Evolving Role of Daratumumab: From Backbencher to Frontline Agent

Potential ‘significance’ of monoclonal gammopathy of ‘undetermined significance’ during COVID-19 pandemic

“… Underlying ‘MGUS’, and clone-directed therapies could compromise vaccine efficacy Apart from the routine seasonal influenza, and pneumococcal vaccines, vaccination against SARS-CoV-2 when available, must be considered for patients with MGCS ⁎⁎⁎ Bortezomib reduced the post-vaccine protective antibody titer by ~30% in patients with SLE [ 26 ] Consider usual SARS-CoV-2 vaccination in MGCS patients on a PI ⁎⁎⁎ DARA did not affect the antibody response to seasonal influenza vaccine in patients with heavily pre-treated MM 27 Consider usual SARS-CoV-2 vaccination for patients with MGCS on DARA. Rituximab causes profound B-cell depletion, and complete B-cell recovery could take 6–12 months after the last dose ⁎⁎⁎⁎28 Consider SARS-CoV-2 vaccination either prior to, or atleast 6-months after the last dose of Rituximab in MGCS patients IMiDs were shown to augment the vaccine response [ 29 ] Consider usual SARS-CoV-2 vaccination in MGCS patients on IMiDs + Other prophylactic medications Acyclovir is potentially nephrotoxic Continue acyclovir for HZ prophylaxis with PI and DARA, albeit dose-modified according to renal function for MGRS patients Dialysis for MGRS patients Maintain social distancing, and adequate sanitization in the nephrology dialysis units Consider shifting patients from hemodialysis to peritoneal dialysis after nephrology consultation Treatment considerations for patients with MGCS during COVID-19 pandemic General measures MGCS could represent an immunocompromised population, and may be at a higher risk of infection and death during COVID-19 Consider general hand hygiene, and social distancing Consider COVID-19 by PCR-based assays before initiating any immunosuppressive treatment for new MGCS cases [ 24 ] Modifications of clone-directed chemotherapy regimens [ 24 , 31 , 32 ] CyBorD ++ 24 Consider SC bortezomib instead of IV route Reduce Dexamethasone dose to 20 mg/week instead of 40 mg/week Consider oral cyclophosphamide instead of IV route Consider renal modification of cyclophosphamide dose Consider 2-weekly bortezomib administration instead of weekly administration +++ DARA was shown to be safe and effective in patients with certain MGRS entities [ 30 ] …”

“…Therefore, like patients with ‘cancer’, MGCS patients also have a higher risk of contracting, and dying from COVID-19. Considerations for prophylaxis, and treatment for patients with MGCS during COVID-19 pandemic are summarized in Table 1 [ [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] ]. In conclusion, although research during COVID-19 pandemic has focused on cancer patients, MGUS does have potential clinical significance during the current COVID-19 pandemic.…”

Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials

“…Despite the enhanced cytotoxicity on myeloma cells, better survival results, and therapeutic response, safety concerns arise 36 as the target of this antibody is expressed on haematopoietic cells 37 . In NDMM, both all grade and grade 3–4 lymphopenia (moderate certainty) and neutropenia (low certainty) were more likely to appear in patients on daratumumab.…”

“…Besides the bone marrow, other tissues, like peripheral and central neurons, also express CD38 which could raise clinical concern 37 . A previous meta-analysis demonstrated that the risk for peripheral neuropathy does not increase with the addition of daratumumab 36 .…”

Cardiac Amyloidosis Therapy: A Systematic Review

“…New therapies for relapsed/refractory MM in the advanced cardiac AL amyloidosis include Daratumumab, a human IgG1k monoclonal antibody targeting the CD38 antigen on plasma cells (also expressed in AL amyloidosis) [24,25]. Venetoclax is a BH3-mimetic used for chronic lymphocytic leukemia (CLL), and has a proven role in patients with translocation t (11;14), most commonly associated with AL amyloidosis.…”