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.

