High-Dose Therapy Before Transplant Effective in Refractory Myeloma

Undergoing autologous hematopoietic stem cell transplantation (auto-HCT) was effective and safe in patients with refractory multiple myeloma, including those patients who are refractory to both proteasome inhibitors and immunomodulatory agents, according to a retrospective study.

“Patients who have refractory myeloma present a unique treatment challenge in which clinical outcomes remain suboptimal despite the deployment of novel agents,” wrote researchers led by Lauren W. Veltri, MD, of the University of Texas MD Anderson Cancer Center, Houston, in Cancer. “In the current report on our institutional experience in patients who have less than a partial response before auto-HCT, we demonstrate that high-dose therapy followed by auto-HCT is an effective therapy to induce response, even in patients who are refractory to novel agents.”

Novel agents for myeloma, such as proteasome inhibitors and immunomodulatory agents, can induce response in 80% or greater of patients; however, some patients will fail to respond or become refractory to these drugs. In these patients, researchers are still trying to establish an optimal course of treatment.

Veltri and colleagues conducted a retrospective study of 233 patients with refractory myeloma who underwent autologous transplant between March 2000 and October 2015.

Patients who were refractory to at least one proteasome inhibitor and one immunomodulatory agent were classified as double-refractory (45%). Patients with double-refractory disease were significantly older (P = .005), were more likely to be treated with chemoembolization (P = .002), more likely to be treated with a triplet induction regimen (P < .001), and to receive more lines of therapy before transplant (P < .001) compared to patients without double-refractory disease.

The overall response rate was 80% with patients with or without double-refractory disease having similar response rates.

“These response rates are similar to rates reported in other studies evaluating patients with refractory disease who underwent auto-HCT, demonstrating the clear role and effectiveness of high-dose melphalan in this patient population,” the researchers wrote.

With a median follow-up of 42 months, 188 patients (81%) had at least partial response, including 79% of patients with double-refractory disease and 82% of patients with non–double refractory disease. About one-quarter (22%) of patients in both groups had a near complete response or better (24% double-refractory; 21% non–double-refractory).

“Our double-refractory multiple myeloma group had shorter progression-free survival and overall survival compared with those in the non–double-refractory group, although the difference was not statistically significant,” the researchers wrote, also noting the differences in patient characteristics between the two groups.

The median progression-free survival was 17.6 months for all patients. In the double-refractory group, the median progression-free survival was 14.4 months compared with 18.2 months for non–double-refractory disease. The 2-year progression-free survival was 38% (35% in the double-refractory group and 40% in the non–double-refractory group).

The median overall survival was 48 months. Patients in the non–double-refractory group had a median overall survival of 56.6 months compared with only 38.9 months in double-refractory disease.

“Overall, our data highlight that auto-HCT is an effective therapy for inducing response and possibly prolonging survival in patients with double-refractory disease,” the researchers wrote. “However the role of auto-HCT in this scenario will continue to evolve as more effective immunomodulatory agents, proteasome inhibitors, and other agents become available.”