HOVON Trial: Hematopoietic Cell Transplant Superior to Novel Agents in Multiple Myeloma

CHICAGO–New data from the large, randomized, phase III HOVON trial suggest that upfront autologous hematopoietic cell transplantation (AHCT) should still be the treatment of choice in younger patients with newly diagnosed multiple myeloma (MM).

The role of AHCT in MM has been called into question recently, as a number of new myeloma drugs have gained approval in the last year, but data from this trial, presented at the 2016 American Society of Clinical Oncology Annual Meeting by Michele Cavo, MD, from the Seràgnoli Institute of Hematology at the University of Bologna in Italy, showed that younger patients undergoing AHCT experienced longer progression-free survival than those treated with bortezomib-based chemotherapy.

“Our findings show that AHCT should remain the preferred treatment for patients with MM ≤65 years,” Dr. Cavo said during his discussion of the results. “While transplant-free treatment with novel agents remains an intriguing prospect, the reality is that stem cell transplant remains a powerful and proven approach, and, with novel agents playing a supporting role, it is more effective than ever.”

A total of 1,266 patients (≤65 years) with newly diagnosed MM were enrolled into the trial between February 2011 and April 2014. In the first stage of the study, patients underwent induction therapy with bortezomib–cyclophosphamide–dexamethasone, then were randomly assigned to receive:

  • 4 cycles of bortezomib/melphalan/prednisone (VMP; n=512)
  • high-dose melphalan with single- or double-AHCT (HDM; n=754)

In the second stage, patients in both groups were randomized to consolidation therapy with bortezomib/lenalidomide/dexamethasone or no consolidation therapy. All patients received maintenance therapy with lenalidomide until disease progression or intolerable toxicity.

A first pre-specified interim analysis was performed in January 2016, after at least 33 percent of the required events had been observed.

The median follow-up during the first phase of the study was 23.9 months. Though the median progression-free survival (PFS; the study’s primary endpoint) had not been reached, patients in the HDM cohort had a significantly prolonged PFS compared with those in the VMP cohort. Transplant was associated with a 24 percent lower risk of disease progression versus chemotherapy (hazard ratio [HR] = 0.76; 95% CI 0.61-0.94; p=0.008) and the PFS benefit was evident across predefined patient subgroups, including:

  • Patients with advanced disease (defined as International Staging System stage 3): HR=0.52 (95% CI 0.32-0.84; p=0.008)
  • Patients with high-risk cytogenetics (including t4;14, del17p, del1p, and 1q gain): HR=0.72 (95% CI 0.54-0.97; p=0.028)

More patients in the HDM cohort achieved a very good partial response or better compared with VMP (84% vs. 74%; odds ratio = 1.9; 95% CI 0.42-2.54; p<0.0001), and, in a Cox regression analysis, HDM was confirmed as an independent predictor of prolonged PFS (HR=0.61; 95% CI 0.45-0.82; p=0.001).

Though a high-quality response is an important indicator for survival, the study authors noted that data on overall survival is not yet mature, with no differences between study groups at the time of analysis. Future analyses will compare the overall survival, toxicity, and quality of life associated with AHCT and novel agents.

Reference

Cavo M, Palumbo A, Zweegman S, et al. Upfront autologous stem cell transplantation (ASCT) versus novel agent-based therapy for multiple myeloma (MM): A randomized phase 3 study of the European Myeloma Network (EMN02/HO95 MM trial). Abstract #8000. Presented at the 2016 American Society of Clinical Oncology Annual Meeting, Chicago, IL, June 3, 2016.

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