Autologous Stem Cell Transplantation provides additional cytoreduction following induction therapy in multiple myeloma
Shaji Kumar, M.D., Martha Q. Lacy, M.D., Angela Dispenzieri, M.D., Suzanne R. Hayman, M.D., S. Vincent Rajkumar, M.D., Steve Zeldenrust, M.D., John A Lust, M.D., Philip R. Greipp, M.D., Robert A. Kyle, M.D., Dennis
Gastineau, M.D., Morie A. Gertz. M.D., Division of Hematology, Mayo Clinic, Rochester, MN, United States, 55905.
Background
Results
· High dose therapy (HDT) and stem cell transplant has been shown to improve survival in patients with myeloma and remains the
standard of care.
· A total of 440 patients were studied; 271 (61.5%) of whom had a transplant within one year of
· However, the reported results of initial HDT in these patients reflect the combined effect of the induction therapy and the HDT.
their diagnosis and were the primary focus of this analysis.
The contribution of HDT on its own is often difficult to analyze in this group with varying degree of response to initial therapy.
·. Among the 271 patients, 140 (52%) were in the initial plateau, 99 (36%) failed to achieve a
·In this single institution retrospective study, we have analyzed the results of HDT in a group of patients with measurable disease at
PR to initial therapy and 32 (12%) were in their first relapse.
the time of HDT.
·The response rates to HDT included CR (24%), VGPR (7%), PR (52%), MR or less (17%).
The median progression free survival was 23.6 mos and the overall survival from HDT was 62
Patients and Methods
mos.
·The median progression free survival from transplant was 31.7 m (95% CI; 22.3-41.1) for
· We identified patients from our transplant database, who had measurable disease at the time of initiation of transplant as defined by a
those with a CR/VGPR , 21.3 m (17.9 ­ 24.8) for those with at least a PR and 24.7 (13.7-35.8)
serum M protein of > 1.0 g/dL, 24 hour urine M-protein > 200 mg or a bone marrow plasma cell % of > 30.
for those with less than a PR (P = 0.07)
·Details regarding the clinical outcome were obtained from the database and from patient clinical records.
·The median overall survival post HDT was similar for all three categories of response
·Chi square test was used for comparison of nominal variables and t-test for continuous variables. Kaplan Meier analysis was used for
·In a multivariate analysis, presence of cytogenetic abnormalities (RR: 2.5) and high plasma
comparing survival and Cox proportional hazards was employed to identify predictors of progression free and overall survival.
cell labeling index (> 1%) (RR: 2.4) at HDT and failure to achieve a CR or VGPR (RR: 1.7)
were prognostic for decreased progression free survival post HDT.
·Responses were defined by the EBMTR criteria, using the measurements at the time of HDT and the lowest measurement obtained.
VGPR required a 90% reduction in the serum M component with urine protein < 100 mg/24 hours.
·In a similar model, only high PCLI (RR: 2.8) and abnormal cytogenetics (RR: 2.5) at HDT
predicted for poor overall survival after transplant.
·While measurements at transplant do not correlate strictly with response to initial therapy, the aim of this study was to understand the
individual contribution of HDT in these patients. All responses are graded based on the reduction in tumor burden from pre-transplant
·Among the late transplants (more than 12 months from diagnosis) (n = 169); the responses
to post transplant. Thus some of the patients who would have been classified as having a partial response to induction and HDT may
included CR (23%), VGPR (8%), PR (61%) and MR or less (8%).
be classified as non-responders in this analysis.
·Among this group, the median PFS was 16.7 m with a CR/VGPR compared to 12.5 m with PR
and 9.2 m with less than PR
Results and Conclusion
P F S fr o m T ra n s p la n t (E a r ly T r a n s p la n t)
O S fr o m T ra n s p la n t (E a r ly T ra n s p la n t)
P rog ression F ree S u rviv al-L ate Transp la nt
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CR/V G PR
CR/V G PR
CR /V G P R
Conclusions
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PR
PR
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No P R
No P R
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·This study provides a sense of the contribution of HDT, independent of the initial therapy, by
determining responses based on the immediate pre-transplant disease measurements and the best
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values observed post transplant.
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P = 0.07
P = 0.01
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·In this group of patients with residual measurable disease after the initial therapy, HDT therapy
P = 0.6
leads to additional complete responses in nearly a quarter of the patients and a VGPR in another
0.2
0.2
0.2
7%, an outcome associated with better progressin free survival.
·These numbers will provide a historical comparison for trials evaluating novel consolidation
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100
120
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160
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therapies for myeloma.
T im e (m o n th s )
T im e (m o n th s )
Tim e (m o n th s)
Disclosures: No relevant conflicts of interest to disclose

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