, the median number of cycles of Rev +/− steroids was 4 (1–8) in both age groups. Among older pts, 46% remain on Rev +/− steroids; 54% have discontinued the trial due to disease progression (21%), toxicity (12.5%), pt withdrawal (12.5%) or death (8%). In the younger age group, 49% remain on Rev therapy, while 51% have stopped due to progression (31%), toxicity (4%), withdrawal (7%) or death (9%) (p= 0.62). Table 1 summarizes toxicity seen in the 2 age groups. Using standard EBMT criteria, the partial response rate was 58%, including 1 near CR, in the older pt group, compared with 56% in younger pts (p=0.15). The actuarial progression free survival (PFS) was 43% (95% CI 26–60%) and overall survival (OS) 74% (19–65%) in older pts, compared with 43% (26–60%) and 76% (52–87%), respectively, in younger individuals.

CONCLUSION:

1. The incidence of higher grade side-effects is not increased in older pts with relapsed/refractory MM treated with Rev +/− steroids;

2. older MM pts achieve comparable response rates (approximately 60%);

3. in this preliminary analysis, the PFS and OS in older vs. younger pts are identical.