Tandem Meetings 2023 | Phase II study of panobinostat/GemBuMel with autoSCT in high-risk or R/R multiple myeloma

This was a Phase II study we undertook to test the hypothesis that we had developed in our lab that Panobinostat, which is an HDAC inhibitor approved in myeloma, was synergistic with GemBuMel, which is a gemcitabine busulfan and melphalan, which is a regimen we have been doing quite a bit of work with in myelomas and lymphomas.

So, so in this study we enrolled patients with high risk or refractory relapsed myeloma in two separate cohorts. Cohort one was patients getting a stem cell transplant for the first time, and that included patients getting a transplant for relapsed disease or patients getting a consolidation transplant after frontline therapy for high risk disease. The second cohort were patients getting a second transplant. That is, patients who had previously received a transplant and had relapsed afterwards. So we enrolled a total of 80 patients.

We saw the study was safe in patients with with measurable disease at transplant. The response rate and CRS were significant. The CRS were around 40 to 50% and response rate between 60 and 70%. Importantly, we saw that the incidence of minimal residual disease or MRD improved significantly after transplant in both cohorts. That is, patients receiving either a first transplant or a second transplant. And that improvement of the MRD, measured by multiparametric flow cytometry, which has a sensitivity of ten to the minus fifth, improvement of the MRD conversion to MRD negativity was associated with with better outcomes. And that’s just something that confirms prior observations in transplant and non-transplant settings.

In a second step, we compared the outcomes of patients in both cohorts with all other concurrent patients who are eligible for the trial, but instead received standard of care melphalan or BuMel off-study at our center. So we did a matched pair analysis and we saw that in the subset of patients receiving a first transplant, studypatients who had had been treated with panobinostat/GemBuMel had significantly improved progression free survival compared to control patients, and that applied to both patients control patients who had been treated with BuMel and with melphalan. In contrast, we saw no differences in progression-free or overall survival for the subsets of patients receiving a second transplant.