Second AHCT, RVD Consolidation Post-AHCT Intervention in Myeloma?

Standard treatment with high-dose melphalan and autologous hematopoietic transplantation (AHCT) followed by lenalidomide maintenance resulted in similar survival for patients with multiple myeloma as several other more intensive approaches, such as tandem AHCT or AHCT, followed by four cycles of lenalidomide, bortezomib, and dexamethasone (RVD), according to a recent study. 

This was true for patients with high-risk or standard-risk disease, reported Edward A. Stadtmauer, MD, of the University of Pennsylvania, and colleagues in the Journal of Clinical Oncology.

“Single AHCT followed by lenalidomide remains the standard of care,” the researchers wrote. “Greater than 80% of patients were alive at 38 months, which highlights excellent contemporary outcomes of patients with multiple myeloma when treated with a standard approach of a multidrug induction followed by AHCT consolidation and maintenance.”

In the study, patients aged 70 or younger with symptomatic myeloma within 12 months of starting therapy and without progression, were randomly assigned to standard care of AHCT plus lenalidomide (n = 257), tandem AHCT/AHCT plus lenalidomide (n = 247), or AHCT plus four cycles of RVD plus maintenance lenalidomide (n = 254). Eighteen percent of patients were in complete remission at the time of the study.

The 38-month progression-free survival was similar between the three arms at 58.5% for tandem transplant, 57.8% for AHCT plus RVC, and 53.9% for AHCT plus lenalidomide. Similarly, overall survival at 38 months was 81.8%, 85.4%, and 83.7%, respectively, for the three arms.

Overall, the rates of grade 3–5 toxicities were similar across the three study arms. However, a higher number of infection occurred in the first year in patients assigned to tandem AHCT. Despite this difference, quality of life improved equally for patients on all three arms at 1 year post-transplant compared with baseline.

The researchers documented nonadherence rates of 32% for second transplant and 22% for AHCT plus RVD. Although these rates were within the 40% threshold defined by the protocol as a stopping rule, the researchers acknowledged that they were high.

“Nevertheless, there was no difference between groups in the intent-to-treat outcomes and an earlier ad hoc as-treated analysis (data not shown) of the progression-free survival of the three groups, suggesting that this degree of nonadherence did not significantly dilute the effect of these interventions,” the researchers wrote.