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ASCO 2016: Autologous Stem Cell Transplant Remains Relevant in Multiple Myeloma, Even in Era of Novel Agents

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Key Points

  • While median progression-free survival was not yet reached, the data showed that disease in patients who received stem cell transplants progressed more slowly than in those who received VMP therapy without transplant.
  • Among patients who had not yet experienced disease progression, those in the autologous stem cell transplant arm had a 24% lower risk of progressing at any future time point compared to those not receiving transplant.
  • Patients with advanced disease randomized to the autologous stem cell transplant arm had a lower chance of progressing at the next analysis; among patients with certain high-risk genetic factors, transplant was associated with a lower chance of future progression compared to VMP therapy without transplant. Those receiving autologous stem cell transplant were also more likely to achieve a high-quality response to treatment, an important indicator of longer survival. 

Early findings from a phase III clinical trial (EMN02/HO95 MM) showed that patients with multiple myeloma who received an autologous stem cell transplant survived longer without disease progression than those who received only chemotherapy using novel agents. This is the largest study reported to date aimed at comparing autologous stem cell transplant with a bortezomib (Velcade)-based regimen alone in patients younger than 65 years. The study was featured in a press briefing today and will be presented by Cavo et al on Friday, June 3, at the 2016 ASCO Annual Meeting in Chicago (Abstract 8000).

Autologous stem cell transplant is an intensive procedure in which a patient’s blood-forming stem cells are harvested from the blood and stored. After treatment with high-dose chemotherapy, the stem cells are given back to the patient.

The proteasome inhibitor bortezomib was approved by the U.S. Food and Drug Administration (FDA) in 2008 for upfront treatment of multiple myeloma. Since then, bortezomib has been incorporated into the standard treatments for patients with newly diagnosed multiple myeloma, whether or not they are able to undergo autologous stem cell transplant. For patients younger than 65, however, the continued need for stem cell transplant has been debated in the era of novel agents, such as bortezomib (patients older than 65 are often unable to undergo transplant).

“Our findings show that autologous stem cell transplant should remain the preferred treatment for patients with multiple myeloma aged 65 and under,” said lead study author Michele Cavo, MD, Head of the Seràgnoli Instutite of Hematology at the University of Bologna. “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.”

Study Details

The randomized phase III study included 1,266 patients who were newly diagnosed with multiple myeloma. Following induction therapy with bortezomib/cyclophosphamide/dexamethasone, patients were randomly assigned to receive either bortezomib/melphalan/prednisone (VMP) or high-dose melphalan followed by single autologous stem cell transplant. (In treatment centers with a standard policy of performing two [double] autologous stem cell transplants, patients were randomly assigned to either VMP or single transplant or double transplant.)

In the second stage of the study, patients in both groups were randomly assigned to consolidation therapy with bortezomib/lenalidomide (Revlimid)/dexamethasone or no consolidation therapy. All patients received maintenance therapy with lenalidomide until disease progression or intolerable toxicity. A planned interim analysis was performed in January 2016.

Study Findings

At the time of the analysis, median follow-up after the first treatment randomization was 2 years (23.9 months). While median progression-free survival was not yet reached, the data showed that disease in patients who received stem cell transplants progressed more slowly than in those who received VMP therapy without transplant. Among patients who had not yet experienced disease progression, those in the transplant arm had a 24% lower risk of disease progressing at any future time compared to those not receiving transplant.

The benefit of transplant was confirmed in a further multivariate analysis and was even greater among certain patients at high risk of early progression. Patients with advanced disease (according to International Staging System III) randomized to the autologous stem cell transplant arm had a 48% lower chance of disease progression at the next analysis compared to those not receiving transplant. Among patients with certain high-risk genetic factors, transplant was associated with a 28% lower chance of future progression compared to VMP therapy without transplant. In comparison with patients who did not have a transplant, those receiving autologous stem cell transplant were also more likely to achieve a high-quality response (at least 90% tumor cell mass reduction) to treatment (74% vs 84%, respectively), which is an important indicator of longer survival.

Interim analysis of data related to the second randomization to consolidation therapy or no consolidation therapy is not yet complete. The study is ongoing, and future analyses will assess overall survival, toxicity, and quality of life, as well as other measures.

ASCO Perspective

“Even in an age of novel therapies, proven approaches can retain their value. This study demonstrated that combining the best of both worlds—initial therapy with a novel agent followed by stem cell transplant—resulted in the best patient outcomes,” commented ASCO President Julie M. Vose, MD, MBA, FASCO.

This study received funding from the Haemato Oncology Foundation for Adults in the Netherlands (HOVON).

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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