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Multicenter Study
. 2012 Jan;26(1):149-57.
doi: 10.1038/leu.2011.196. Epub 2011 Jul 29.

Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study

S K Kumar  1 , J H Lee, J J Lahuerta, G Morgan, P G Richardson, J Crowley, J Haessler, J Feather, A Hoering, P Moreau, X LeLeu, C Hulin, S K Klein, P Sonneveld, D Siegel, J Bladé, H Goldschmidt, S Jagannath, J S Miguel, R Orlowski, A Palumbo, O Sezer, S V Rajkumar, B G M Durie; International Myeloma Working Group
Collaborators, Affiliations
Multicenter Study

Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study

S K Kumar et al. Leukemia. 2012 Jan.

Erratum in

  • Leukemia. 2012 May;26(5):1153. Nari, Hareth [corrected to Nahi, Hareth]

Abstract

Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T(0)). The median age at diagnosis was 58 years, and time from diagnosis to T(0) was 3.3 years. Following T(0), 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T(0) in 94 patients (44%) including ≥ partial response in 69 (32%). The median overall survival and event-free survival from T(0) were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs.

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Figures

Figure 1
Figure 1
Figure shows the time to response at any time after time zero (T0) for the different categories of responses among 213 patients who received at least one treatment after T0.
Figure 2
Figure 2
Panel A shows the Kaplan Meier curves for event free survival (red curve, median 5 months) and overall survival (blue curve, median 9 months) from T0 all patients (n=286) enrolled on the study. Panel B shows the Kaplan Meier curves for event free survival (blue curve, median 5 months) and overall survival (red curve, median 10 months) from T0 for refractory patients (n=90).
Figure 2
Figure 2
Panel A shows the Kaplan Meier curves for event free survival (red curve, median 5 months) and overall survival (blue curve, median 9 months) from T0 all patients (n=286) enrolled on the study. Panel B shows the Kaplan Meier curves for event free survival (blue curve, median 5 months) and overall survival (red curve, median 10 months) from T0 for refractory patients (n=90).
Figure 3
Figure 3
Panel A shows the overall survival among patients who did or did not receive an autologous stem cell transplant at any time after T0. Panel B shows a similar comparison, but is landmarked at 3 months by considering only transplants done within 3 months from T0.
Figure 3
Figure 3
Panel A shows the overall survival among patients who did or did not receive an autologous stem cell transplant at any time after T0. Panel B shows a similar comparison, but is landmarked at 3 months by considering only transplants done within 3 months from T0.
Figure 4
Figure 4
Panel A shows the overall survival by ISS stage at T0. Panel B compares the overall survival following T0 among patients with with either t(4;14) or hypodiploidy, compared to the remaining patients. Panel C shows the overall survival among patients with elevated creatinine at T0, compared to the remaining patients.
Figure 4
Figure 4
Panel A shows the overall survival by ISS stage at T0. Panel B compares the overall survival following T0 among patients with with either t(4;14) or hypodiploidy, compared to the remaining patients. Panel C shows the overall survival among patients with elevated creatinine at T0, compared to the remaining patients.
Figure 4
Figure 4
Panel A shows the overall survival by ISS stage at T0. Panel B compares the overall survival following T0 among patients with with either t(4;14) or hypodiploidy, compared to the remaining patients. Panel C shows the overall survival among patients with elevated creatinine at T0, compared to the remaining patients.
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References

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