Tandem Autologous-Allogenic HCT Offers Long-Term Remission in Multiple Myeloma

Some patients with multiple myeloma can achieve long-term remission with tandem autologous/allogeneic hematopoietic cell transplantation (HCT), with low acute and long-term toxicities, a study published in Haematology has shown.

In a previous report, researchers at Fred Hutchinson Cancer Research Center presented initial results from 102 patients with MM treated with sequential high-dose melphalan and autologous HCT followed by 200 cGy total body irradiation with or without fludarabine 90 mg/m² and allogeneic HCT.

This retrospective analysis presents the clinical outcomes of the initial patients plus 142 additional patients, all of whom received both autologous and allogeneic HCT, with a median follow-up of 8.3 years.

Patient characteristics included median age at diagnosis 51 years; 97 (42%) had high-risk cytogenetics; 57 (25%) had high-risk disease according to International Staging System (ISS) stage III and 36 (16%) according to stage R-ISS; 91 (37%) had received more than 1 induction therapy for unresponsive disease.

Donors were 179 human leukocyte antigen (HLA) identical siblings and 65 HLA-matched unrelated donors. A total of 209 patients (86%) received tandem autologous-allogeneic upfront; 35 patients (14%) failed a previous autologous HCT before the planned autologous-allogeneic transplantation.

Primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary end points were cumulative incidences of acute graft-versus-host-disease (GVHD), chronic GVHD, nonrelapse mortality (NRM), disease response, and disease relapse.

Thirty-one patients received maintenance treatment at a median of 86 days after allogeneic transplantation. Five-year rates of OS and PFS were 54% and 31%, respectively; 10-year OS and PFS were 41% and 19%, respectively. Overall NRM at 100 days was 2%; and at 5 years, 14%.

Overall survival and PFS was shorter for patients with induction-refractory disease and those with high-risk biological features. Disease relapse occurred in 152 patients, 117 of whom received salvage treatment. Clinical response was achieved in 83 of the 117 patients with a median duration of survival after relapse of 7.8 years.

In addition, relapse rate was significantly lower in a subset of patients who became negative for minimal residual disease (MRD) by flow cytometry compared with MRD-positive patients.

These results demonstrate that long-term sustained remissions in standard and high-risk MM can be achieved with tandem autologous-allogeneic HCT. However, tandem HCT did not benefit patients with ultra-high-risk disease, and patients who experienced disease progression after autologous HCT failed to response to allogeneic HCT.

Reference

Maffini E, Storer BE, Sandmaier BM, et al. Long term follow-up of tandem autologous-allogeneic hematopoietic cell transplantation for multiple myeloma [published online September 27, 2018]. Haematologica. doi: 10.3324/haematol.2018.200253