Canadian perspective on managing multiple myeloma during the COVID-19 pandemic: lessons learned and future considerations.

The coronavirus disease 2019 (covid-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 has necessitated changes to the way patients with chronic diseases are managed. Given that patients with multiple myeloma are at increased risk of covid-19 infection and related complications, national bodies and experts around the globe have made recommendations for risk mitigation strategies for those vulnerable patients. Understandably, because of the novelty of the virus, many of the proposed risk mitigation strategies have thus far been reactionary and cannot be supported by strong evidence. In this editorial, we highlight some of the risk mitigation strategies implemented at our institutions across Canada during the first wave of covid-19, and we discuss the considerations that should be made when managing patients during the second wave and beyond.

A matched comparison of cyclophosphamide, bortezomib and dexamethasone (CVD) versus risk-adapted cyclophosphamide, thalidomide and dexamethasone (CTD) in AL amyloidosis.

Despite improvements in therapy amyloid light-chain (AL) amyloidosis, there are few studies comparing different regimens. Here we present a matched comparison with 69 patients in each cohort examining upfront therapy with cyclophosphamide, bortezomib and dexamethasone (CVD) vs cyclophosphamide, thalidomide and dexamethasone (CTD). On an intention-to-treat basis, the overall response rates were 71.0% vs 79.7% in the CVD and CTD arms, respectively, (P=0.32). A higher complete response (CR) rate was observed in the CVD arm (40.5%) vs CTD (24.6%), P=0.046. One-year overall survival (OS) was 65.2% and 66.7% for CVD and CTD, respectively (P=0.87). The median progression-free survival (PFS) was 28.0 and 14.0 m for CVD and CTD, respectively (P=0.039). In a landmark analysis assessing outcomes performed at 6 months, the CR rate with CVD was 59.6% vs 34.0% for CTD (P=0.03). The 1-year OS was 96% with CVD and 92% with CTD (P=0.40). The median PFS with CVD was not reached and was 19.2 m with CTD, P=0.028). In summary, both regimens are unable to overcome the high rate of early deaths in AL amyloidosis. However, CVD correlates with improved depth of response and superior PFS supporting its use in the frontline setting. Further optimisation and better supportive-care strategies are required to increase the proportion of patients fully benefiting from therapy.

Renal transplantation in systemic amyloidosis-importance of amyloid fibril type and precursor protein abundance.

Renal transplantation remains contentious in patients with systemic amyloidosis due to the risk of graft loss from recurrent amyloid and progressive disease. Outcomes were sought among all patients attending the UK National Amyloidosis Centre who received a renal transplant (RTx) between January 1978 and May 2011. A total of 111 RTx were performed in 104 patients. Eighty-nine percent of patients with end-stage renal disease (ESRD) due to hereditary lysozyme and apolipoprotein A-I amyloidosis received a RTx. Outcomes following RTx were generally excellent in these diseases, reflecting their slow natural history; median graft survival was 13.1 years. Only 20% of patients with ESRD due to AA, AL and fibrinogen amyloidosis received a RTx. Median graft survival was 10.3, 5.8 and 7.3 years in these diseases respectively, and outcomes were influenced by fibril precursor protein supply. Patient survival in AL amyloidosis was 8.9 years among those who had achieved at least a partial clonal response compared to 5.2 years among those who had no response (p = 0.02). Post-RTx chemotherapy was administered successfully to four AL patients. RTx outcome is influenced by amyloid type. Suppression of the fibril precursor protein is desirable in the amyloidoses that have a rapid natural history.