(PA-402) Incidence and Timing of Infections in Patients with Newly Diagnosed Myeloma Treated with Contemporary Regimens

Patients with multiple myeloma are at high risk for infections due to their compromised immune system, other co-morbidities and treatment-related factors. Understanding this risk of infections in patients treated with contemporary regimens in the real world setting is important to develop preventive and management strategies.

Methods:

To evaluate risk and incidence of infections in newly diagnosed myeloma (NDMM) patients we analyzed the infectious complications (i.e infections of at least grade 3) in newly diagnosed consecutive myeloma patients, treated in a single center (Department of Clinical Therapeutics, Athens).

The analysis included 539 patients, that started treatment between 1/1/2020 and 31/12/2024, thus including patients from the start of COVID period.

Results:

Median age was 67 years; 56% were >65 years,  54% were males. Per ISS, 34%, 36% and 30% were stage 1, 2 & 3 respectively, 21% had high risk cytogenetics, 16% had eGFR< 30 ml/min/1.73 m2 and 4% required dialysis at the time of diagnosis. Treatment included a PI in 78%, lenalidomide in 77%, PI+lenalidomide in 56% (VRd in 33%) and anti-CD38 in 38% (Daratumumab-VRd in 18%).  The median follow-up of the cohort is 2.5 years and 20% of the patients have died.

During their first line therapy 26% of the patients had at least one grade≥3 infection. The rates of infection were higher in the first 3-6 months from start of treatment; the rate of grade ≥3 infections at 3, 6, 12 and 18 months was 10%, 15%, 16% and 19% respectively.  Lower respiratory tract infections (grade ≥3) were the most common (in 64 (12%) of all patients) and grade ≥3 COVID-19 in 35 (6.5%); the cause of death was mainly infectious in 32 patients (6%).

Factors associated with higher risk of infections during the first 6 months from start of treatment included ECOG PS≥2 (p=0.002), eGFR (p=0.003), increased serum LDH ( >ULN) (p=0.045). The use of anti-CD38-based induction regimens was associated with a numerically higher risk of infections (vs non-anti-CD38) at 6 months (18% vs 15%, p=0.396) or at 12 months (22% vs 17%, p=0.183); however, focusing on patients treated with Dara-VRd vs VRd, the addition of daratumumab to VRd was associated with significantly higher rates of Grade³3 infections at 6 months (21% vs 13%, p=0.067) and at 12 months (26% vs 15%, p=0.023).
Based on the results of multivariate analysis we developed a risk score with 1 point for eGFR< 30 ml/min/1.73 m2 and LDH >ULN and 2 points for ECOG PS≥2: the 6, 12 and 18 months Grade≥3 infection rate at 6 months was 9%, 19% and 30%, at 12 months was   13%, 23%, 33% and at 18 months was 16%, 26% and 40% for the three risk groups respectively (p< 0.001). 

Conclusions:

In conclusion, in this real-world contemporary cohort, infectious complication are frequent and their burden is higher during the first 3 months from the start of therapy. Use of anti-CD38 antibodies further increases this risk. Strategies to reduce infectious complications should be implemented in routine clinical care.