Latent tuberculosis infection detected by quantiferon-TB assay in patients with multiple myeloma receiving novel drugs: focus on reactivation prophylaxis in a retrospective, single-center study

Excerpt

Patients with immunodeficiencies have a greater risk of progressing to active tuberculosis (TB) once infected and this risk, in patients with hematologic malignancies, is 2–40 times higher compared to the general population [1]. Consequently, according to current recommendations [2‐4], it is important to diagnose latent TB infection in these immunodeficient patients and to consider an appropriate prophylaxis to avoid a possible disease reactivation leading to active TB. Regarding this aspect however, only limited data is available in the setting of patients with multiple myeloma (MM) treated with novel drugs (proteasome inhibitors, IMiDs and monoclonal antibodies) [5‐8]. Therefore, we retrospectively evaluated the incidence of latent TB infection by the LIAISON® QuantiFERON®-TB Gold Plus (QFT-Plus) assay, in 180 consecutive patients with active MM observed at our Institution since January, 2020, to June, 2023. This method, characterized by high specificity (95%) and sensitivity (91%) [9] if compared to skin test (specificity: 62% - BCG vaccinated / 95% BCG unvaccinated; sensitivity: 75%) [10] and chest radiographic features (median specificity: 46%; sensitivity: median 96%) [11], detects interferon-γ produced by T-lymphocytes following the stimulation by specific antigens of Mycobacterium tuberculosis complex; in particular LIAISON QFT-Plus is based upon a chemiluminescent immunoassay (CLIA) sandwich assay developed by DiaSorin (Saluggia, Italy) on the Liaison XL platform to determine IFN-γ [9, 12]. The test was performed together with other preliminary blood tests, including viral hepatic markers and HIV at diagnosis or at disease progression, before starting treatment. LIAISON® QFT-Plus was found positive in 26 subjects (14.4%), of which only three patients were foreign born. No patient reported a history of TB vaccination. The patient’s clinical characteristics are summarized in Table 1. The median age was 75 years (range: 42–83), with a male predominance (53.9%). In twenty-two patients (84.6%) the test was positive before starting first line of treatment; in 4 patients (15.4%), it was assessed and found positive at the time of first progression of MM. Twenty-one (80.8%) patients with a latent TB received prophylactic treatment (isoniazid or rifampicin) prescribed by the infectious disease specialist according to current WHO guidelines [2‐4], while 5 did not (two patients had been treated for active TB several years before; three patients were excluded from prophylaxis due to poor kidney function and/or other important comorbidities). Fourteen patients (66.7%) received isoniazid, at standard dose of 300 mg/day in combination with pyridoxine supplementation for six months, while 7 patients received a monotherapy of rifampicin 600 mg/day for 4 months. In one patient, isoniazid was stopped due to liver toxicity. Eleven patients (HBsAg negative, anti-HBs positive, total anti-HBc positive, HBV-DNA negative) were also healthy hepatitis B virus carriers and needed concomitant lamivudine as prophylaxis to prevent HBV reactivation [13]. Regarding specific treatments for MM, all patients included in this analysis received novel drugs, such as proteosome inhibitors, IMiDs and monoclonal antibodies; four of them underwent autologous hematopoietic stem cell transplant too. With a median time of observation of 715 days (range: 196–2640), none of the patients developed TB reactivation during or after MM treatment with novel drugs. Moreover, TB prophylaxis was not associated with any significant toxicity in all but one cases. In conclusion, TB screening using QFT-Plus test before starting treatment, allows to reveal a not negligible proportion of MM patients with latent TB infection and this appears to be particularly important for bispecific antibodies and CAR-T cell therapy, characterized by high incidence of infectious complications. Specific prophylaxis in these subjects was generally safe (including those also receiving lamivudine) and could have been avoided possible reactivations of latent TB. …