The importance of autologous stem cell transplant (ASCT) in multiple myeloma treatment in the lack of novel therapies Free

Background:

Multiple Myeloma (MM) is an incurable disease; however, its management has evolved significantly in recent years with the introduction of novel therapies, but with increasing costs.

Autologous Stem Cell Transplant (ASCT) still is an option for MM patients (pts), especially in big centers with well-established routines for ASCT, and limited access to higher-cost treatment.

In Brazil, the public health system (SUS) does not offer access to monoclonal antibodies (mAb) or lenalidomide, and bortezomib has only recently become available.

Objective:

This study aims to review the clinical impact and trends of ASCT in a reference public comprehensive cancer center in Southern Brazil from 2019 to 2024.

Methods:

All MM pts who underwent ASCT from 2019 to 2024 were eligible for this retrospective cohort. Clinical data from pts chart was reviewed. Pts were analyzed by ASCT year and divided into two groups: 2019–2021 and 2022–2024, to evaluate treatment trends and clinical outcomes over time. Comparisons used the Chi-squared test or Fisher's exact test, as appropriate. The Kaplan-Meier method estimated survival probabilities, and the log-rank test for comparison. The alpha risk: 5%, with 95% confidence intervals. Statistical analysis was performed with EasyMedStat (v3.42).

Results: A total of 179pts were eligible, 105 (59%) were male, median age at ASCT was 60.6 (32.6-75) years old, characterized as ISS score at diagnosis I:21%, II:25%, III:37%, unknown(ukn):16%; Subtypes: Heavy Chain 65%, Light Chain Only 32%, Non-secretory 1%, Ukn 3%; PS-ECOG 0/1 64%, PS-ECOG 2/3 24%, ukn 12%.

There was a significant increase of 59,4% in the number of ASCT performed over the years, 2019-2022: 69pts versus 2022-2024: 110pts (p:0.02).

Pts received a median of 6 (4-38) cycles of induction chemotherapy. The group 2019-2021 received CTD (cyclophosphamide, thalidomide, dexamethasone) in 75% of cases. The group 2022-2024 received VTD (bortezomib, thalidomide, dexamethasone) in 72% of cases.

Globally, complete response (CR), very-good partial response (VGPR), and partial response (PR) were reached in 30%, 41%, and 25%, respectively.

A comparison between the groups 2019-2021 (without bortezomib) and 2022-2024 (with bortezomib) demonstrated, respectively: CR 17.9% versus 38,2%; VGPR 38,8% versus 42,7%; PR 40,3% versus 16,3% (p:0.001). Plus, the CR+VGPR rates increased from 46% (13%+33%) in 2019 to 86% (48%+38%) in 2024.

The median time from MM diagnosis to ASCT was 10.3m (4.8-70.9), decreasing over the years, from 16m (4.8-47.4) in 2019 to 8.6m (5.6-29) in 2024 (p:0.02). The conditioning regimen was melphalan, Mel200mg/m² in 71% of pts.

The response at D+100 after ASCT were CR:48%, VGPR:37%, PR:5%, Progressive Disease (PD):1%, Ukn:8%. The CR rate trended to increase, comparing group 2019-2021 CR 44,8% to group 2022-2024 CR 57,7% (p:0.347).

Median follow-up was 16.5m (0.3-77.5), with mortality 16.8% (30pts). Transplant-related mortality was 3% (5 cases). PD was the main cause of transplant non-related deaths (15pts), followed by infectious causes (6pts).

Overall survival (OS) at 12m and 24m was 91.4% (85.2-95.1) and 84.7% (76.3-90.3), respectively. There was no statistically significant difference among subgroups analyzed, except for Response Status at D+100, with OS in 2 years: CR:91.1% (79.9-96.2), VGPR: 80.8% (62.9-90.6), and PD:50% (0.6-91.0) (p<0.0001).

Conclusions: Considering that the Brazilian public health system has limited access to current treatments for MM, ASCT has been established in many scenarios, but there is a gap in reporting clinical outcomes.

This study observed that the bortezomib availability achieved deeper responses, with a significant increase in CR+VGPR pre-ASCT. Nevertheless, ASCT possibly compensated for the impact on OS for some pts in the lacking-bortezomib group, but a longer follow-up is still necessary. The OS correlated to response status at D+100, showing a clinically meaningful benefit to those pts in CR or VGPR over those with PD. Therefore, this CR/VGPR status at D+100 must be pursued.

Despite the limitations of a retrospective study, our results demonstrate literature-expected transplant-related mortality and a good rate of response and disease control. Day-care ASCT can be the next step in optimized care, with potentially equivalent survival and the best cost-effectiveness to be evaluated.