ABSTRACT
Introduction: Cancer patients have been considered a high-risk population in the COVID-19 pandemic. We previously investigated risk of COVID-19 death in COVID-19 positive cancer patients during a median follow-up of 134 days, and identified the following risk factors: male sex, age >60 years, Asian ethnicity, hematological cancer type, cancer diagnosis for >2.5 years, patients presenting with fever or dyspnea, and high levels of ferritin and C-reactive protein (CRP). Here, we further investigate which factors are associated with a COVID-19 related death within 7 days of diagnosis. Methods: Using data from Guy's Cancer Centre and one of its partner trusts (King's College Hospital), we included 306 cancer patients with a confirmed COVID-19 diagnosis (February 29th-July 31st 2020). 72 patients had a COVID-19 related death (24%) of whom 35 died within 7 days (50%). Cox proportional hazards regression was used to identify which factors were associated with a COVID-19 related death <7 days of diagnosis. Results: Of the 72 cancer patients who had a COVID-19 related death, the mean age was 72 years (Standard Deviation (SD) 14). A total of 53 (74%) patients were men. 37 (52%) had a hematological cancer type, 47 (65%) had stage IV cancer, and 42 (58%) had been diagnosed with cancer more than 24 months before COVID-19 related death. In the group of patients who died within 7 days of diagnosis (n= 35), mean age was 73 years (SD 13.96), 24 (68%) were men, 20 (57%) had a hematological cancer type, 26 (74%) had stage IV cancer, and 24 (68%) had been diagnosed with cancer >24 months before COVID-19 diagnosis. Factors associated with COVID-19 related death <7 days of diagnosis were: hematological cancer (Hazard Ratio (HR): 2.74 (95% Confidence Interval (CI): 1.21-6.22)), 2-5 yrs since cancer diagnosis (HR: 4.81 (95%CI: 1.47-15.69)), and >5 yrs since cancer diagnosis (HR: 4.41 (95%CI: 1.38-14.06)). Additionally, patients who presented with dyspnea had increased risk of COVID-19 related death <7 days compared to asymptomatic patients (HR: 5.25 (95%CI 2.14-12.89)). CRP levels in the third tercile (146-528 mg/L) as compared to the first were also associated with increased risk of an early death due to COVID-19. Conclusion: From all the factors identified in our previous COVID-19 related death analysis, only hematological cancer type, a longer-established cancer diagnosis (2-5 years and more than 5 years), dyspnea at time of diagnosis and high levels of CRP were indicative of an early COVID-19 related death (within 7 days of diagnosis) in cancer patients.
ABSTRACT
Background: The role of upfront ASCT for NDTE MM remains under evaluation with high MRD rates following novel induction and consolidation (cons) strategies. K maintenance represents an alternative strategy to lenalidomide maintenance. The CARDAMON trial investigated K maintenance following KCd induction plus either ASCT or KCd cons. Methods: NDTE pts received 4 x KCd induction (K 20/56 mg/m2 biweekly, C 500 mg D 1,8,15, d 40mg weekly) before 1:1 randomisation to ASCT or 4 x KCd cons followed by 18 cycles K maintenance (56mg/m2 D1,8,15). Flow cytometric MRD (10-5) was assessed post induction, pre-maintenance and at 6 months maintenance. Primary endpoints were ≥VGPR post induction and 2-year PFS from randomisation. Secondary endpoints included improvements in disease response and MRD conversion following ASCT/ cons and maintenance. Results: 281 patients were registered, with 218 randomised to either ASCT or cons. The median PFS for ASCT was not yet reached vs 3.4 years for cons, with cons failing to show non-inferiority (difference in 2-year PFS 6.5%, 70% CI 1.0% to 11.1%). 196 patients received K maintenance (99 ASCT, 97 cons), 17 remain on treatment. A median of 16 cycles (1-18) were given over a median of 15.9 months (0-21.5). COVID-19 led to maintenance treatment interruptions in 41 (8 ASCT, 6 Cons) and treatment discontinuation in 15 (9 ASCT, 6 Cons). The median K dose given was 50.6mg/m2 and was similar across both arms (51.2 vs 49.4mg/m2, p=0.03). K maintenance was discontinued for PD in 14.1% (ASCT) vs 22.7% (cons), and for adverse events (AEs) in 7.1% (ASCT) vs 4.1% (cons). Most common AEs were hypertension and infections and more ≥G3 AEs were noted in ASCT vs cons (p=0.01). Patient/ clinician withdrawals from maintenance were low but occurred more in the ASCT arm (9.1% vs 1%). MRD neg patients post ASCT/ Cons had a longer PFS than MRD pos (p=0.002);with a higher MRD neg rate in the ASCT arm (53.6% vs 35.1% in Cons, p=0.01). MRD neg patients at 6 months post maintenance also had longer PFS (p=0.004 cf MRD pos patients);again with higher MRD neg rates in the ASCT arm (58.1% ASCT vs 40.5% Cons, p=0.02). There was no difference in PFS for MRD neg patients according to treatment arm from PBSCH, post-ASCT/ Cons or 6 months maintenance timepoints. Overall, 27.8% of MRD pos patients converted to MRD neg post ASCT/ Cons with more converting with ASCT (39.1% ASCT vs 16.1%, p=0.004). 23.5% of MRD pos patients converted to neg during maintenance (30.6% ASCT, 17.8%: p=0.2). Maintenance of MRD negativity over the first 6 months was similar between ASCT and Cons arms (p=0.3). There was no evidence that the timing of achievement of MRD negativity impacted PFS. Conclusions: K maintenance at 56mg/m2 weekly was deliverable and tolerable, with continued higher MRD neg rates at 6 months post-ASCT compared to post-Cons. However more ≥G3 AEs and discontinuations for AEs/ patient choice were noted for K maintenance after ASCT.
ABSTRACT
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.