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The combination of panobinostat, bortezomib and dexamethasone (PanBorDex) is available as a treatment option for relapsed refractory multiple myeloma (RRMM) based on the PANORAMA-1 trial which investigated this triplet in early relapse. In routine clinical care, PanBorDex is used primarily in later relapses and is commonly administered in attenuated dosing schedules to mitigate the treatment-related toxicity. We set out to evaluate efficacy and safety outcomes with PanBorDex later in the disease course and evaluate the role of attenuated dosing schedules. This was a retrospective evaluation of patients treated in routine clinical practice between 2016–2019 across seven heamatology centres in the UK; patients who received at least one dose of PanBorDex were eligible for inclusion. The dosing schedule of panobinostat (10mg, 15mg or 20mg, twice or three times a week) and bortezomib (0.7mg/m2, 1mg/m2 or 1.3mg/m2 once or twice weekly) was as per treating physician choice. Patients received treatment until disease progression or unacceptable toxicity. The primary outcome is response rates according to IMWG criteria. Key secondary endpoints include progression-free survival (PFS) and overall survival (OS). Other secondary endpoints include rates of adverse events according to CTCAE criteria. In total, 61 patients were eligible for inclusion and received PanBorDex primarily as ≥5th line of treatment. One third of patients received PanBorDex at full dose, for the remaining two thirds, treatment was given in reduced dose intensities. The overall response rate was 44.2%, including 14.7% very good partial response (VGPR) rates; 68.8% of patients derived clinical benefit with stable disease or better. The median PFS was 3.4 months; non-refractory patients and those who achieved VGPR benefited from prolonged PFS of 11.4 months and 17.7 months, respectively. The median OS was 9.5 months. The triplet was associated with 45% and 18% incidence of grade 3–4 thrombocytopenia and diarrhea, respectively. [ABSTRACT FROM AUTHOR]

Treatment of transplant-ineligible (TNE) newly diagnosed multiple myeloma (NDMM) requires a balance between disease control and maintaining quality of life (QoL). Patients value treatment-free remission periods in this incurable condition, as they are associated with better QoL. We set out to study clinical outcomes of consecutive TNE NDMM patients in routine care treated in Thames Valley Cancer Network between 2009 and 2017. The primary outcome was the evaluation of the treatment-free interval (TFI) after 1st and subsequent lines of therapy in the total cohort and in individual subgroups, according to age (≤75 vs. >75 years), and co-morbidities using Charlson Co-morbidity Index (CCI): mild: 0–2 vs. moderate: 3–4 vs. severe: ≥5). Secondary outcomes include response rates, overall survival (OS) and progression-free survival (PFS) between subgroups: according to age and according to co-morbidities. In a total cohort of 292 patients, median TFI (IQR) was longest after first-line therapy 6.9 months (1.4–16.9), reducing after second line therapy to 1.8 months (.7–6.9), and after third line therapy to 0.6 months (0.2–1.5). Median TFI followed the same trend across the different subgroups, by age (≤75, >75 years) and by CCI (0–2, 3–4, ≥5). Overall response rate (ORR) to first line therapy for total cohort was 67%, with responses categorised as complete response (CR): 21%, very good partial response: 16%, partial response: 30%, stable disease: 18%, and progressive disease: 8%. ORR in individual subgroups by age were (≤75: 70% vs. >75: 63%), and by CCI (0–2: 65% vs. 3–4: 71% vs. ≥5: 77%). Median OS and PFS for the total cohort were (30.2 months, 95% CI: 23.8–36.9), and (9 months, 95% CI: 7.9–9.8), respectively. Patients aged >75 years showed a significant reduction in OS and PFS compared to those ≤75 years of age: OS (49.0 vs. 22.4 months, p<0.0001, HR: 2.08, 95% CI: 1.5–2.8), PFS (9.7 vs. 8.0 months, p<0.01, HR: 1.47, 95% CI: 1.1–1.9). Median OS was significantly reduced with worsening co-morbidities: (CCI 0–2: 52.4 months vs. CCI 3–4: 33.0 months vs. CCI ≥5: 24.0 months, p = 0.01, HR: 1.43, 95% CI: 1.1–1.9). Median PFS was significantly reduced in the severely co-morbid subgroup (CCI 0–2: 9.4 months vs. CCI 3–4: 9.6 months vs. CCI ≥5: 7.1 months, p = 0.025, HR: 1.3, 95% CI: 1.0–1.6). This study demonstrated that first line therapy in the TNE NDMM setting resulted in the longest TFI which was modest at a median of 6.9 months, and decreased significantly following subsequent lines of therapy and across the different subgroups by age and by co-morbidities. Therapy objective should be to maximise the benefit of first line treatment. We envisage that the recent shift towards a continuous therapeutic approach will benefit TNE patients in view of improved survival data demonstrated by a number phase 3 trials. When continuous therapy is not appropriate due to patient choice or toxicities, an efficacious (not limited to thalidomide and bortezomib) but tolerable first line FDT strategy, which can maximise TFI and maintain a good QoL, remains a reasonable alternative approach. [ABSTRACT FROM AUTHOR]