Panobinostat plus gemcitabine, busulfan, and melphalan (Pano/GBM) is safe and effective as conditioning prior to transplant in patients with high-risk or relapsed/refractory multiple myeloma (MM), according to a presentation at the Tandem Meetings 2023. 

Pano/GBM plus autologous stem cell transplant (ASCT) produced responses and improved minimal residual disease (MRD) negativity in these patients in a phase 2 trial ( Identifier: NCT02506959). 

The trial included 80 patients with 1 or more of the following factors: primary refractory MM, relapsed/refractory MM, high-risk cytogenetics, multiple prior relapses, or relapse after previous ASCT. All patients were 18-65 years of age, had a performance status score of 0-2, and had adequate renal, hepatic, pulmonary, and cardiac function. 

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Patients were separated into 2 cohorts. The ASCT-1 cohort included 48 patients receiving their first frontline ASCT or first ASCT for relapsed/refractory MM. The ASCT-2 cohort included 32 patients receiving a second salvage ASCT. All patients received Pano/GBM prior to transplant.

In both cohorts, grade 2 and 3 toxicities included mucositis (52% grade 2, 17% grade 3), diarrhea (18% and 9%, respectively), skin rash (14% and 1%), and asymptomatic transaminase elevations (14% and 21%). Two treatment-related deaths occurred in the ASCT-2 cohort — 1 due to sepsis and 1 due to RSV pneumonia.

In the ASCT-1 cohort, the overall response rate (ORR) was 67%, and the complete response (CR) rate was 40%. In the ASCT-2 cohort, the ORR was 93%, and the CR rate was 64%. 

In the ASCT-1 cohort, MRD negativity improved from 8.5% before ASCT to 23% after (P <.0001). In the ASCT-2 cohort, MRD negativity improved from 34% to 55% (P =.02).

At a median follow-up of 51 months, the median progression-free survival (PFS) was 45 months for ASCT-1 patients who received a frontline ASCT, 21 months for patients who received ASCT-1 for relapsed/refractory disease, and 32 months in the ASCT-2 cohort. 

The researchers also evaluated PFS and overall survival (OS) in study participants compared with matched control patients who received conditioning with high-dose melphalan or busulfan plus melphalan (BuMel). 

PFS was significantly better among all patients in the Pano/GBM cohort than among all control individuals (P =.0077). However, there was no significant difference in OS (P =.5)

For patients who underwent ASCT-1, the PFS was significantly better with Pano/GBM than with BuMel or high-dose melphalan (P =.016). There was no significant difference in OS (P =.72).

For those who underwent ASCT-2, there was no significant difference in PFS (P =.84) or OS (P =.52) between patients who received Pano/GBM and those who received BuMel or high-dose melphalan.

When Pano/GBM was compared with BuMel only in ASCT-1, there was a significant improvement in PFS (P <.0001) and OS (P <.0001) with Pano/GBM.

“Panobinostat and GemBuMel, which exploits the synergy between HDAC inhibitors and GemBuMel, is a safe regimen, and an effective one, in relapsed/refractory or high-risk myeloma,” said study presenter Yago Nieto, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston.

Disclosures: Dr Nieto disclosed relationships with Novartis, Secura Bio, AstraZeneca, and Affimed.


Nieto Y, Yang Z, Kundu S, et al. Safety and efficacy of a new high-dose chemotherapy regimen of panobinostat, gemcitabine, busulfan and melphalan (Pano/GBM) with autologous stem cell transplant (ASCT) for patients with high-risk or refractory/relapsed myeloma – Matched pair comparisons with a concurrent control cohort. Tandem Meetings 2023. February 15-19, 2023. Abstract 38.

This article originally appeared on Cancer Therapy Advisor