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3203 Panobinostat in Combination with Bortezomib and Dexamethasone for Heavily Pre-Treated Myeloma: A UK Real-World Multi-Centre Cohort

Program: Oral and Poster Abstracts
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster III
Hematology Disease Topics & Pathways:
Adult, Non-Biological, Diseases, Therapies, chemotherapy, Adverse Events, Study Population, Clinically relevant
Monday, December 7, 2020, 7:00 AM-3:30 PM

Nadjoua Maouche1*, Bhuvan Kishore2*, Bhatti Zara2*, Supratik Basu3*, Farheen Karim3*, Sharadha Sundararaman3*, Freya Collings4*, Tseu Bing5*, Heather Leary6*, Noel Ryman7*, Udaya Reddy7*, Grant Vallance1*, Jaimal Kothari1*, Faouzi Djebbari1* and Karthik Ramasamy1

1Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
2University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
3The Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom
4Great Western Hospitals NHS Foundation Trust, Swindon, United Kingdom
5Buckinghamshire Healthcare NHS Trust, Bucks, United Kingdom
6Milton Keynes University Hospital NHS Foundation Trust, Milton Keynes, United Kingdom
7Hampshire Hospitals NHS Foundation Trust, Basingstoke, United Kingdom

Panobinostat (Pan), the first in-class histone deacetylase inhibitor is approved in combination with bortezomib (Bor) and dexamethasone (Dex) for relapsed/refractory multiple myeloma (RRMM) after ≥ 2 prior lines of therapy, including Bor and an IMiD, based on data from PANORAMA-1 trial. The trial excluded patients who are refractory to prior proteasome inhibitors (PIs). In clinical practice, PanBorDex is often introduced as 5th or later line of therapy using a range of pre-planned attenuated dosing schedules to maintain therapy and improve tolerability. We conducted a UK multicentre retrospective study to evaluate efficacy and toxicity outcomes of PanBorDex in a heavily pre-treated, myeloma cohort treated in routine care.

Sixty two patients were eligible for inclusion, of whom 58.1% were male, 46% were ISS 3 staging and 32.3% had a high cytogenetic risk (HR), defined as one or more of the following: t(4;14), t(14;16) , del(17p), t(14;20), 1q gain. Median age was 72 years (IQR 62-76 years). Median time from diagnosis was 5.6 years.

Median number of prior therapies was 4 (range 1-7); 98.4% of patients were PI-exposed, all patients received a prior IMiD. 46.8% of patients were PI-refractory, 82.3% were IMiD-refractory, and 43.5% were double refractory.

Patients received a median of 4 cycles (IQR 2-8). Eighteen patients (29%) completed ≥8 cycles. Twenty patients (32.3%) initiated PanBorDex at full dosing, and the remainder at a reduced dose or frequency or both of Pan and/or Bor. The overall response rate in the total cohort was 45%; VGPR, PR and PD rates were 14.5%, 30.6%, and 30.6%, respectively.

At a median follow up of 35.9 months, median PFS for the total cohort was 5.1 months (95% CI 2.0-8.1months) (Figure A). Median OS was 9.5 months (95% CI 5.5-13.4months) (Figure B). Median PFS according to depth of response was 6.6 months and 17.7 months for PR and ≥VGPR, respectively (Figure C). PFS was significantly shorter in double refractory compared to non-PI and non-IMiD-refractory patients (2.1 vs 11.4 months, p=0.001) (Figure D). Patients who were either PI-refractory or IMiD- refractory only had a median PFS of 7.2 months. HR cytogenetics subgroup demonstrated a very short median PFS of 2.2 months (Figure E).

Most commonly observed grade 3/4 adverse events (AEs) were thrombocytopenia (45.1%) and diarrhoea (17.7%). Other any grade AEs included infections (32%), fatigue (21%) and peripheral neuropathy (21%). 25 patients had a baseline ECGs then repeat ECGs during therapy; 2 patients had QTcF prolongations (>60 msec) from baseline, and both had pre-existing heart failure.

AEs led to discontinuation of either Pan or Bor or both in 11.3%, 1.6% and 17.7% of patients respectively. Dose reductions (at least one) of Bor or Pan or both were introduced in 8%, 16.1% and 22.6% of patients respectively. The mean relative dose intensity for Bor and Pan were 67.5% and 64.2%, respectively.

Our cohort is characterised by more heavily pre-treated and refractory myeloma patients compared to participants of PANORAMA-1 trial. Median PFS is consistent with 5.4 months reported in PANORAMA-2 study investigating this combination is Bor-refractory patients. These results are consistent with outcomes observed with pomalidomide and dexamethasone, and with daratumumab monotherapy when used in similar heavily pre-treated cohort. Lower rates of grade 3/4 AEs in this cohort can be explained by dose attenuation compared to the trial cohort.

Disclosures: Maouche: Janssen: Other: conference fees; Abbvie: Other: conference fees; Takeda UK: Consultancy, Honoraria, Other: Grant, conference feed, Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau. Kishore: Celgene: Other. Collings: Takeda: Speakers Bureau; Celgene: Speakers Bureau. Vallance: Jazz Pharmceuticals: Other. Ramasamy: Oncopeptides: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

*signifies non-member of ASH