Sequencing Novel Agents in Relapsed/Refractory Multiple Myeloma: Use of Bortezomib-Based Therapy After Lenalidomide + Dexamethasone.

Abstract 1853

Poster Board I-879

The optimal sequencing of novel agents in multiple myeloma (MM) is not certain. In Ontario, we had a unique opportunity to assess the efficacy of bortezomib (btz) in patients (pts) with MM who progressed after preferential treatment with lenalidomide + dexamethasone (len+dex) given via access programs/clinical trials for relapsed/refractory (rel/ref) disease. These pts all received len+dex, followed by btz-based regimens for their next relapse without any interim therapy. Between 12/2005 and 5/2009, 49 MM pts received len+dex for recurrent MM (23 in first, 20 in second, 5 in third, and 1 in fourth relapse after primary therapy). Thirty-nine pts (80%) had previously undergone autologous stem cell transplantation as part of initial therapy. Median age was 56 (range 31-77) yrs; 27 (55%) were male. The immunoglobulin subtype included IgG (21), IgA (15), IgM (1), light chain only (11) and non-secretory MM (1). ISS myeloma stage at referral consisted of stage 1 in 25 (50%), stage 2 in 18 (37%), stage 3 in 8 (16%), and not evaluable in 2 (4%) . Median β2-microglobulin level was 257 nmol/L, creatinine 77 umol/L and albumin 39 g/L. FISH cytogenetics, available in 19 pts, showed 13q del in 7, t(4;14) in 3 and p53 del in 3 pts. The median treatment duration of len+dex was 5.3 (0.5-47.5) mos; best clinical response included nCR in 3 (6%), VGPR in 3 (6%), PR in 25 (51%), MR in 6 (12%), SD in 6 (12%) and progressive disease (PD) in 6 (12%). Subsequent btz-based therapy included btz alone in 20 (41%), btz + corticosteroids (CS) in 23 (47%), btz + CS + p.o. cyclophosphamide in 4 (8%), and btz + other drug(s) in 2 (4%) of the pts. The median duration of btz-based therapy was 3.0 (0.5-17.2) mos. The best clinical response to btz-based therapy was nCR in 1 (2%), VGPR in 8 (16%), PR in 12 (25%), MR in 7 (14%), SD in 9 (18%) and PD in 12 (25%). The median follow-up from the start of btz-based therapy was 6.5 (1-29.5) mos. The median PFS and OS were 5.6 (95% CI 3.7-8.6) mos and 10.8 (95% CI 5.3-11.8) mos, while the 1-yr progression-free survival (PFS) was 20% (95% CI 9-35%) and overall survival (OS) 33% (95% CI 17-49%) mos, respectively, from the start of btz. Assessment of prognostic factors such as age at diagnosis, gender, myeloma subtype, duration from initial therapy to first relapse, previous response to len+dex, and type of btz-based therapy did not reveal a correlation with PFS or OS. However, achievement of ≥ PR with btz correlated with PFS (p=0.05) and OS (p=0.004). We conclude that treatment of sequential MM relapses with btz-based therapy after progression on len+dex: 1) produces ≥ PR in 43%; 2) results in a median PFS similar to the 6.22 mos seen with btz in less heavily pretreated pts in the APEX trial (Richardson P, et al. New Engl J Med 2005; 352:24); 3) demonstrates the effectiveness of btz even after exposure to the potent len+dex combination; 4) provides baseline information for evaluating the relative efficacy of the sequential versus combination use of novel agents in rel/ref MM.