Clinical Lymphoma, Myeloma & Leukemia最新文献

Introduction: Plasma cell leukemia (PCL) is a rare malignancy with poor overall survival (OS). Recently, its diagnostic criteria were revised by lowering the threshold of circulating plasma cells from ≥ 20% to ≥ 5%.

Methods: Between 2010 and 2024, patients with primary PCL (pPCL) and secondary PCL (sPCL) were identified at a tertiary center. We retrospectively analyzed baseline characteristics, treatment, and survival in months (m).

Results: We identified 30 patients with pPCL and 29 patients with sPCL. The median time to sPCL in patients who received Daratumumab (Dara)-containing regimens for multiple myeloma was 46.8m compared with 12.3m in patients who did not (P=0.007). Of the whole cohort, 51.9% received an induction regimen with novel agents without chemotherapy. Of the evaluable patients with pPCL and sPCL, 82.1% (23/28) and 64.7% (11/17) achieved partial response or better respectively. Median progression free survival was significantly worse in patients with sPCL than pPCL (2.2 vs. 38.3 months; HR 0.16; 95% CI (0.07-0.35), P < .001). Median OS was also worse in patients with sPCL compared with pPCL (3.1 months vs. NR [not reached]; HR 0.09; 95%CI 0.04-0.23, P < .001). The median post-SCT survival for patients with pPCL was NR compared with 6.7m for patients with sPCL (HR 0.17; 95% CI (0.03-0.83), P = .03). Dara-refractory status was associated with worse OS (HR 5.63; 95% CI (2.75-11.51), P < .0001).

Conclusion: Outcomes of pPCL are improving but remain dismal for sPCL. We explored the role of novel agents, especially Dara, in the treatment of PCL. More prospective trials are needed to improve its outcomes.

Background: Detecting anthracyclines-induced cardiotoxicity before the onset of left ventricular dysfunction could enable the timely initiation of cardioprotective measures. 2D-Echocardiography (ECHO) with global longitudinal strain (GLS) and cardiac biomarkers are valuable for the early prediction of cardiotoxicity.

Objectives: We aimed to evaluate the predictive utility of 2D-ECHO-GLS and cardiac biomarkers exclusively in patients with lymphoma treated with a doxorubicin-based regimen.

Methods: The study included lymphoma patients ≥14 years of age of either sex who were planned for a doxorubicin-based regimen. All eligible patients underwent 2D-ECHO-GLS and cardiac biomarkers (troponin T and pro-brain natriuretic peptide) measurements at the baseline (V1), after 3^rd chemotherapy cycle (V2), and after treatment completion (V3). Incidence, risk factors, and early predictors for cardiotoxicity were assessed using SPSS software version 25. The study was registered with CTRI (CTRI/2021/07/034518).

Results: 40 patients (median age, 42 years) had evaluations available at all 3 time points. Three out of 40 (7.5%) patients developed cardiotoxicity at V3. Patients with cardiotoxicity had a significantly higher mean age (P = .045) and a greater incidence of hypertension (P = .012) than those without cardiotoxicity. At V2, the mean GLS threshold (-18.1%) and Δ GLS threshold ≥15% from baseline were significant early predictors of subsequent cardiotoxicity. Despite an exponential rise from V1 to V3, the cardiac biomarkers failed to predict cardiotoxicity.

Conclusions: Patients with lymphoma treated with doxorubicin-based regimens have a significant risk of developing cardiac dysfunction. A greater than 15% fall in GLS from baseline after 3^rd chemotherapy cycle could predict subsequent cardiotoxicity.

Acalabrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKi), offers an improved safety profile compared to first-generation inhibitors like ibrutinib. While BTKi guidelines exist, practical differences between BTKis-such as drug interactions and tolerance-are not fully addressed. Therefore, a consensus on acalabrutinib use would benefit the medical community. This 2-round Delphi study involved hematologists, pharmacists, cardiologists, dermatologists, and nurse practitioners throughout France to establish consensus-based practical guidance on managing adverse events (AEs) associated with acalabrutinib in chronic lymphocytic leukemia. Key findings highlighted the need for a hospital pharmacist to analyze drug interactions before starting acalabrutinib. Additionally, the experts' opinion was to avoid the concomitant use of acalabrutinib with strong CYP3A inhibitors due to an increased risk of toxicity and with strong CYP3A inducers due to potential efficacy concerns. Importantly, our study did not find contraindications for acalabrutinib in patients with current or previous atrial fibrillation. The panel emphasized the importance of measuring blood pressure at every clinical visit for patients treated with acalabrutinib and opposed the initiation of acalabrutinib in patients on both aspirin and clopidogrel. For invasive dermatological or dental procedures, acalabrutinib should be discontinued 4 days prior and resumed 48 hours postprocedure in the absence of bleeding. Additionally, patients should be informed about the risk of headaches, particularly during the first month of treatment, and paracetamol use in combination with caffeine is recommended for managing grade ≥ 2 headaches under acalabrutinib treatment. This Delphi study underscored the effectiveness of a collaborative process in enhancing the management of acalabrutinib-associated AEs.

The availability of effective therapies for multiple myeloma (MM) has sparked debate on the role of first line autologous stem cell transplantation (ASCT), particularly in standard-risk patients. However, treatment for individuals with high-risk disease continues to display suboptimal outcomes. With novel therapies used earlier, practice is changing rapidly in the field of MM. Presently, quadruplet induction therapy incorporating an anti-CD38 monoclonal antibody to a proteasome inhibitor and an immunomodulatory drug prior to ASCT followed by maintenance therapy stands as the foremost strategy for attaining deep and sustained responses in transplant eligible MM (TEMM). This Canadian Consensus Guideline Consortium (CGC) proposes consensus recommendations for the first line treatment of TEMM. To address the needs of physicians and people diagnosed with MM, this document focuses on ASCT eligibility, induction therapy, mobilization and collection, conditioning, consolidation, and maintenance therapy, as well as, high-risk populations, management of adverse events, assessment of treatment response, and monitoring for disease relapse. The CGC will periodically review the recommendations herein and update as necessary.

The survival outcomes of patients with chronic myeloid leukemia (CML) have significantly improved due to the introduction of adenosine triphosphate (ATP) -competitive ABL1 tyrosine kinase inhibitors (TKIs). However, several patients with CML eventually develop treatment resistance or intolerance during the course of ATP-competitive ABL1 TKI treatment. ABL1 TKIs inhibit other tyrosine kinases via their off-target effects. This mechanism leads to the development of adverse events, which may result in treatment discontinuation. Asciminib is a first-in-class STAMP (specifically targeting the ABL myristoyl pocket) inhibitor used in patients with chronic-phase CML who exhibit resistance or intolerance to two prior TKI therapies. Asciminib was found to have excellent efficacy and safety therapeutic profiles. The lack of comprehensive reviews about asciminib, thus, the current study aimed to evaluate the clinical and preclinical evidence of the efficacy and safety of asciminib.

Purpose: Anemia is a cardinal feature of myelofibrosis often managed with red blood cell (RBC) transfusions, which may contribute to negative prognostic, quality-of-life, and healthcare-related economic impacts. The Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib was approved for the treatment of patients with myelofibrosis and anemia based on clinical trial evidence of anemia, spleen, and symptom benefits illustrated using binomial response/nonresponse endpoints. In the present post hoc, descriptive analyses, the impact of momelotinib on RBC transfusion burden over time was further characterized across JAK inhibitor-naive and -experienced patients.

Methods: All RBC units transfused were collected during the baseline and 24-week treatment periods, initially in a single-arm phase 2 study as proof-of-concept analysis, and then versus comparators (ruxolitinib, best available therapy [BAT], and danazol) in the phase 3 SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM studies, respectively.

Results: In the phase 2 study, mean transfusion requirement changed by -1.5 units/28 days, with 85% of patients (35/41) achieving numeric transfusion reduction. Across SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM, mean transfusion requirements decreased with momelotinib (-0.1, -0.36, and -0.86 units/28 days), while mean requirements with ruxolitinib, BAT, and danazol changed by +0.39, 0, and ‒0.28 units/28 days, respectively. Overall, 87% (185/213), 77% (79/103), and 85% (110/130) of patients had improved or stable transfusion intensities with momelotinib versus 54% (117/216), 62% (32/52), and 63% (41/65) with ruxolitinib, BAT, and danazol.

Conclusion: These novel time-dependent transfusion burden analyses demonstrate that momelotinib is associated with anemia-related benefits in most patients and greater transfusion burden reduction versus comparators.

Trial registration: ClinicalTrials.gov identifiers: NCT02515630, NCT01969838, NCT02101268, NCT04173494.

MCL remains incurable, and patients who relapse post BTK inhibitors have poor outcomes. BsAbs and CAR T cell therapy are novel strategies to treat patients with R/R MCL. These therapies exhibit favorable outcomes and side effect profiles in a previously dismal space. This review looks to detail the current data available for BsAbs and CAR T cell therapy in R/R MCL, and how are current treatment paradigm is shifting to incorporate these novel agents.

Background: Monoclonal insulin autoimmune syndrome (IAS) is a very rare disease characterized by severe attacks of hypoglycemia caused by circulating anti-insulin antibodies produced by a B-cell clone, usually clonal plasma cells.

Method: We present 2 female Norwegian patients with monoclonal IAS. The anti-insulin antibodies were quantified by immune precipitation and characterized using a 3-step manual in-house assay. Both patients received plasma cell directed therapy.

Result: The first patient received plasma cell directed therapy for a time-limited period and achieved a sustained clinical remission without detectable anti-insulin antibodies. The second patient receives continuous plasma cell directed therapy and is in clinical remission with low values of detectable anti-insulin antibodies.

Conclusion: Plasma cell directed therapy was effective and safe in our 2 cases of monoclonal IAS. We recommend considering plasma cell directed therapy for these patients.

Background: Recent approvals of chimeric antigen receptor T-cells (CAR T) and bispecific antibody therapies offer new hope for relapsed refractory multiple myeloma (RRMM) patients, with superior efficacy over standard regimens observed in clinical trials. However, relapse after BCMA-directed therapy is common and requires further investigation.

Patients and methods: We conducted a retrospective cohort study on 57 RRMM patients treated with BCMA-directed CAR T. Only the patients who had an initial response and lost BCMA-expressing identified PC following CAR T infusion at Day 30 were included in the analysis. Multicolor flow cytometry (MFC) to detect BCMA + plasma cell (PC) re-emergence was performed on bone marrow samples at defined intervals and clinical responses were assessed using International Myeloma Working Group criteria.

Results: The majority of patients achieved undetectable BCMA on MFC postinfusion, with subsequent BCMA+ PC re-emergence observed in 55% of cases. Notably, 91% of patients experiencing clinical relapse showed BCMA+ PC re-emergence, often preceding relapse. Early relapse (<6 months) was associated with earlier BCMA re-emergence.

Conclusion: Early BCMA+ PC re-emergence may serve as a prognostic marker for clinical relapse post-BCMA CAR T therapy. Monitoring BCMA+ PC levels via MFC offers potential for early relapse detection and informed treatment decisions. Further studies, including novel BCMA-directed minimal residual disease (MRD) detection technologies, are warranted to validate these findings and refine RRMM management strategies.

Background: This noninterventional postauthorization safety study assessed the safety and effectiveness of lenalidomide in patients with transfusion-dependent, International Prognostic Scoring System (IPSS) Low- or Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) associated with isolated deletion of 5q (del[5q]) who were treated in routine care.

Patients and methods: Eligible adult patients in the lenalidomide cohort had transfusion-dependent, IPSS Low- or Int-1-risk MDS and isolated del(5q) and had received ≥ 1 dose of lenalidomide between 2014 and 2022. The primary endpoint was the 24-month cumulative incidence of acute myeloid leukemia (AML) progression. Overall survival (OS) was estimated by Kaplan-Meier analysis and safety data were collected.

Results: In total, 296 patients received ≥ 1 dose of lenalidomide (lenalidomide cohort, safety population) and 277 had received ≥ 1 complete cycle of lenalidomide (primary population). In the safety population, 44.3% of patients completed 3-year follow-up and 55.1% discontinued, with 33.1% discontinuing due to death. In the primary population, 24-month cumulative incidence of AML progression was 12.7% (95% confidence interval, 8.9%-17.1%) and estimated OS probability was 78.3% at 24 months and 63.9% at 36 months. Grade 3/4 treatment-emergent adverse events were experienced by 67.2% of the safety population, and these led to discontinuation in 35.5% of patients. There were no new safety signals.

Conclusion: These real-world data support the established benefit-risk profile of lenalidomide in transfusion-dependent IPSS Low- or Int-1-risk MDS with isolated del(5q).