Author(s): S. Kumar, J. Crowley, S. K. Klein, J. J. Lahuerta, J. Lee, P. Moreau, G. Morgan, P. G. Richardson, D. S. Siegel, B. G. Durie, on behalf of the International Myeloma Working Group (IMWG)

ABSTRACT:

Background: Outcome of patients (pts) with multiple myeloma (MM) has improved with the introduction of the immunomodulatory drugs (IMiD; thalidomide, lenalidomide) and the proteasome inhibitor bortezomib (Bz). However, MM remains incurable and new therapies are needed. Improvement with upcoming therapies needs to be measured in the context of outcome with the current therapies. Moreover, the natural history of MM with the newer therapies used currently remains unclear.

Methods: We designed a multicenter, retrospective study that enrolled 270 pts with relapsed MM, from 8 sites in US, 5 in Europe and 1 in Asia. Pts were refractory to Bz, defined as no response to prior Bz-containing regimen or disease progression within 60 days of a Bz-containing regimen. Pts also had to be relapsed, refractory, intolerant, and/or ineligible, to an IMiD. Clinical and lab data from diagnosis and individual relapses were collected. The date pts satisfied the above entry criteria was defined as time zero (T₀).

Results: The median age at diagnosis was 58 years (range, 31-86) and median time from diagnosis to T₀ was 32 months (mos) and 32% had > 3 prior regimens, including a transplant (SCT) in 60%. Following T₀, 192 (71%) pts had a treatment recorded, including an SCT in 34 (13%). Various regimens were utilized after T₀ (median=1; range 0-8). The first regimen following T₀ contained Bz in 52 (27%) pts and an IMiD in 63 (33%) pts. An MR or better was seen to at least one therapy after T₀ in 87 (45%) including > PR in 65 (34%) and > VGPR in 18 (9%). The probability of achieving a PR or better was higher for younger patients, those with a VGPR or better before T₀ and those who received an SCT after T₀. The median overall survival (OS) and event free survival (EFS) were 8 mos (95% CI; 6,10) and 5 mos (95% CI; 4,5 mos) respectively.

Conclusions: This study confirms the poor outcome of pts once they relapse and become refractory to novel agents. This observational dataset will provide context for interpreting ongoing clinical trials of new drugs for MM. SCT results in higher response rates, especially in those receiving it for the first time, and should be taken into account when defining populations for studies of new drugs.