Nicola Sgherza

Summary: The extensive use of lenalidomide (Len) in the first‐line treatment of multiple myeloma (MM) has resulted in an increased frequency of patients who have been exposed or are refractory to Len (Len‐R) at first relapse. However, the outcome of Len‐R patients treated at first relapse after autologous haematopoietic stem cell transplantation (AHSCT) remains unclear. The aim of this real‐life study is to evaluate the effectiveness of the regimens licensed in Italy and used in a cohort of patients who relapsed during Len maintenance after AHSCT. We collected 306 patients with these features. Considering the different regimens used, most patients received isatuximab–carfilzomib–dexamethasone (Isa‐KD) (45.4%) followed by daratumumab–pomalidomide–dexamethasone (D‐PD) (19.3%) and daratumumab–bortezomib–dexamethasone (D‐VD) (12.4%). Overall, a reduced progression‐free survival (PFS) and overall survival (OS) were observed in patients with high‐risk disease features at relapse, including high lactate dehydrogenase (LDH) ( p = 0.0003 and p < 0.0001), International Staging System (ISS) ≥2 ( p < 0.0001 and p < 0.0001) and early relapse (p = 0.0017 and p = 0.0009). Considering the type of treatment, anti‐cluster of differentiation 38 (CD38) monoclonal antibodies (anti‐CD38 MoAb)‐based regimen displayed improved survival compared to the other treatment, with Isa‐KD reporting the longest PFS (22.8 months). Our data in a homogenous cohort of Len‐R patients treated at first relapse demonstrated that the anti‐CD38 MoAb‐based combinations, particularly Isa‐KD, represented the standard of care before the approval of anti‐B cell maturation antigen (BCMA) immunotherapy.

Background: Human metapneumovirus (hMPV) is an increasingly recognized respiratory pathogen in immunocompromised patients, but its impact in haematological malignancies is poorly defined. Unlike influenza or SARS-CoV-2, hMPV has no specific treatment or vaccine, contributing to underdiagnosis and underestimation of its clinical relevance. Method: We performed a multicentre retrospective cohort study within the Epidemiology of COVID-19 in patients with hematological malignancies: A European Haematology Association Survey/ Epidemiology of respiratory viral infections in patients with hematological malignancies: A European Haematology Association Survey registry of haematological patients with hMPV (January 2023–December 2024), comparing clinical features and outcomes with matched influenza and SARS-CoV-2 cohorts. Results: The study included 130 patients with hMPV. Median age was 58.5 years; 57% were male. Plasma cell neoplasms (25%), lymphoma (23%), and acute myeloid leukemia (20%) were the most common hematological malignancies. Hospitalization occurred in 64%, intensive care unit (ICU) admission in 19%, and 30-day mortality was 8%. Most cases (73%) received supportive care only. Secondary infections were common (24%). Chronic renal disease significantly increased mortality risk (hazard ratio 20.9 11.05, P = .014). Compared with influenza and SARS-CoV-2, hMPV patients had comparable severity and outcomes, with 18.5% ICU admission rates versus 25.9% for influenza (P = .316) and 20.9% versus 4.7% for SARS-CoV-2 (P = .006), and 30-day mortality of 5.6% versus 11.1% for influenza (P = .489) and 7.0% versus 2.3% for SARS-CoV-2 (P = .277), yet received fewer targeted interventions. Conclusions: hMPV causes clinically significant disease in patients with hematological malignancy, often necessitating hospital and ICU care, and leading to mortality. In the absence of specific treatments or vaccines, this virus remains an underrecognized pathogen in patients with hematological malignancy. Enhanced clinical awareness and investment in diagnostics, prevention, and therapeutics are needed.

Background: In the randomized, phase-3 IKEMA trial, the triplet isatuximab, carfilzomib, and dexamethasone (IsaKd) demonstrated superior clinical benefit compared to those of carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma after 1–3 prior treatments. Methods: Our real-world, AENEID study aimed to evaluate the efficacy and safety of IsaKd in patients who relapsed after frontline lenalidomide treatment, poorly represented in the IKEMA trial. Specifically, in the present multicenter analysis, we enrolled eighty-two patients who received, between April 2022 and September 2024 and outside of clinical trials, at least one cycle of IsaKd as a second-line treatment at the first relapse after induction therapy, autologous stem cell transplantation (ASCT), and lenalidomide maintenance. Results: After a median follow-up time of 12.9 months (range, 1–77), the overall response rate, at least a very good partial response rate, and median progression-free survival time were 79.3%, 56.1%, and 24.4 months, respectively. This slightly lower performance compared to that in the IKEMA study may be attributed to the well-known poor prognostic impact of lenalidomide refractoriness (len-R), developed by all our patients during maintenance therapy, and to a higher proportion of patients with extramedullary disease present in our series, which was identified as the only factor significantly affecting the PFS in multivariable analysis. The median overall survival was not reached, as in the pivotal trial, while the 1-year survival probability was 85.1%. Regarding the safety profile, our findings were consistent with those of the IKEMA trial, with no new safety signals reported. Conclusions: These real-world data support the use of IsaKd as a valuable option for len-R MM patients relapsing after the first-line therapy, including ASCT and lenalidomide maintenance.

Relapsed/refractory multiple myeloma (RRMM) research on the impact of +1q abnormalities in real‐world settings is limited. This study evaluated the prognostic and predictive significance of 1q gain [gain(1q)] and amplification [ampl(1q)] in 635 RRMM patients treated with daratumumab‐, elotuzumab‐, and carfilzomib‐based triplet regimens. Patients with +1q abnormalities had lower deep response rates [≥ CR: 9.4% for gain(1q), 11.6% for ampl(1q)] versus 20.2% in +1q‐negative patients. Multivariable ordinal logistic analysis showed significantly lower odds of achieving ≥ CR in patients with gain(1q) (OR = 0.49, p < 0.001) or ampl(1q) (OR = 0.58, p = 0.0037). Progression‐free survival (PFS) was longer in +1q‐negative patients (28 months) compared to those with gain(1q) (8 months) or ampl(1q) (7.4 months). Multivariable models identified gain(1q) (HR = 1.9, p < 0.001) and ampl(1q) (HR = 2.2, p < 0.001) as independent negative prognostic factors alongside del17p, t(4;14), creatinine clearance < 60 mL/min, and ISS Stages II and III. Similarly, overall survival (OS) was reduced for patients with gain(1q) (25 months) and ampl(1q) (19.5 months) versus 42.2 months in +1q‐negative patients. Multivariable analysis showed gain(1q) (HR = 1.6, p = 0.007) and ampl(1q) (HR = 2.0, p = 0.002) as independent predictors of increased mortality. Ancillary +1q abnormalities associated with high‐risk cytogenetic changes were linked to both shorter PFS and OS. Stratification into no‐hit, single‐hit, double‐hit, and triple‐hit groups showed significant survival differences, emphasizing the impact of cumulative cytogenetic abnormalities on outcomes. In conclusion, +1q abnormalities significantly impact prognosis in RRMM and should be considered in risk stratification. The study emphasizes the importance of comprehensive cytogenetic profiling in real‐world settings and highlights the need for personalized treatment strategies to improve patient outcomes.

Community‐acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large‐scale, real‐world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA‐EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023–2024 autumn–winter season. The study assessed epidemiology, clinical characteristics, risk factors, and outcomes. The study examined 1312 patients with HM diagnosed with CARV during the 2023–2024 autumn–winter season. Of these, 59.5% required hospitalization, with 13.5% needing ICU admission. The overall mortality rate was 10.6%, varying by virus: parainfluenza (21.3%), influenza (8.8%), metapneumovirus (7.1%), RSV (5.9%), or SARS‐CoV‐2 (5.0%). Poor outcomes were significantly associated with smoking history, severe lymphopenia, secondary bacterial infections, and ICU admission. This study highlights the severe risk CARV poses to patients with HM, especially those undergoing active treatment. The high rates of hospitalization and mortality stress the need for better prevention, early diagnosis, and targeted therapies. Given the severe outcomes with certain viruses like parainfluenza, tailored strategies are crucial to improving patient outcomes in future CARV seasons.