ASCT is a Safe and Effective Consolidation Treatment Option for Transplanted Elderly NDMM Patients

Autologous hematopoietic stem cell transplantation (ASCT) after induction therapy is the standard consolidation therapy for transplant-eligible patients with treatment-naive multiple myeloma (NDMM)
.

Data from two recent large phase III studies support the continuation of consolidation with ASCT in the context of current newer drug combination induction regimens; both studies excluded patients >65 years of age
.

In real-world practice, ASCT is not limited to patients under the age of 65
.

The European Bone Marrow Transplantation (EBMT) registry study shows that the number of patients >65 years old who received ASCT has increased in recent years.
During 2001-2005, 2478 patients aged 65-69 years who received ASCT accounted for 14.
1% of the total transplant patients.
In 2006 - 15.
8% increase in 2010; a similar pattern was observed in those >70 years old
.

The results showed that there was no significant difference in transplant-related mortality (TRM) among patients of different age groups, which was 1.
8% in patients aged 60-64 years, 2.
1% in patients aged 65-69 years, and 2.
4% in patients ≥70 years old
.

The Myeloma XI trial is a phase III, randomized, controlled study in transplant-eligible (TE) and transplant-ineligible (TNE) patients to explore the efficacy and toxicity of ASCT in elderly patients
.

Both TE and TNE patients in this study were randomized to receive either thalidomide- or lenalidomide-based triple induction therapy, allowing the investigators to analyze the outcomes of transplant-eligible patients across age groups, and to compare patients who received the same induction therapy.
Outcomes in patients treated with or without ASCT
.

Study Methods Myeloma XI is a phase III, open-label, parallel-group, multi-arm, adaptive trial recruiting patients with NDMM aged ≥18 years
.

This trial was designed to reflect a safe population close to the real world; therefore, exclusion criteria were limited but included prior treatment for myeloma (excluding local radiotherapy, bisphosphonates, and corticosteroids), prior or concurrent malignancy ( including myelodysplastic syndrome), grade ≥2 peripheral neuropathy, acute renal failure, and active or previous hepatitis C infection
.

Patients with TE and TNE MM were randomly assigned to triple therapy with thalidomide (cyclophosphamide, thalidomide, and dexamethasone, CTD) or triple therapy with lenalidomide (cyclophosphamide, lenalidomide) amine and dexamethasone, CRD); induction therapy for at least 4 cycles (TE) or 6 cycles (TNE) for optimal response
.

All TE patients were scheduled to undergo ASCT
.

The data cutoff date for inclusion in this study was May 31, 2019
.

Findings Outcomes of TE patients by age The median age of 2042 TE patients was 61 years (range: 28-75 years); 546 (27%) were 65-69 years, and 101 (5%) were 70 years -75 years (Table 1)
.

Elderly patients had a higher proportion of ISS stage III and poorer performance status than younger patients
.

The proportion of patients in cytogenetic risk subgroups did not differ significantly between patients in different age groups
.

Efficacy at the end of induction was similar across age groups
.

Elderly TE patients were less likely than younger patients to undergo stem cell harvesting at the end of induction
.

The percentage of patients who underwent stem cell harvesting decreased from 73.
5% for those aged <65 years to 62.
2% for those aged 65-69 years and to 57.
4% for those aged ≥70 years (Table 1)
.

Stem cell harvesting and subsequent transplantation were not performed, mainly because clinicians or patients did not consider their suitability in the elderly group (Table 1)
.

Patients of different ages achieved similar depths of response at 100 days after ASCT (Table 1), with an overall ORR of 63.
2% for patients aged <65, 65-69, and ≥70 years compared with the end of induction The ORRs were 62.
7%, 64.
5% and 63.
6%, respectively
.

Patients aged <65 years had the longest median PFS, and PFS decreased with age (Figure 1)
.

However, this result was confounded by age, as more patients in the elderly group were pretreated with melphalan at a dose of 140 mg/m2, which was associated with poorer patient PFS (Figure 1)
.

Table 1 Baseline characteristics and treatments received by age group in patients eligible for the transplant eligibility pathwayFigure 1 Outcomes in patients of different ages who underwent ASCT Differences in outcomes between ASCT and non-ASCT in age-matched elderly patients At baseline, TNE and TE- The performance status and ISS stage of patients in the non-ASCT group were higher than those in the TE-ASCT group
.

The median PFS of elderly patients with TE-ASCT was significantly better than that of elderly patients with TE-non-ASCT or TNE (Fig.
2B); the median PFS of the three groups of patients was 39.
4 months, 9.
7 months, and 16.
5 months, respectively
.

Patients with TE-ASCT were significantly improved in PFS compared with TE-non-ASCT or TNE patients (ASCT vs non-ASCT, P≤0.
0001, Figure 2D)
.

The same was observed with regard to OS: median OS was 84.
1 months, 50.
9 months, and 60.
2 months for TE-ASCT, TE-non-ASCT, and TNE patients, respectively (Fig.
2C) (ASCT vs non-ASCT, P≤0.
0001 , Figure 2E)
.

Figure 2 After adjustment for outcomes in age-matched patients, median PFS was 35.
8 months, 10.
4 months, and 16.
9 months for patients in the TE-ASCT, TE-non-ASCT, and TNE groups, respectively (Figure 3A)
.

The same benefit was observed in terms of OS after adjustment, with median OS of 79.
8 months, 57.
3 months, and 59.
5 months in the three groups of patients (ASCT vs non-ASCT, P≤0.
001) (Fig.
3B)
.

Figure 3.
Outcomes in age-matched groups of patients, including inverse probability of treatment weighted (IPTW) reported 230 serious-related adverse events (SAEs) within 100 days after ASCT: <65 years, 65-70 years, and 70-75 years of age The incidence of patients in the group was 15.
1%, 14.
6% and 7.
3%, respectively
.

Nine patients died within 100 days of ASCT: 5 were <65 years, 3 were 65-70 years, and 1 was 70-75 years
.

Forty-eight patients died within 365 days after ASCT: 34 were <65 years, 11 were 65-70 years, and 3 were 70-75 years
.

CONCLUSIONS: These findings support the use of ASCT in selected elderly patients with NDMM ≤75 years of age.
Elderly patients receiving ASCT have comparable PFS and OS to younger patients without significantly increasing patient mortality
.

References Charlotte Pawlyn , David Cairns , Tom Menzies, et al.
Autologous stem cell transplantation is safe and effective for fit older myeloma patients: exploratory results from the Myeloma XI trial.
Haematologica.
2022 Jan 1;107(1):231-242 .
Review: Quinta Typesetting: XY Execution: XY poke "read the original text", we make progress together