Severe cytomegalovirus enterocolitis developing following daratumumab exposure in three patients with multiple myeloma

Abstract

Novel myeloma treatments prolong patient survival and more patients with profound immunosuppression following multiple lines of therapies are seen in clinical practice. These patients may present with opportunistic infections that were rare in the past. Our findings suggest a possible association between daratumumab therapy (in combination with other immunosuppressive therapies) and severe CMV gastrointestinal disease. A longer follow-up is needed to explore long-term side effects of novel agents like daratumumab in newly diagnosed as well as heavily pretreated MM patients.

Daratumumab in multiple myeloma

“…Interestingly, the absolute CD56+ lymphocytes (NK cells) were severely diminished among patients receiving daratumumab, and the median CD56+ lymphocytes were Cancer July 15, 2019 significantly lower among patients who had an infection in comparison with patients without an infection. 38 Several other groups have reported similar findings of increased susceptibility to infectious complications of cytomegalovirus 39 and fungal and parasitic infections 38 among patients with myeloma receiving daratumumab.…”

“…Interestingly, the absolute CD56+ lymphocytes (NK cells) were severely diminished among patients receiving daratumumab, and the median CD56+ lymphocytes were significantly lower among patients who had an infection in comparison with patients without an infection . Several other groups have reported similar findings of increased susceptibility to infectious complications of cytomegalovirus and fungal and parasitic infections among patients with myeloma receiving daratumumab. A recently published meta‐analysis designed to determine the risks of upper respiratory tract infections and pneumonia in patients with myeloma reported a pooled risk ratio for an upper respiratory tract infection of 1.59 (95% CI, 1.33‐1.91; P = .00001) and a pooled risk ratio for pneumonia of 1.48 (95% CI, 1.14‐1.93; P = .002) among patients receiving daratumumab .…”

Hepatitis B virus reactivation in a myeloma patient with resolved infection who received daratumumab-containing salvage chemotherapy

“…DARA is an IgG1 kappa monoclonal antibody targeting CD38 that that is expressed not only in myeloma cells, but also in non-malignant T cells, natural killer (NK) cells, B cells, and plasma cells. 13,14 Recently, DARA-containing chemotherapy was reported to be associated with CMV infection, 3,4,6 suggesting that cellular immunity was suppressed in some patients who received DARA-containing chemotherapy. More recently, a retrospective study assessing circulating lymphocytes revealed that DARA can selectively deplete NK cells, which may lead to viral reactivation.…”

“…2 However, DARA treatment may be associated with an increased risk of viral infection; specifically, cytomegalovirus (CMV) reactivation occurs in patients with multiple myeloma after DARA administration. [3][4][5][6] Hepatitis B virus (HBV) reactivation is also a potentially fatal complication of DARA treatment. 7,8 Rituximab, an anti-CD20 monoclonal antibody, plus steroid combination chemotherapy is a risk factor in patients with resolved HBV infection, defined as being seronegative for hepatitis B surface antigen (HBsAg), but seropositive for antibodies against hepatitis B core antigen (anti-HBc) and/or antibodies against HBsAg (anti-HBs).…”

Accompanying therapy in oncohematological patients with secondary immunodeficiency

“…В недавнем ретроспективном исследовании частота инфекций, обусловленных цитомегаловирусом, во время лечения ММ, главным образом с применением бортезомиба, достигла 11% [9]. Описаны случаи развития цитомегаловирусного энтероколита при лечении анти-CD38-моноклональным антителом даратумумабом, однако зачастую даратумумаб назначался в составе комбинированной терапии, включающей ингибиторы протеасом (карфилзомиб, бортезомиб), поэтому не исключено, что осложнения могут быть связаны с одним из других препаратов комбинации [10].…”