Practical Considerations for the Daratumumab Management in Portuguese Routine Clinical Practice: Recommendations From an Expert Panel of Hematologists

Abstract

The recent therapeutic progress in multiple myeloma (MM) has led to the introduction of novel and highly potent drug classes. Daratumumab was the first CD38-targeting antibody showing to be effective and safe in MM patients as monotherapy and in combination regimens, which led to its rapid implementation in clinical practice. Considering that treatment discontinuation for drug-related adverse events can impact patients’ quality of life and outcomes, the treatment decision should consider different factors and be weighted for each patient individually. Here, we aimed to guide clinicians using daratumumab treatment for MM by addressing practical real-world considerations based on an expert panel of Portuguese hematologists. Carefully following the recommendations mentioned in daratumumab’s SmPC, and of those from other drugs used in combination regimens, along with ensuring a good communication with all healthcare professionals involved, is critical to prevent any complications arising from treatment. The risk of infection should be assessed for all patients under treatment with daratumumab and patients should be educated on the potential adverse events. Recommendations on prophylaxis and vaccination should be considered to avoid infections, and delays in the planned therapeutic schedule may be required to prevent adverse consequences of hematological toxicity. Daratumumab treatment is effective and feasible in patients with renal impairment, although careful patient monitoring and a frequent communication with the Nephrology department are of the utmost importance. Sharing clinical practice plays an important role in medical education by allowing to maximize treatment efficacy and minimize its safety risks.

Daratumumab in post-transplantation pure red cell aplasia in adults

“…One should also note a low toxicity profile of daratumumab known from clinical experience with multiple myeloma patients. However, there is a high risk of developing infectious complications [25][26][27]. Currently, there is insufficient data on the use of daratumumab after allo-HSCT and assessing its effect on GvHD [28, 29].…”

Cytomegalovirus reactivation is frequent in multiple myeloma patients treated with daratumumab‐based regimens

“…A high incidence of infections (overall transversal risk, 38%), especially upper respiratory tract infections and pneumonia, has been reported in several daratumumab trials, 13 because of its immunosuppressive actions, including secondary hypogammaglobulinemia, depletion of regulatory B/T lymphocytes and natural killer (NK) cells, and neutropenia. 28 , 29 , 30 , 31 , 32 Although the risk of bacterial infections and hepatitis virus or HZV reactivation has been clearly assessed, few data are available on CMV reactivation risk, without a clear recommendation for anti‐CMV prophylaxis.…”

“… 28 , 29 , 30 , 31 , 32 Although the risk of bacterial infections and hepatitis virus or HZV reactivation has been clearly assessed, few data are available on CMV reactivation risk, without a clear recommendation for anti‐CMV prophylaxis. 13 , 17 In this single‐center, two‐arm, retrospective, real‐life study, we investigated the CMV reactivation rate in MM patients treated with the anti‐CD38 monoclonal antibody daratumumab as first‐ or second‐line therapy, and outcomes were compared to a daratumumab‐naïve control group.…”

“… 11 In clinical trials, the overall infectious risk under daratumumab treatment is estimated ~38% across different studies, for both newly‐diagnosed and RR MM, with bacterial pneumonia as the most common infectious complication, leading to treatment discontinuation in 1%–4% of cases. 12 , 13 Daratumumab‐induced immunosuppression is also associated with an increased risk of viral reactivation, including Hepatitis B virus, Hepatitis C virus, and Herpes Zoster virus, leading to treatment delays, interruptions, or discontinuation. 12 …”

“…11 In clinical trials, the overall infectious risk under daratumumab treatment is estimated ~38% across different studies, for both newly-diagnosed and RR MM, with bacterial pneumonia as the most common infectious complication, leading to treatment discontinuation in 1%-4% of cases. 12,13 Daratumumab-induced immunosuppression is also associated with an increased risk of viral reactivation, including Hepatitis B virus, Hepatitis C virus, and Herpes Zoster virus, leading to treatment delays, interruptions, or discontinuation. 12 Cytomegalovirus (CMV) is a common pathogen with a prevalence of 83% in general population, and clinical manifestations vary from asymptomatic in healthy people to severe end-organ dysfunction in immunocompromised subjects, including hematological patients and posttransplant recipients.…”