Clinical Lymphoma, Myeloma & Leukemia最新文献

Ibrutinib, a Bruton tyrosine kinase inhibitor, is a cornerstone of first-line treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). While generally well tolerated, dose adjustments may be used in some patients to manage adverse events or tolerability issues. This review examines the real-world outcomes such as the effectiveness and duration of therapy of first-line ibrutinib treatment in patients with CLL/SLL, including those with high-risk genomic features. The role of flexible dosing strategies, including dose adjustments or interruptions, and their role in optimizing ibrutinib treatment duration and outcomes are explored. Consistent with results from clinical trials, real-world evidence supports the effectiveness of ibrutinib dosing flexibility in managing adverse events while maintaining long-term clinical benefits. Ibrutinib dose adjustments help optimize treatment persistence and reduce treatment discontinuations, thereby enabling continuous ibrutinib treatment. Furthermore, real-world evidence suggests that ibrutinib dose flexibility contributes to reduced healthcare resource utilization, including fewer hospitalizations and outpatient visits, thus lowering the economic burden of CLL/SLL treatment. Long-term effectiveness, together with lower costs and the ability to tailor ibrutinib dosing to individual patients, supports ibrutinib as a pivotal agent in the management of CLL/SLL.

Background: High dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) remains the preferred consolidation strategy for patients with newly diagnosed multiple myeloma (MM). While its use has expanded to patients over 65 years (> 65), few studies have compared real-world outcomes to younger patients.

Patients and methods: This retrospective cohort study included patients with MM who received first line HDT/ASCT between 2013 and 2022 at a large tertiary referral center in The Netherlands. We compared outcomes between patients > 65 years and 65 years or younger (≤ 65), assessing overall survival (OS), time to next treatment or MM-related death (TTNT-D), complications, and quality of life.

Results: Among 394 patients, 109 were > 65 years (range 66-72, 11 patients > 70) and 285 ≤ 65 years (range 34-65). Distributions in baseline characteristics were comparable. Median OS and TTNT-D were 101 and 41 months, respectively, in patients > 65 years compared to 116 (P = .56) and 38 (P = .78) months for patients ≤ 65 years. Age was not a significant predictor. HDT/ASCT was feasible, illustrated by a low serious complications incidence rate and a transplantation-related mortality of 1%. Quality of life data show a stable to increasing trend in the long term.

Conclusion: Survival, treatment response, complication rates, and long-term quality of life were comparable between age groups. Our real-world data confirm the safety and efficacy of HDT/ASCT in fit patients with MM over 65 years. These findings support the broader application of HDT/ASCT in selected older patients and reinforce its role.

Background: The International Myeloma Society/International Myeloma Working Group (IMS-IMWG) recently redefined high-risk multiple myeloma (MM), specifying that gain(1q) confers high risk only when co-occurring with monoallelic del(1p), whilst immunoglobulin heavy chain (IgH) translocations (t[4;14], t[14;16], t[14;20]) are considered high risk only when accompanied by gain(1q) or del(1p).

Methods: Data from 5927 newly diagnosed MM (NDMM) patients in the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) were analyzed. Fluorescence in situ hybridization (FISH) data were available for 3397 (57%) patients. High-risk cytogenetic abnormalities (HRCA) included t(4;14), t(14;16), del(17p), and gain(1q). Clinical characteristics and outcomes were compared by the number of HRCA present.

Results: Patients with multiple HRCA more frequently presented with anemia, thrombocytopenia, hypercalcemia, greater bone marrow plasma cell burden, elevated lactate dehydrogenase, higher β2-microglobulin levels, and IgA paraprotein secretion. Increasing HRCA burden was associated with significantly shorter progression-free survival (PFS) and overall survival (OS). Although overall response rates to first-line therapies were similar across groups, the duration of response declined with increasing HRCA number. Each HRCA independently conferred poorer outcomes compared with no HRCA, with del(17p) associated with the shortest PFS and OS. The addition of another HRCA did not significantly alter outcomes in del(17p) patients.

Conclusion: The cumulative burden of high-risk cytogenetic abnormalities predicts inferior survival in NDMM, underscoring the need for refined risk stratification and tailored therapeutic strategies.

Introduction: Waldenström macroglobulinemia (WM) is a rare, slow-growing B-cell lymphoma characterized by the proliferation of lymphoplasmacytic cells in the bone marrow. WM has been difficult to diagnose and treat. However, recent advances in diagnostics, including the discovery of MYD88 and CXCR4 mutations, and in treatment, including targeted, patient-tolerable therapeutic options in often elderly patients, have together improved the clinical outcomes.

Methods: In this nationwide retrospective real-world evidence (RWE) study, we report the incidence, prevalence, patient characteristics, comorbidities, overall survival, causes of deaths and healthcare resource utilization (HCRU) of all Finnish patients diagnosed with WM during 2007-2021.

Results: The mean incidence was 0.49, age standardized incidence 0.23 and prevalence (in 2021) 3.7 per 100,000 people. The median overall survival (mOS) for all WM patients during the entire study period was 7.3 years. An improvement in the OS was observed over time (2007-2014 vs. 2015-2021 cohorts). Infections along with WM itself were a major cause of death among WM patients.

Conclusions: To our knowledge, this is the first RWE study of WM patients in Finland.

Background: High-dose chemotherapy with melphalan (HDCT) and autologous stem cell transplantation (ASCT) represents a gold standard treatment for younger multiple myeloma (MM) patients (<70 years). The benefit of upfront HDCT/ASCT in elderly patients (≥70 years) remains undefined. This analysis investigated survival outcomes among both age groups undergoing front-line HDCT/ASCT.

Methods: This retrospective analysis included MM patients treated between February 1998 and November 2023 at 2 German university hospitals. Patients were divided into age groups (<70 vs. ≥70), and further categorized whether they received HDCT/ASCT or not. Treatment outcomes, progression-free survival (PFS), and overall survival (OS) were compared using Kaplan-Meier analysis and Cox regression.

Results: Of 517 patients (395 patients <70 years; 122 patients ≥70 years), 343 (66.3%) patients underwent HDCT/ASCT (307 patients <70 years, 89.5% of eligible patients; 36 patients ≥70 years, 10.5% of eligible patients). The remaining 174 (33.7%) patients did not receive HDCT/ASCT (88 patients <70 years; 86 patients ≥70 years). HDCT/ASCT significantly improved both PFS and OS in all patients. Elderly recipients demonstrated longer PFS than younger recipients (10.27 vs. 2.74 years; P = .006), likely due to more frequent use of anti-CD38 antibody-based induction and maintenance therapy. OS was significantly longer in younger recipients (17.31 vs. 4.87 years; P = .003). In the multivariate analysis, HDCT/ASCT remained a strong protective factor for both PFS and OS.

Conclusion: HDCT/ASCT confers a significant survival benefit in both younger and selected elderly MM patients. Advanced age alone should not exclude HDCT/ASCT; therefore, transplant-eligibility should be determined by comprehensive assessment of functional status and comorbidities.

Background: Central nervous system involvement in multiple myeloma (CNS-MM) is a rare but aggressive extramedullary manifestation occurring in approximately 1% of multiple myeloma (MM) patients. CNS-MM is associated with poor prognosis, with median survival ranging from 2 to 7 months. Small studies have suggested that advances in MM treatment may be leading to increasing prevalence of CNS-MM; however, a comprehensive analysis of temporal trends is lacking.

Methods: We conducted an epidemiological study of the 2012-2020 National Inpatient Sample, an all-payer database of US inpatient hospital admissions. Patients aged 18 and older with both MM and secondary CNS neoplasms were identified using ICD-9 and ICD-10 diagnosis codes. We then calculated weighted prevalence estimates and assessed them using regression analysis.

Results: CNS-MM prevalence increased significantly, increasing by 166% from 2012 to 2020 (P < .001). This increase outpaced the 29% rise in overall MM prevalence (P < .001) during the same period. We observed no significant changes in mortality or discharge outcomes over time. Patients who were white (P < .05) and had income over median (P < .01) received more CNS-targeting diagnostic or therapeutic care, but we found no evidence of improved inpatient survival due to these procedures (P = .70) after adjusting for disease severity.

Conclusion: The prevalence of CNS-MM has grown to 2%-3% of MM patients since 2020, with stable rates of mortality despite interventions. Further investigation is needed to explore underlying mechanisms of this growth and improve outcomes.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype non-Hodgkin lymphoma. HIV, hepatitis B (HBV), and hepatitis C (HCV) infections are DLBCL risk factors. DLBCL remains a leading cause of cancer-related morbidity and mortality in those with HIV. DLBCL treatments can also increase the HBV reactivation risk and acute liver injury in HCV. We assessed HBV, HCV, and HIV screening rates in DLBCL patients receiving systemic therapy in a comprehensive cancer system.

Materials and methods: We analyzed newly diagnosed DLBCL patients receiving anti-CD20 therapies between January 2018 and December 2023. Patients were considered screened if they had viral testing or a prior diagnosis within 12 months before to 3 months after starting treatment. We used chi-squared and Fisher's exact tests to examine associations between patients who were and were not screened HBV, HCV, and HIV. We used univariate and multivariate logistic regression to identify the factors associated with screening.

Results: A total of 535 patients with DLBCL were treated (median age 64, 42% female, 82% white). Among these patients, 410 (77%) had HBV testing or a known infection, 275 (51.4%) had HIV testing or a known infection, and 307 (53%) had HCV testing or a known infection. Younger people were more likely to be tested for HIV and HCV. There was no association between age and HBV testing.

Conclusion: Pre-treatment HIV, HBV, and HCV screening rates in newly diagnosed DLBCL patients remains suboptimal. Interventions to increase viral testing in this population could help reduce treatment-related morbidity and mortality.

The global incidence of multiple myeloma (MM) continues to rise. While survival rates for newly diagnosed patients have improved substantially with the introduction of novel therapies, outcomes remain poor for those with triple-class-exposed (TCE) relapsed/refractory MM (RRMM). Recent therapeutic innovations, including chimeric antigen receptor T-cell therapy, antibody-drug conjugates, and bispecific antibodies, offer new effective options for this challenging population. Teclistamab, the first approved B-cell maturation antigen-targeted bispecific antibody, has demonstrated deep and durable responses and an acceptable safety profile in TCE RRMM. Teclistamab is now a recommended treatment from second relapse onwards in patients with TCE RRMM in the 2025 European Hematology Association-European Myeloma Network guidelines. Nevertheless, considering the novelty of this agent and its overall safety profile, there is a need for clear guidance on patient management in routine clinical practice. Here, we aim to provide a comprehensive overview of the clinical profile of teclistamab and expert recommendations on its optimal use in TCE RRMM. We focus on key aspects and considerations needed for patient selection (including special populations such as the elderly, frail individuals, those with extramedullary disease or renal impairment), as well as therapy initiation, and strategies for adverse event prevention, monitoring, and management. Ultimately, this review aims to support physicians in maximizing the therapeutic potential of teclistamab, improving outcomes for patients through tailored, evidence-based management.

Background: Targeted therapies have replaced chemoimmunotherapy for chronic lymphocytic leukemia (CLL), but high-risk CLL patients with TP53 aberrations continue to represent a significant unmet medical need. We profiled treatment patterns, outcomes, and adverse effects in a large, unselected cohort of high-risk CLL patients.

Patients and methods: This study retrospectively analyzed clinical data from 1,720 CLL patients diagnosed between 2012 and 2023 within the Helsinki University Hospital district in Southern Finland. We focused on 543 patients who received first-line (1 L) systemic treatment.

Results: Of the 543 treated patients, 78 (14.4%) had a TP53 aberrations. A clear shift in treatment patterns occurred after 2018, with targeted therapies comprising over one-third of 1 L regimens. For high-risk patients, ibrutinib use at the 1 L stage rose dramatically after 2018, replacing chemoimmunotherapy as the most common treatment. This change coincided with a marked increase in the median time-to-next-treatment (TTNT) for high-risk patients, from 21.2 months (2012-2017) to 26.0 months (2018-2023). Increased TP53 and IGHV mutation testing rates facilitated more personalized treatment approaches over time. Adverse events were less frequent in patients receiving targeted therapies (62.1%) compared to those on non-targeted regimens (73.5%). Despite these improvements, the median overall survival (OS) for high-risk patients remained challenging at 47.1 months after 1 L treatment.

Conclusion: The transition to targeted therapies has improved outcomes for high-risk CLL patients. Nevertheless, outcomes for high-risk CLL patients remain inferior to those reported in clinical trials, underscoring the need for real-world evidence and improved therapies.

COVID-19 is a threat to patients with hematological malignancies (HM) even in the Omicron era, because mortality rates are still high in HM patients, and a significant number of patients develop a protracted disease course called "persistent COVID-19 (pCOVID-19)" which can continue for weeks to months. pCOVID-19 can be life-threatening by itself, but also drastically affects the disease course of the underlying HM by delaying or terminating chemotherapy. Also, patients with pCOVID-19 can be potentially contagious, and timing of ending isolation is a dilemma the hematology ward faces. Furthermore, pCOVID-19 has been reported to lead to acquisition of SARS-CoV-2 multidrug-resistant mutations, which is an alarming issue for both the patient and public health. The optimal management method of pCOVID-19 is currently unknown, and because HM patients are excluded from randomized clinical trials, evidence is limited to case reports and small case series. We carried out a comprehensive literature review of Omicron pCOVID-19 occurring in HM patients, compiled the scattered evidence, and provide practical recommendations which can be of guide to clinicians. Main topics discussed within this review include efficacy of vaccinations in HM patients, risk factors for developing pCOVID-19 (B-cell depleting agents, bendamustine + rituximab therapy, bispecific T-cell engagers, etc.), treatment of pCOVID-19 including extended/sequential/combination therapy incorporating antivirals (nirmatrelvir/ritonavir, remdesivir, molnupiravir, and ensitrelvir) and convalescent plasma/intravenous immunoglobulin therapy, monitoring pCOVID-19 with reverse transcription (RT)-PCR, and optimal target cycle threshold values as goals of therapy.