Preemptive therapy for cytomegalovirus reactivation after daratumumab-containing treatment in patients with relapsed and refractory multiple myeloma

Nakagawa, Ryo; Onishi, Yasushi; Kawajiri, Akihisa; Onodera, Koichi; Furukawa, Eijiro; Sano, Sayaka; Saito, Kei; Ichikawa, Satoshi; Fujiwara, Tohru; Fukuhara, Noriko; Harigae, Hideo

doi:10.1007/s00277-019-03645-7

Cited by 15 publications

(12 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 42 Atypical infections are uncommon, however, reactivation of herpes zoster and Epstein–Barr virus/cytomegalovirus, pneumocystis jirovecii pneumonia (PJP), progressive multifocal leukoencephalopathy, bronchopulmonary aspergillosis, fungal meningitis, listeriosis, and disseminated cryptococcosis are reported. 43 – 50 As expected, infections occur at a higher rate in those patients with higher grade neutropenia and lymphopenia, notably heavily pretreated patients treated with combination regimens within the initial 6 months of treatment. In this population treated with daratumumab, the median time to severe infection was ~50 days in patients with severe lymphopenia versus ~90 days in those without severe lymphopenia.…”

Section: Fda-approved Next-generation Therapeuticssupporting

confidence: 59%

Toxicity management strategies for next-generation novel therapeutics in multiple myeloma

Steinbach

Julian

McClune

et al. 2022

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

The therapeutic options available for patients with multiple myeloma have greatly expanded over the past decade and incorporating these novel agents into routine clinical practice has significantly improved outcomes. The next generation of therapeutics is available for relapsed and refractory patients either as standard of care or in clinical trial, and these drugs represent a generational paradigm shift. Patients now have access to a multitude of novel immunotherapeutics, including monoclonal antibodies, an antibody–drug conjugate, chimeric antigen receptor T-cells (CAR-T), and bispecific T-cell redirecting antibodies, and novel oral therapies including selinexor (selective inhibitor of nuclear export) and venetoclax (bcl-2 inhibitor). While these drugs have the potential to be highly efficacious in certain subsets of patients when used as single agents or in combination regimens, they are each associated with unique toxicity profiles. It is imperative to understand these potential adverse events to ensure patient safety. Appropriate supportive care management is paramount to maximize drug exposure and therapeutic efficacy. The following review focuses its discussion on drugs and combination regimens that are currently FDA-approved and those that continue to be investigated in clinical trials, highlights the clinically relevant toxicity profiles for each of the different agents, and provides practical considerations for the treatment team.

show abstract

Section: Fda-approved Next-generation Therapeuticssupporting

confidence: 59%

Toxicity management strategies for next-generation novel therapeutics in multiple myeloma

Steinbach

Julian

McClune

et al. 2022

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

show abstract

“…The mechanism of action of daratumumab is based on the elimination of tumor cells expressing high levels of CD38 through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Recent studies have reported an increased risk of infection in multiple myeloma patients undergoing treatment with daratumumab, either as monotherapy or as combined therapy with other drugs, with some cases resulting in lethal sepsis [87][88][89][90][91][92][93]. Infections reported as drug-related adverse effects include opportunistic bacterial infections of the respiratory or urinary tracts (e.g., S. pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Haemophilus influenzae), exogenous viral infections (e.g., acute respiratory syncytial virus, human metapneumovirus and influenza A and B viruses) and viral reactivations (e.g., cytomegalovirus, herpes simplex virus and varicella-zoster virus).…”

Section: Increased Risk Of Infections In Immunotherapies Using Anti-cmentioning

confidence: 99%

Roles of CD38 in the Immune Response to Infection

Glaría

Valledor

2020

Cells

View full text Add to dashboard Cite

CD38 is a multifunctional protein widely expressed in cells from the immune system and as a soluble form in biological fluids. CD38 expression is up-regulated by an array of inflammatory mediators, and it is frequently used as a cell activation marker. Studies in animal models indicate that CD38 functional expression confers protection against infection by several bacterial and parasitic pathogens. In addition, infectious complications are associated with anti-CD38 immunotherapy. Although CD38 displays receptor and enzymatic activities that contribute to the establishment of an effective immune response, recent work raises the possibility that CD38 might also enhance the immunosuppressive potential of regulatory leukocytes. This review integrates the current knowledge on the diversity of functions mediated by CD38 in the host defense to infection.

show abstract

“…Ongoing phase I-II trials have been designed in RR-MM patients with the combination of DARA and the anti-PD-1 mAbs, pembrolizumab [99], nivolumab (NCT03184194, NCT01592370) or the anti-PD-L1, durvalumab (FUSION-MM-005) and atezolizumab (NCT02431208). Interestingly, preliminary results from FUSION-MM-005 revealed a low rate of viral reactivation (1 out of 18 patients) as compared to other trials using DARA in monotherapy, which displayed cytomegalovirus and herpes zoster reactivation, mainly due to NK cell depletion [100,101]. These results may suggest that the combination of anti PD-L1/PD-1 mAbs with CD38 blocking Abs could display less toxicity due to infections as compared with the combination with IMiDs; however, only the availability of more data from the ongoing clinical trials could clarify this aspect.…”

Section: The Possible Link Between Cd38 and Pd-l1 In MMmentioning

confidence: 86%

PD-L1/PD-1 Axis in Multiple Myeloma Microenvironment and a Possible Link with CD38-Mediated Immune-Suppression

Costa

Marchica

Storti

et al. 2021

Cancers

View full text Add to dashboard Cite

The emerging role of the PD-1/PD-L1 axis in MM immune-microenvironment has been highlighted by several studies. However, discordant data have been reported on PD-1/PD-L1 distribution within the bone marrow (BM) microenvironment of patients with monoclonal gammopathies. In addition, the efficacy of PD-1/PD-L1 blockade as a therapeutic strategy to reverse myeloma immune suppression and inhibit myeloma cell survival still remains unknown. Recent data suggest that, among the potential mechanisms behind the lack of responsiveness or resistance to anti-PD-L1/PD-1 antibodies, the CD38 metabolic pathways involving the immune-suppressive factor, adenosine, could play an important role. This review summarizes the available data on PD-1/PD-L1 expression in patients with MM, reporting the main mechanisms of regulation of PD-1/PD-L1 axis. The possible link between the CD38 and PD-1/PD-L1 pathways is also reported, highlighting the rationale for the potential use of a combined therapeutic approach with CD38 blocking agents and anti-PD-1/PD-L1 antibodies in order to improve their anti-tumoral effect in MM patients.

show abstract

Preemptive therapy for cytomegalovirus reactivation after daratumumab-containing treatment in patients with relapsed and refractory multiple myeloma

Cited by 15 publications

References 9 publications

Toxicity management strategies for next-generation novel therapeutics in multiple myeloma

Toxicity management strategies for next-generation novel therapeutics in multiple myeloma

Roles of CD38 in the Immune Response to Infection

PD-L1/PD-1 Axis in Multiple Myeloma Microenvironment and a Possible Link with CD38-Mediated Immune-Suppression

Contact Info

Product

Resources

About