SAN DIEGO -- Despite the success of novel targeted agents in newly diagnosed multiple myeloma, an upfront stem cell transplant remains the best treatment choice, a researcher said here.

In a large randomized clinical trial, European investigators compared two forms of intensification therapy: high-dose melphalan (HMD) plus an autologous stem cell transplant or standard-dose bortezomib-melphalan-prednisone (VMP), according to Michele Cavo, MD, PhD, of the Bologna University School of Medicine in Italy.

After a median follow-up of nearly 32 months, the median progression-free survival (PFS) had not been reached for those getting a transplant but was 42.5 months for those getting the VMP regimen, Cavo reported at the American Society of Hematology (ASH) annual meeting.

For fit patients with newly diagnosed disease, "upfront HDM and autologous stem cell transplant continues to be the reference treatment ... even in the novel agent era," Cavo concluded.

The novel agents are good and play an important role in induction therapy, including in this study, commented Mehdi Hamadani, MD, of the Medical College of Wisconsin in Milwaukee, who was not involved in the study but who co-moderated the ASH session.



But it is still too early stop performing stem cell transplants, he told MedPage Today.
"We don't have good enough data to conclude that transplants are dispensable," he said. He noted that most trials looking at the issue have been powered to evaluate PFS, adding that he's looking forward to seeing meta-analyses that will allow determination of overall survival.

So far, "we continue to see better disease control with transplant," he said.
In the current era, the question is what to do after an induction phase with novel agent-based therapy, Cavo noted.
His group enrolled more than 1,500 patients with symptomatic multiple myeloma from February 2011 to April 2014. Cavo was reporting on 1,192 patients evaluable when a pre-specified interim analysis was triggered earlier this year.
Patients were given four cycles of bortezomib (Velcade) plus cyclophosphamide and dexamethasone as induction therapy and then randomly assigned to HMD and transplant or VMD.

The primary endpoint of the study was PFS and the investigators found that, at 3 years, 35% of transplant patients had progressed compared with 42.9% of those getting the VMD regimen.

The difference yielded a hazard ratio for progression of 0.73 (95% CI 0.6100.88).
The pattern was similar in all pre-specified subgroups, although not significantly so in some.
A quarter of the patients in each arm had high-risk cytogenetics, Cavo said, and in those participants, the pattern was exaggerated: Median PFS was 42.3 months for transplant and 20.3 months for VMD (HR 0.53).

In a multivariate analysis, two factors significantly predicted PFS: standard risk genetics (HR 0.688), and assignment to transplant (HR 0.691).

The patients in the transplant arm had better response rates as well, he said.
In the VMD arm, 18.2% of patients had a stringent complete response, 25.3% had a complete response, and 30.4% had a very good partial response, compared with 17%, 25.3%, and 43.2%, respectively, for transplant.
Cavo noted that significantly more patients fell into one of those three groups in the transplant arm -- 85.5% versus 73.8%.

Also, 11.3% of VMD patients had less than a partial response, compared with 3.3% of those getting a transplant.
As might be expected, patients in the transplant arm had higher rates of anemia, neutropenia, and thrombocytopenia, as well as gastrointestinal issues, mucositis, febrile neutropenia, and sepsis.

On the other hand, the VMP regimen was associated with higher rates of peripheral neuropathy and fatigue, Cavo said. "Results of this phase III study, the largest so far reported, support the conclusion that upfront ASCT still continues to be the reference treatment for fit patients with [newly diagnosed multiple myeloma], even in the novel agent era," the authors concluded.