Clinical Lymphoma, Myeloma & Leukemia最新文献

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.

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: 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).

Introduction: Obinutuzumab is hypothesized to improve progression-free survival (PFS) combined with bendamustine induction in mantle cell lymphoma (MCL). Measurable-residual disease (MRD) testing may predict benefit from maintenance therapy.

Methods: Adults (≥ 18 years) with untreated MCL ineligible for intensive therapies received 4 to 6 cycles of bendamustine + obinutuzumab (BO) followed by consolidation obinutuzumab (CO). Restaging after CO included MRD assessment by next-generation sequencing of bone marrow aspirate (BMA) and peripheral blood (PB). Maintenance obinutuzumab (MO) was omitted for patients with imaging complete response (CR) and MRD-negativity in PB/BMA. All other patients received 8 cycles MO. Primary endpoint is PFS; secondary endpoints are response rates, overall survival, and estimation of MRD status.

Results: Twenty-one patients enrolled, with median age 70 years and stage IV disease in 95%. Twenty patients completed BO; 10 patients received MO per protocol. Six patients did not complete MO due to progression (n = 4), infection (n = 1) and carcinoma (n = 1). Overall response is 95% (75% CR, 20% partial response). Concordance rate between post-consolidation MRD testing in PB and BMA was 70%. After a median follow-up of 43.9 months, median PFS is 46.5 months. The observed difference between 2-year PFS in groups receiving MO versus observation was not statistically significant (HR 0.45, 95% CI, 0.10-1.91). Most common grade 3/4 toxicities were neutropenia, leukopenia, and infections.

Conclusions: BO is a tolerable induction regimen with higher rates of CR compared with historical rates with bendamustine + rituximab. Omission of MO did not worsen outcomes in patients achieving MRD-negative status after nonintensive induction/consolidation therapy.

Introduction: We performed a retrospective analysis of patients with multiple myeloma (MM) receiving palliative radiotherapy (RT) and assessed factors associated with local control, with a focus on dose/fractionation and cytogenetics.

Materials and methods: We included patients who received palliative RT for MM at our institution. Cytogenetics were collected via fluorescence in situ hybridization. Follow-up imaging was used to assess local control.

Results: A total of 239 patients with 362 treated lesions were included. Eighty-six (36.0%) patients had high-risk cytogenetics. Most lesions received 20 Gray (Gy) in 5 fractions (131, 36.2%), 8 Gy in 1 fraction (93, 25.7%), or 30 Gy in 10 fractions (48, 13.3%). At a median follow-up of 4.3 years, 4-year local progression was 13.4% (95% confidence interval [CI]: 10.3-17.5). No cytogenetic abnormalities were correlated with local progression, nor were double- and triple-hit status. There was a nonsignificant trend toward association between number of treated lesions and local progression (HR for >3 vs. 1: 2.43 [95% CI: 0.88-6.74], P = .059). Among patients with >3 treated lesions, equivalent dose in 2 Gy fractions ≥20 Gy reduced progression (HR: 0.05 [95% CI: 0.01-0.23], P = .0001).

Conclusion: In this large study of patients with MM, modern palliative RT achieved excellent rates of long-term local control. Although there was no dose-response observed in the overall cohort, patients with high volume symptomatic disease may benefit from EQD2 ≥20 Gy. High-risk cytogenetics did not appear to influence radioresponsiveness, and standard radiation doses appear to be effective for all MM patients regardless of cytogenetics.

Background: Prognostic models in peripheral T cell lymphoma (PTCL) have identified biological factors including age, performance status, LDH, and BM involvement as prognostic for survival. The association of social determinants of health (SDH), on PTCL outcomes remains unexplored.

Methods: To evaluate the impact of actionable SDH on PTCL mortality across race groups, we conducted a retrospective cohort study that included all White, Hispanic, Asian/Pacific Islander (PI) and Black adult patients with nodal PTCLs , diagnosed 2000-2020, in California. We utilized Chi² and Wilcoxon rank-sum tests for descriptive metrics and Kaplan-Meier statistics for mortality estimation. Regression models included patient- (age, sex, race, stage, Charlson Comorbidity Index, histology, treatment, academic center treatment, payer), and neighborhood-level factors (socioeconomic (SES) quintile, proportion without a high school diploma, and rural/urban). Risk factors significant in univariate regression of P < .10 were incorporated into the multivariable model.

Findings: Our analysis included 6158 patients: 51.8% White, 25.8% Hispanic, 14.7% Asians/PI, and 7.6% Black. Hispanics exhibited the longest median survival (33 months) followed by Whites, Blacks, and Asian/PI (25, 20, and 14 months, respectively; P = .011). Risk factors independently associated with inferior lymphoma-specific survival (LSS) included Asian/PI compared with NH Whites (HR, 1.23; 95% CI, 1.10-1.34; P = .0002), AITL/ALCL compared with PTCL, NOS (AITL HR, 1.14; 95% CI, 1.02-1.25; P = .011; ALCL HR, 1.15; 95% CI, 1.04-1.26; P = .004), academic compared to nonacademic facility-type (HR 0.71; 95% CI, 0.64-0.77; P < .01), Medicare compared with uninsured (HR 1.48, 95% CI, 1.25-1.73; P < .01), and the lowest 3 compared to the highest education quartiles (Q2 HR 1.13; 95% CI, 1.01-1.25; P = .021; Q3 HR 1.14; 95% CI, 1.02-1.26; P = .018; Q4 HR 1.22; 95% CI, 1.08-1.36; P < .001). In the least resourced patients, histology, treatment, treatment facility-type, payer and education were independently prognostic for LSS. Academic center treatment was associated with a striking improvement in LSS (academic institution: yes = 101 months, no = 17 months; P < .01).

Interpretation: Treatment facility-type, payer and education, areindependent actionable SDH for PTCL mortality. Treatment center-type had the strongest prognostic association with LSS, conferring a risk reduction of PTCL mortality by nearly 30%.

Introduction: Multiple myeloma patients aged 80 years and older are a population more prone to comorbidities and frailty. We aim to describe the real-life management and outcomes of this population. EMMY is a descriptive large-scale study.

Patients: Between 2017 and 2021 we included 4383 patients of which 894 (20.3%) were aged ≥ 80 years. Four cohorts of patients aged ≥ 80 years were analysed: line 1 (L1), line 2 (L2), line 3 (L3) or line 4+ (L4+).

Results: The proportion of patients ≥ 80 years old was 20.8% in L1, 21.3% in L2, 20.9% in L3 and 17.8% in L4+. L1 patients received more treatment including a proteasome inhibitor (PI) (42.9%), L2 patients received mainly an immunomodulator (IMID) (65.9%) or an anti-CD38 (31.5%). For L3, IMID was used in 71.4% than an anti-CD38 (33.5%). L4+ patients received a PI (40.6%), IMID (33.2%) or an anti-CD38 (29.1%). Regarding efficacy, the median progression-free survival was 18.4 months in L1, 15.1 months in L2, 10.4 months in L3 and 6.5 months in L4+. The median overall survival was 49 months in L1, 31.3 months in L2, 21.4 months in L3 and 13.6 months in L4+.

Conclusion: EMMY cohort confirmed that patients ≥ 80 years of age represent an important proportion of MM patients, in the de novo or relapse setting. This study is an important step in improving our comprehension and management of treatment in elderly patients.