Thalidomide-Based Treatment Too Risky in Multiple Myeloma?

Thalidomide-based treatment, including maintenance therapy, could be an option for patients with recently diagnosed multiple myeloma who are eligible for autologous stem cell transplantation (auto-SCT) and have no access to proteasome inhibitors or lenalidomide.

This conclusion was drawn from long-term follow-up results of the HOVON-50 phase III trial, which previously showed improved event-free survival for thalidomide-containing induction and maintenance regimens in conjunction with melphalan and transplant after a median follow-up of 2 years.

“Although bortezomib-based induction therapy followed by lenalidomide maintenance is now the standard of care for recently diagnosed patients with multiple myeloma who are eligible for stem cell transplantation, our data support the use of thalidomide as part of induction regimens and maintenance therapy after stem cell transplantation in countries where cost and access to bortezomib and lenalidomide represent important challenges for patients with multiple myeloma and their physicians,” researchers led by Niels WCJ van de Donk, MD, of VU University Medical Centre, Amsterdam, Netherlands, and colleagues wrote in Lancet Oncology.

The HOVON-50 trial included 536 patients with recently diagnosed myeloma from 44 Dutch and Belgian hospitals. Patients were randomly assigned to either three 28-day cycles of vincristine, doxorubicin, and dexamethasone, or to the same regimen plus thalidomide instead of vincristine.

After undergoing stem cell harvest, patients received one or two more courses of treatment with transplantation. Those patients with partial response or better could continue on maintenance therapy.

The median follow-up for this long-term study was 129 months. At that time, event-free survival censored at allogeneic transplant was significantly longer in patients assigned thalidomide to those who were not (hazard ratio [HR], 0.62; 95% CI, 0.50–0.77; P < .0001).

At 10 years, the progression-free survival rate was 21% in the thalidomide groups compared with 9% in the control group.

Many patients in both arms who had not progressed by 10 years achieved a complete response (67% for thalidomide and 62% for control). The researchers noted that with this longer follow-up, no difference in overall survival was noted between the two arms.

“However, when results are adjusted for covariates, addition of thalidomide also increased overall survival compared with classical cytotoxic drugs and interferon alfa,” the researchers wrote.

About 40% of patient's assigned thalidomide had to stop therapy because of toxicity, 75% of whom had neuropathy. Because of this, the researchers wrote that “careful follow-up and timely dose adjustments are important to prevent the development of thalidomide-induced neurotoxicity.”

Skin reactions, fatigue and other symptoms also occurred in the intervention group. Less than one-third of patients (27%) in the control group discontinued therapy during maintenance with interferon alfa because of toxicity.

There was a similar rate of second primary malignancies in both groups.

Commenting of the study, Jesus San Miguel, director of clinical and translational medicine at Universidad de Navarra, Spain, told Cancer Network, “Long-term follow-up studies are very important and the present one reinforces the value of thalidomide for myeloma treatment. This study is particularly important for countries with limited resources.”