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ASCT for fit, older patients in Myeloma XI
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Patients who received a melphalan dose and stem cell return (% of all patients in age group), n (%)
Patients response after- ASCT (% of all patients who received a melphalan dose and stem cell return), n (%)
Complete response
Very good partial response
Partial response
Minimal response
Progressive disease
Unable to assess
Death up to and including 100 days after ASCT Not available
1366 (66.9)
297 (21.7) 798 (58.4) 201 (14.7) 4 (0.3)
26 (1.9) 10 (0.7) 9 (0.7) 21 (1.5)
990 (70.9)
225 (22.7) 579 (58.5) 135 (13.6) 4 (0.4)
19 (1.9) 8 (0.8) 5 (0.5) 15 (1.5)
321 (58.9)
62 (19.3) 186 (57.9) 60 (18.7) 0 (0.0) 4 (1.2) 0 (0.0) 3 (0.9) 6 (1.9)
55 (54.5)
10 (18.2) 33 (60.0) 6 (10.9) 0 (0.0) 3 (5.5) 2 (3.6) 1 (1.8) 0 (0.0)
# data available for 860 of 2,042 (42.1%) patients (580 of 1,396 [41.5%] patients aged <65 years,233 of 545 [42.8%] patients 65-69 years and 47 of 101 [46.5%] patients 70-75 years). The percentages given are of those with available data.*data available for 1,364 of the 1,423 patients who underwent stem cell harvest (991 of 1,026 patients aged <65 years,320 of 339 patients aged 65-69 years, 53 of 55 patients aged 70-75 years). The percentages given are of those with data available. TE: transplant-eligible; CTD: cyclophosphamide, thalidomide and dexamethasone; CRD: cyclophosphamide, lenalidomide and dexamethasone; ASCT: autologous stem cell transplantation..
ASCT were compared. Patients of different ages achieved a similar depth of response at 100 days after ASCT (Table 1) with an improvement in response compared to the end of induction seen in 863 of 1,366 (63.2%) patients overall (62.7% of those aged <65, 64.5% of those aged 65-69 and 63.6% of those aged over 70).
The median PFS was longest for patients aged under 65 and fell with increasing age (Figure 1). The median PFS was 50.8 months (95% CI: 46.3-54.9) for those aged <65 years, 40.0 months (95% CI: 36.3-46.0) for those aged 65-69 and 34.4 months (95% CI: 27.5-46.4) for those aged 70-75 years. The PFS for patients aged 65-69 years was shorter than that of patients aged under 65 (HR=1.26, P=0.003). Patients aged 70 years or over had a shorter PFS than the <65-year age group (HR=1.57, P=0.009), but not significantly shorter than that of the 65-69 age group (HR=1.24, P=0.229).
The median OS was 95.5 months (95% CI: 89.8-not reached) for those aged <65 years, 91.9 months (95% CI: 82.3-not reached) for those aged 65-69 and 76.0 months (95% CI: 58.7-not reached) for those aged 70-75 years. There was no significant difference in the OS between any of the age groups (65-69 vs. <65: HR=1.09, P=0.484; >70 vs. <65: HR=1.59, P=0.051; 70-75 vs. 65-69, HR=1.47, P=0.127). The 5-year OS was 75.5% (95% CI: 72.6%- 78.3%) for those aged <65 years, 72.7% (95% CI: 67.3%- 78.1%) for those aged 65-69 and 65.0% (95% CI: 49.5%- 80.5%) for those aged 70-75 with some evidence of disso- ciation of the survival curve for the 70-75 age group after 3 years. There was no strong evidence of a difference in OS outcome when accounting for population-level mortality risk (excess mortality hazard-rate ratio [EHR] for OS 65-69 vs. <65: EHR=0.95, P=0.736; 70-75 vs. <65: EHR=1.33, P=0.368) (Online Supplementary Figures S2 and S3, Online Supplementary Table S2). There were also no differences in the percentages of patients who were reported as having commenced second-line therapy at the time of data cut-off (<65: 43.7%, 65-69: 49.5% and 70-75: 41.8%). However, there were notable differences in the proportions of patients whose second-line therapy included a second ASCT (23.8%, 9.4% and 8.7%, respectively).
Survival outcomes were explored stratified by melphalan dose (Online Supplementary Figure S4). Taking the whole TE population, the 140 mg/m2 dose of melphalan appeared to be associated with a shorter PFS compared to the 200 mg/m2 dose (HR=1.31, P=0.012), with no difference in OS (HR=1.29, P=0.086) (Online Supplementary Figure S4A). However, this result was confounded by age as there were more patients who received 140 mg/m2 in the older age
group which was associated with inferior PFS (Figure 1). When examined within each of the age groups there was no difference between outcome for patients who received 140 mg/m2 in comparison to those who received 200 mg/m2: age <65: PFS HR=1.20, P=0.289; OS HR=1.35, P=0.189 (Online Supplementary Figure S4B); age 65-69: PFS HR=1.18, P=0.344; OS HR=0.97, P=0.905 (Online Supplementary Figure S4C); and age >70: PFS HR=1.35, P=0.442; OS HR=1.42, P=0.522 (Online Supplementary Figure S4D).
Transplant-related morbidity and mortality were exam- ined by comparing serious adverse events reported within 100 days of ASCT and deaths occurring within 100 days or 365 days in the different age groups. There were 230 seri- ous adverse events reported within 100 days of ASCT: 172 events in 149 patients in the age group <65 years old (15.1% of patients), 54 events in 47 patients in the 65-69 age group (14.6%) and four events in four patients in the 70-75 age group (7.3%). Nine patients died within 100 days of ASCT: five aged <65 (0.5%), three aged 65-69 (0.9%) and one aged >70 (1.8%). Forty-eight patients died within 365 days of ASCT: 34 who were <65 years old (3.4%), 11 who were 65-69 (3.4%) and three who were 70-75 years old (5.5%). These data suggest that there is not a significant increase in mortality or morbidity after ASCT in older patients.
Outcomes in an age-matched group of older patients comparing transplantation to no transplantation
Analysis of the patients in the TE pathway undergoing transplantation by age does not address the question of whether, at older ages, ASCT continues to be associated with better outcomes than those of patients of an equiva- lent age not undergoing ASCT. In order to answer this ques- tion, an age-matched group of patients was identified as described above and shown in Figure 2A. At baseline, patients in both the TNE and TE-noASCT groups had high- er performance status and ISS stage than patients in the TE- ASCT group (Table 2). Response at the end of induction therapy was deeper in the patients in the TE-ASCT group than in the other two groups.
Older patients undergoing ASCT (TE-ASCT) had a longer median PFS than that of age-matched patients not undergo- ing ASCT, whether TE-noASCT or TNE (Figure 2B). The median PFS for the TE-ASCT group was 39.4 months com- pared to 9.7 months for the TE-noASCT group and 16.5 months for the TNE group. Comparing those patients who underwent ASCT (TE-ASCT) to those who did not (TE-
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