Clinical Lymphoma, Myeloma & Leukemia最新文献

Background: Early continuous lenalidomide use for multiple myeloma (MM) treatment has led to more patients with lenalidomide-refractory disease at earlier lines of therapy (LOTs). Real-world treatment practices and outcomes in elderly patients with comorbidities are not well characterized.

Materials and methods: Using the Surveillance, Epidemiology, and End Results-Medicare database, we analyzed data from patients who were diagnosed with MM between 2014 and 2019, had 1 to 3 prior LOTs, including a proteasome inhibitor and an immunomodulatory drug, and were lenalidomide refractory. Patients were followed from index (initiation of first subsequent LOT after meeting eligibility criteria and after January 1, 2016) until death, end of continuous Medicare enrollment, or December 31, 2020.

Results: This analysis included 1297 patients (median age, 75 years). The mean National Cancer Institute Comorbidity Index score was 0.87 and 81% had at least 1 comorbidity. Singlet, doublet, and triplet therapies each accounted for ∼30% of index regimens. The most common regimens, ± corticosteroid, were daratumumab-pomalidomide (15%), pomalidomide (13%), and daratumumab (12%). Median overall survival and time to next treatment (TTNT) were 29.3 and 8.5 months, respectively. TTNT decreased with successive LOTs (1 prior LOT, 11.0 months; 3 prior LOTs, 6.1 months).

Conclusion: Elderly patients with comorbidities and lenalidomide-refractory disease after 1 to 3 LOTs receive suboptimal regimens, have poor outcomes, and move rapidly through treatments, highlighting the need for new effective treatments for this difficult-to-treat population.

Therapeutic strategies for chronic myeloid leukemia (CML) are rapidly evolving, with novel agents emerging to address the limitations of current treatments. Goals of CML management are disease control and achieve a deep and sustained molecular response for a possible successful treatment-free remission (TFR). However, a significant proportion of patients fail to reach adequate molecular response and require sequential therapies. A crucial aspect of treatment resistance lies in the persistence of leukemic stem cells (LSCs), which serve as a reservoir for disease recurrence. Increasing focus is placed on combination strategies to overcome the constraints of TKI monotherapy. Various strategies have been explored, starting with the combination of interferon (IFN) and TKIs. The investigation of alternative administration methods, dosing regimens, or extended treatment durations in clinical trials involving IFN represents potential avenues to address current conflicting results. Additionally, the combination of ATP-competitive TKIs with asciminib has shown encouraging preclinical and clinical results, with further data needed for a comprehensive safety profile. Recently, efforts to inhibit other signaling pathways have been explored but with contrasting results. Despite ongoing advancements, TKIs remain the cornerstone of both current and future combination therapies. Their integration with personalized approaches is crucial to overcome complex biological challenges and ensure long-term, effective and safe treatment for CML patients.

Background: Survival in mantle cell lymphoma (MCL) has improved over time, with 1 potential reason being approval of new therapies. We hypothesized that access to multiple new agents with nonoverlapping mechanisms of action would result in significant improvements in overall survival.

Patients and methods: Patients ages > 65 and diagnosed with MCL between 2002 and 2019 were identified using the SEER-Medicare linked database. Lines of therapy were determined using billing codes. Overall survival 1 (OS1) was defined as time of initial therapy to death, while OS2 was defined as time of second-line therapy to death. Time to next therapy (TTNT) was defined as time from first-line therapy to death or start of second-line therapy. Analyses were stratified by both year of diagnosis and year of treatment categories.

Results: In total, 5,441 patients were included; 4,382 patients (79.5%) had claims for first-line regimens and 1,538 (34.1%) for second-line regimens. In the first-line, use of rituximab-bendamustine (BR) increased from < 2% of patients diagnosed between 2002 and 2005 to 54% between 2014 and 2019. BTK-inhibitor (BTKi)-containing regimens, approved in 2013 for use in the second-line, accounted for 8% of first-line and 54% of second-line regimens among those diagnosed between 2014 and 2019. OS1 was significantly improved across year of diagnosis categories (P < .0001), with improvements also seen in TTNT and OS2.

Conclusion: We observed improvements in both OS1 and TTNT over time, which may correlate with increased BR and BTKi use as first-line agents. Unexpectedly, OS2 improvements were more modest. These data support the need for continued development of new therapies in MCL.

Measurement of 24- hour urine protein electrophoresis (PEP) and immunofixation (IFE) are part of standard diagnostic evaluation and monitoring of patients with suspected and diagnosed monoclonal plasma cell disorder for baseline evaluation of renal dysfunction or nephrotic syndrome. Measurement of 24-hour urine protein can however be time consuming and cumbersome and many centers have moved towards random urine protein measurements. The evidence for correlation between spot urine protein creatinine ratio (SUPC) and 24-hour urine protein measurements its scarce. Therefore, we have carried out a prospective study with a sample size of 40 multiple myeloma (MM) patients to demonstrate this correlation. Our results suggest a good correlation between SUPC and 24-hour urine protein measurements, suggesting SUPC testing is a reliable and easier alternative to 24-hour urine collection. These findings should now be confirmed in larger patient populations including early stage plasma cell disorders, light chain amyloidosis and symptomatic MM.

Recent years have brought a much-needed paradigm shift to the management and treatment of mature B-cell lymphomas. Pathophysiologic and clinical heterogeneity within the various subtypes have historically contributed to treatment challenges and differences in outcomes. Novel genomic tools and therapeutic modalities give promise for improved patient outcomes, but are also making treatment planning increasingly complex. To bridge the gaps between therapeutic advancements and clinical practice, an assembly of multidisciplinary hematologic oncology faculty convened to deliberate on the prevailing challenges, knowledge gaps, and controversies in B-cell lymphoma and chronic lymphocytic leukemia management. Many controversies and questions were identified regarding treatment selection, sequencing, and high-risk subtypes. There is a need for head-to-head trials in this therapeutic area to help answer some of these questions. The insights explored and the gaps in knowledge identified by this panel will inform a follow-up conference in 2025 that will employ the modified Delphi method to develop and publish formal consensus recommendations that can provide actionable guidance to practicing clinicians.

Background: Despite treatment improvements a considerable proportion of newly diagnosed multiple myeloma (MM) patients experience early progressive disease (EPD) defined as progression or relapse in < 18 months following initial response to first line treatment.

Methods: We evaluated 1436 newly diagnosed MM patients out of whom 23.3% had EPD.

Results: Patients with EPD had higher median age, β2-microglobulin, LDH and lower hemoglobin and eGFR, compared to others (P < .05); EPD population presented more commonly with advanced stage (ISS3, RISS3, and R2-ISS stage III/IV). Ultra-high-risk MM (UHR-MM) i.e., detection of ≥ 2 high-risk molecular abnormalities was more frequent in EPD population (P < .001). The percentage of patients treated with lenalidomide-based regimens was not significantly different. Daratumumab-based therapies (DBT) were administered less frequently in patients with EPD (2% vs. 10%; P < .001); 11% of patients with EPD versus 33% underwent ASCT (P < .001); Complete response to induction therapy was significantly lower in EPD patients (12% vs. 27%; P < .001). Binary logistic regression analysis demonstrated that ISS, RISS, R2-ISS, UHR-MM, ASCT and DBT were significant predictors for EPD (P < .05). In multivariate analysis R2-ISS, ASCT, and DBT were independent prognosticators for EPD (P < .001). Median PFS and OS were 10 versus 40 months and 29 versus 76 months in patients with EPD versus others, respectively (P < .001).

Conclusion: In real-world, EPD is observed in more than one-fifth of patients, and it remains an unmet clinical need. Daratumumab-based therapies and ASCT significantly reduce the probability of EPD, while R2-ISS could serve as a useful prognostic tool for recognizing this population and guide therapeutic decisions.

The long-term outcome of older patients with acute lymphoblastic leukemia (ALL) is poor due to a reduced ability to tolerate intensive chemotherapy, a more aggressive disease biology, and the presence of comorbidities. Older adults with Philadelphia chromosome-negative (Ph-) B-cell ALL have the highest rates of treatment failure and complications, and the pediatric-inspired regimens that are effective in younger adults are severely limited by their toxicity in older patients. Targeted therapies, including inotuzumab ozogamicin (InO) and blinatumomab, have potent activity in B-cell ALL and are used today as single agents, and in combination with chemotherapy in both salvage and frontline ALL therapy. Optimized frontline use of B-cell targeting agents would potentially reduce the need for, and exposure to, conventional chemotherapy and improve the tolerance and efficacy of reduced-intensity chemotherapy regimens combined with targeted therapies. This review summarizes the efficacy and safety results of several recent trials investigating different approaches with InO as first-line therapy in patients with Ph- B-cell ALL.

Background: Multiple myeloma (MM) is predominantly a disease of the elderly, but approximately 10% of patients are younger than 50 years at diagnosis.   METHODS: This study aimed to investigate the clinical characteristics, treatment outcomes, and prognostic factors in younger MM patients using retrospective data from the Balkan Myeloma Study Group registry.   RESULTS: A total of 350 patients under 50 years old were included, comprising 10.4% of the overall cohort. The study found that younger patients had lower rates of renal impairment and anemia but a higher incidence of lytic bone disease and adverse cytogenetics. Treatment regimens, including proteasome inhibitors and immunomodulatory agents, were comparable between younger and older patients, but younger patients had significantly better complete response rates and overall survival (OS). The 5- and 10-year OS rates were 76% and 64%, respectively, with a projected median OS exceeding 15 years. Factors such as anemia, hypercalcemia, and high-risk cytogenetics were associated with worse survival outcomes. Autologous stem cell transplantation (ASCT) emerged as a key contributor to improved progression-free survival (PFS) and OS.

Conclusion: In conclusion, younger MM patients exhibit distinct disease features and benefit from intensified treatment approaches, underscoring the need for tailored therapies to achieve potential disease cure.

Background: In vivo T-cell depletion with antithymocyte globulin (ATG), especially at high-doses has been shown to be associated with increased incidence of infections after allogeneic hematopoietic stem cell transplantation (HSCT). However, it remains unclear whether ATG, even at low-doses increases the risk of posttransplant infections in the high-risk HSCT setting.

Patients and methods: We conducted a single-center retrospective study of viral and fungal infections early after transplantation, using the data from 82 patients with hematological malignancies. Among them, 42 underwent HLA-mismatched HSCT using low-dose (2.5 mg/kg n = 41, 2.0 mg/kg n = 1) thymoglobulin (ATG patients), and 40 control patients received HSCT without ATG (non-ATG patients) during the same period. Cord blood transplantation patients were excluded. All ATG patients had hematological malignancies not in remission at the time of transplantation, and were considered to be at high-risk for posttransplant infections.

Results: There were no appreciable between-group differences in the incidence of clinically significant cytomegalovirus infection (csCMVi), late-onset CMV reactivation after discontinuation of letermovir, invasive fungal diseases or Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease. Peak values of CMV antigenemia were almost equal in ATG and non-ATG patients. The prevention of csCMVi with letermovir was constant in the 2 groups. However, ATG patients showed earlier reactivation of CMV and higher incidence of EBV viremia than non-ATG patients. Among their underlying diseases, mature T-cell neoplasm was a significant risk factor for CMV/EBV reactivation.

Conclusion: The use of low-dose thymoglobulin in HLA-mismatched HSCT for nonremission hematological malignancies is a reasonable strategy under careful monitoring for viral reactivation.