The long-term results from the phase 3 GMMG ReLApsE trial have demonstrated that adding salvage high-dose chemotherapy (sHDCT) plus autologous stem cell transplantation (ASCT) to lenalidomide and dexamethasone treatment does not provide significant survival benefits for patients with relapsed/refractory multiple myeloma.
Key Survival Outcomes
After a median follow-up of 99 months, the study revealed a median overall survival of 67.1 months in the transplant arm compared to 62.7 months in the continuous lenalidomide/dexamethasone control arm (HR, 0.89; 95% CI, 0.66-1.20; P = .44). Progression-free survival showed similarly comparable results between the arms, with 20.5 months in the transplant group versus 19.3 months in the control group (HR, 0.98; P = .9).
Study Design and Patient Population
The multicenter trial enrolled 282 patients aged 75 years and older with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy. The study was conducted across 16 German sites, with 139 patients randomized to the transplant arm and 138 to the control arm.
Patients in the transplant arm received:
- Reinduction with lenalidomide (25 mg, days 1-21)
- Dexamethasone (40 mg weekly) in 4-week cycles
- sHDCT with melphalan (200 mg/m2)
- ASCT with minimum 2 x 106 CD34-positive cells/kg
- Lenalidomide maintenance (10 mg daily)
The control group received continuous lenalidomide/dexamethasone treatment.
Patient Characteristics and Treatment History
The study population was predominantly male (57-61%) with most patients having:
- WHO performance status of 0 (69-76%)
- ISS stage I disease (60-63%)
- Normal lactate dehydrogenase levels (83%)
- Single prior line of treatment (94%)
Previous therapies included bortezomib (77%), thalidomide (18-22%), and lenalidomide (9-13%).
Treatment Challenges and Safety
Notable challenges emerged during the study, with 29% of patients in the transplant arm discontinuing before receiving sHDCT/ASCT. The main reasons for discontinuation included:
- Disease progression (12%)
- Adverse effects (6%)
- Withdrawal of consent (5%)
Secondary primary malignancies were observed in 18% of transplant arm patients and 14% of control arm patients, showing no significant difference between groups (P = .41).
Expert Perspective
Dr. Marc-Andrea Baertsch from University Hospital Heidelberg, the study's lead researcher, emphasized that the GMMG ReLApsE trial represents the only randomized clinical trial comparing sHDCT/ASCT with continuous novel agent treatment. The extended follow-up revealed a reduced effect of transplantation compared to initial findings, particularly in overall survival landmark analyses.
These findings provide important insights for treatment decision-making in relapsed/refractory multiple myeloma, suggesting that continuous novel agent therapy may be as effective as salvage transplantation in this patient population.
