A retrospective single-centre cohort study of the efficacy and safety of daratumumab with bortezomib and dexamethasone therapy for previously treated multiple myeloma

Content: Daratumumab, bortezomib and dexamethasone (DVd) is a therapy that has demonstrated significant clinical activity in relapsed/ refractory multiple myeloma (RRMM). In April 2019, it was approved by NICE. In June 2020, subcutaneous (SC) daratumumab gained EMA approval. This is a real-world retrospective study of 21 patients with RRMM who started DVd treatment between April 2019 and November 2020 at Guy's Hospital, London. Clinical characteristics, response rates and treatment emergent toxicity were reviewed using electronic records;response outcomes were assessed for patients who received ?1 cycles. The median age at the start of therapy was 61 (range 42-86), with 13 (61.9%) male patients. Clinical characteristics are shown in Table 1. Seventeen (81%) patients had 1 previous line of therapy: 5 (29.4%) VMP (bortezomib, melphalan, prednisone), 5 (29.4%) VTd (bortezomib, thalidomide, dexamethasone), 2 (11.8%) VCd (bortezomib, cyclophosphamide, dexamethasone), 1 (5.9%) CRd (bortezomib, lenalidomide, dexamethasone) and 4 (23.5%) a clinical trial. Four (19%) had 2 prior lines, including a clinical trial in all cases. Twelve (57.1%) had undergone autologous stem cell transplant. Overall, 18/21 (85.7%) patients had been exposed to bortezomib: overall response rate (ORR) was 88.9% and 1/18 (5.6%) was bortezomib-refractory in 1st line. Median progression free survival (PFS) and median treatment-free interval were 44.8 and 36 months, respectively. All patients had progression and 1 (4.8%) extramedullary disease prior to starting DVd. Median time on treatment was 9.6 months (0.2-18.2), with a median number of cycles of 12 (2-20). Six (28.6%) patients discontinued therapy: 4 (66.6%) due to progressive disease, 1 (16.7%) for patient's choice and 1 (16.7%) died on treatment (due to SARs-CoV-2-related pneumonia). At a median follow-up of 11 months (1.8-20.5), 20 (95.2%) patients have completed ?1 cycles. ORR is 85%, with very good partial response (VGPR) in 7 (35%) patients;only 1 (4.8%) patient had no response. The patient who was bortezomib-refractory in 1st line has a partial response (PR) so far. Median time to PR in the population is 36 days (15 67). PFS and overall survival (OS) rates are 76% and 93% at 11 months. Daratumumab administration was SC in 6 (28.6%) patients, and was switched from intravenous (IV) to SC during treatment in 8 (38.1%) patients. Six (28.6%) patients had a first-dose infusion related reaction (IRR) with daratumumab, in all cases being IV. In 2 (33.3%) cases it was grade ?3 and infusion could be resumed (both consisting of hypertension). Common (?15%) AEs were: lymphopenia (81%), anaemia (71.4%), thrombocytopenia (61.9%), peripheral sensory neuropathy (38.1%) and infections (28.6%), most of them SARs-CoV2 related (50%). Grade ?3 AEs happened in 10 (47.6%) patients. Three (30%) developed thrombocytopenia, 1 (10%) anaemia, 3 (30%) neutropenia and 6 (60%) lymphopenia. Moreover, 3 (30%) patients had SARs-CoV2-related pneumonia (in one of them leading to death) and another one (10%) sepsis secondary to jaw infection. Daratumumab combined with bortezomib and dexamethasone in RRMM demonstrates encouraging outcome results in our centre, similar to those exposed in the analysis of the phase III CASTOR study. It is expected that as more patients are treated and with a longer follow-up, the survival rates will improve. There is an acceptable safety profile in our population, with no IRRs to the moment since the introduction of SC daratumumab. Table 1. Clinical characteristics of the population.