Transplantation Added to RVD Yields Longer PFS Than RVD Alone in Patients With MM

Among adults with multiple myeloma (MM), the combination of triplet therapy with lenalidomide, bortezomib, and dexamethasone (RVD) with autologous stem-cell transplantation (autoSCT) was associated with longer progression-free survival (PFS) than RVD alone, according to findings from a phase 3 trial.

A total of 873 patients with symptomatic MM received 1 cycle of RVD. These patients were then randomly assigned in a 1:1 ratio to receive 2 additional RVD cycles plus stem cell mobilization, followed by either 5 additional RVD cycles (RVD-alone group; n = 357) or high-dose melphalan plus autoSCT followed by 2 additional RVD cycles (transplantation group; n = 365). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point of the study was PFS.

At a median follow-up of 76 months, 328 events of disease progression or death occurred. The risk for disease progression or death was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.23 to 1.91; P <.001); median PFS was 46.2 months and 67.5 months, respectively. 

The percentage of patients with a partial response or better was 95% in the RVD-alone group and 97.5% in the transplantation group (P = .55); the percentage of patients with a complete response or better was 42% and 46.8%, respectively (P = .99).  The 5-year survival was 79.2% and 80.7% (HR for death, 1.10; 95% CI, 0.73 to 1.65).

Treatment-related adverse events (AEs) of grade ≥3 occurred in 78.2% in the RVD-alone group and 94.2% in the transplantation group. Serious RVD-related adverse events were reported in 144 patients in the RVD-alone group (40.3%) and 172 patients in the transplantation group (47.1%), and treatment-related serious infections were reported during maintenance therapy in 33 of 291 patients (11.3%) and 48 of 289 patients (16.6%), respectively.

“In adults with [MM], [PFS] was significantly longer among those who were assigned to the transplantation group than among those who were assigned to the RVD-alone group,” the study authors concluded.

 “In the absence of a demonstrated overall survival benefit, however, and in the context of considerations regarding real-world factors such as treatment burden, acute and long-term toxic effects, patient preference, and quality of life, these findings may be taken into account when making treatment decisions,” they added. 

Source:

Richardson P, Jacobus S, Weller E, et al. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. N Engl J Med. 2022 Jul 14;387(2):132-147. doi:1056/NEJMoa2204925.