Yago L. Nieto, MD, PhD, professor, Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses findings from a phase 2 trial investigating panobinostat (Farydak), gemcitabine, busulfan, and melphalan plus autologous stem cell transplant (ASCT) in patients with high-risk or relapsed/refractory multiple myeloma.

This trial enrolled 80 patients to 1 of 2 cohorts. The first cohort consisted of patients who were receiving a first transplant for relapsed/refractory disease or as frontline consolidation for disease with high-risk cytogenetics, Nieto says. The second cohort consisted of patients who were receiving a second transplant after progressing on a previous transplant, Nieto explains.

This trial showed that the combination of panobinostat, gemcitabine, busulfan, and melphalan plus ASCT was safe, with manageable toxicities, Nieto notes. This regimen was also associated with high overall response rates and complete response rates, at 67% and 40%, respectively, in cohort 1 and 93% and 64%, respectively, in cohort 2, Nieto emphasizes. Additionally, minimal residual disease (MRD) negativity rates improved after transplant in both cohorts, and MRD negativity conversion was associated with better outcomes, Nieto says. The MRD negativity rate increased from 8.5% to 23% after transplant in cohort 1 and from 34% to 55% in cohort 2.

The second part of this trial was a comparison between both cohorts of the study and a concurrent control cohort consisting of patients who were eligible for the trial but instead received off-trial transplant with either busulfan and melphalan or melphalan alone, Nieto explains. A matched pair analysis showed progression-free survival (PFS) superiority with the study regimen vs the control arm in patients receiving a first transplant, Nieto says. Conversely, the matched pair analysis of patients receiving a second transplant showed no significant difference in PFS between the study regimen and control arm, Nieto notes.

Based on these findings, the investigators concluded that panobinostat, gemcitabine, busulfan, and melphalan plus ASCT is more effective than standard-of-care transplant with busulfan and melphalan or melphalan alone in patients receiving a first transplant for relapsed/refractory or high-risk multiple myeloma, Nieto concludes.

Dr. Nieto has received research funding from Novartis, Secura Bio, AstraZeneca, and Affimed.

Yago L. Nieto, MD, PhD

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