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ASCT for fit, older patients in Myeloma XI
A
Figure 3. Outcomes of patients in age-matched groups including inverse probability of treatment weighting. (A) Progression-free survival. (B) Overall survival. TE-ASCT (blue): patients in the transplant- eligible pathway who underwent autologous stem cell transplantation; TE-noASCT (red): patients in the transplant-eligible pathway who did not under- go autologous stem cell transplantation; TNE (yel- low): patients in the transplant-ineligible pathway; ITT: intention to treat; IPTW: inverse probability of treatment weighting adjustment.
B
the age groups. It is unknown what the local investigators set as the target harvest for each patient and it may be that the target for older patients was to collect enough stem cells for one transplant rather than to also save some for a possible subsequent transplant given that by the time of relapse the older patients would have achieved an even more advanced age.
The PFS of patients in the TE pathway aged 65-69 and those aged 70-75 was shorter than that of patients aged under 65 years. This would be expected as outcomes are known to diminish with increasing age with all myeloma therapies. There was no significant difference in OS, although the survival curves appeared to dissociate for the 70-75 age group after 3 years. To further investigate this we performed OS analysis corrected for population-level mortality risk and found no evidence of a difference in sur- vival. ASCT delivery to selected older patients was safe; there was no difference in survival at 3 months or 1 year after ASCT between age groups. Indeed, fewer serious adverse events occurred within 100 days of ASCT among
those in the oldest age group. This may be due to the small size of this age group or due to more stringent selec- tion for fitness in these older patients.
There was no significant difference in PFS or OS in this study when comparing patients of a similar age who received 140 mg/m2 melphalan (due to renal impairment or clinician choice) or 200 mg/m2 melphalan as condition- ing for ASCT. This reinforces the approach of using a dose reduction of melphalan conditioning only in these selected subsets of patients, with no apparent detriment to out- comes. One previous study suggested that there was increased toxicity with the higher dose in those aged over 70 years24 but a much larger and more recent study of the EBMT Registry database did not reveal any significant dif- ference in survival outcomes between the groups receiv- ing different doses in the overall population, but a benefit from the use of 200 mg/m2 in those with a suboptimal response.25 As in our study, far fewer patients received the 140 mg/m2 dose than the 200 mg/m2 dose in the EBMT analysis, suggesting that the lower dose was only used in
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