Consideration of Tandem Autologous Stem Cell Transplant for Patients with Multiple Myeloma- a Large UK Single Centre Retrospective Analysis

Introduction

For patients with newly diagnosed multiple myeloma (MM), an autologous stem cell transplant (autoHSCT) remains the standard of care for patients who are fit enough. Despite advances in induction treatment, patients with adverse genetics have a poorer prognosis. In patients with MM and high risk genetics double or ‘tandem’ autoHSCT is an option and is a recommended option by BSBMTCT for patients who fail to fully respond to the first autoHSCT.

This audit examined what proportion of patients with MM are considered for a tandem transplant at our centre and to understand what factors led to proceeding to the second autograft.

Methods

We included all patients who underwent a high dose melphalan (HDM) autoHSCT at King's College Hospital between Oct 2018 and Sept 2023 for MM, or other plasma cell dyscrasias . At our centre, all patients considered for an autoHSCT are discussed at a dedicated multidisciplinary meeting and the transplant plan recorded. Patients with high risk FISH - t(4;14), t(14;16), TP53 del, or refractory to induction - are normally considered for a tandem procedure. For patients considered for a tandem we assessed the number that did not proceed to the second transplant and ascertained the reason. All patients' response to induction, R-ISS, FISH and response to their first HDM autoHSCT were examined in order to understand patient selection for a tandem.

Results

466 patients underwent HDM autoHSCT. Of those 427 were available for analysis - the remaining were not available due to a change in the Electronic Records System. Of the 427 patients who underwent a HDM autoHSCT, 39 were having a second salvage transplant at relapse and were not included in further analysis. Of the 392 patients having their first transplant, 50 (12.7%) were considered to have a tandem autoHSCT to consolidate their response; for 3 of these an allo HSCT was considered for the second transplant, for 7 patients either a second autoHSCT or a alloHSCT was considered. The induction regimens prior to transplant were most commonly VTD (38%) or D-VTD (23.2%) when available in the UK in 2022.

Overall, 30% were R-ISS 1, 38% were R-ISS 2 and 8.7% were R-ISS 3. The remaining 23.8% R-ISS was not documented. The patients who were considered for a tandem transplant were skewed towards higher R-ISS grades than the general dataset. 12% were R-ISS 1, 44% were R-ISS 2 and 28% were R-ISS 3 with 16% of patients being unable to score. 23% had TP53 del.

Of the 47 patients who had been considered for a 2^nd tandem autoHSCT, only 8 (17%) underwent the planned autoHSCT, the remaining patients did not proceed to the second transplant. Of the 8 autoHSCTs, 4 took place within 6 months, and the remaining 4 within 12 months. Of note, one patient was considered to have plasmablastic MM and underwent a BEAM autoHSCT.

Reasons for not proceeding with a second autoHSCT: 18 (38%) did not proceed as in a CR at their D100 BM, and continued to maintenance lenalidomide. An AlloHSCT was performed for 2 (4%) patients for whom a second autoHSCT was considered ; 4 (8%) patients declined to proceed with a second autograft due to difficulty in tolerating the first transplant. 3 (6%) patients had relapsed on D100 BM; and one (2%) had decline to their ECOG PS following a stroke. For 5 (11%) patients the initial MDM decision was revised and a decision made to treat the patient either with CAR-T therapy or lenalidomide maintenance. For 6 (13%) patients there was no clearly documented decision - however these patients were referred during the covid-19 pandemic.

Overall, 86% of patients were alive, 6% were recorded to have died. For the patients for whom a tandem transplant was considered 78% were still alive with 16% recorded to have died.

Mortality data for patient's undergoing HDM autoHSCT for multiple myeloma at King's College Hospital found that 5 patients of the 464 died within 100 days of the autoHSCT, resulting in a mortality rate of 1.1%.

Conclusions

In our experience a minority of patients with multiple myeloma were considered for a tandem autoHSCT (12%), and of those considered, only 17% proceeded to the planned second transplant. The most common reason for not proceeding was a deep remission on D100 BM. This reflects the improving efficacy of available induction regimens. We continue to consider that a tandem procedure has a role for a minority of patients with high risk MM however further evaluation in prospective studies would be beneficial to guide decisions as novel therapies may offer a better alternative.

Benjamin:Alimera Sciences; Servier: Research Funding; Allogene Therapeutics, Arovella Therapeutics, Bristol-Myers Squibb, Janssen, Oncopeptides, Secura Bio: Consultancy.