Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial

Efficacy of lenalidomide was investigated in 103 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) treated on the prospective, multicenter randomized phase-II CLL-009 trial. Interphase cytogenetic and mutational analyses identified TP53 mutations, unmutated IGHV, or del(17p) in 36/96 (37.5%), 68/88 (77.3%) or 22/92 (23.9%) patients. The overall response rate (ORR) was 40.4% (42/104). ORRs were similar irrespective of TP53 mutation (36.1% (13/36) vs 43.3% (26/60) for patients with vs without mutation) or IGHV mutation status (45.0% (9/20) vs 39.1% (27/68)); however, patients with del(17p) had lower ORRs than those without del(17p) (21.7% (5/22) vs 47.1% (33/70); P=0.049). No significant differences in progression-free survival and overall survival (OS) were observed when comparing subgroups defined by the presence or absence of high-risk genetic characteristics. In multivariate analyses, only multiple prior therapies (greater than or equal to3 lines) significantly impacted outcomes (median OS: 21.2 months vs not reached; P=0.019). This analysis indicates that lenalidomide is active in patients with relapsed/refractory CLL with unfavorable genetic profiles, including TP53 inactivation or unmutated IGHV. (ClinicalTrials.gov identifier: NCT00963105)

Therapeutic strategies and treatment sequencing in patients with chronic lymphocytic leukemia: an international study of ERIC, the European Research Initiative on CLL

FUNDING: This project was supported in part by AbbVie; AIRC under 5 per Mille 2018-ID. 21198 program (to PG and GG); PNRR-MAD-2022-12375673 (Next Generation EU, M6/C2_CALL 2022), Italian Ministry of Health, Rome, Italy, Conceptual development of research organization (FNBr 65269705) provided by the Ministry of Health of the Czech Republic, and National Institute for Cancer Research (Programme EXCELLES, ID Project No. LX22NPO5102) funded by the European Union—Next Generation EU

Acalabrutinib monotherapy in patients with Waldenström macroglobulinemia: a single-arm, multicentre, phase 2 study

Background: Chemoimmunotherapy is typically the standard of care for patients with Waldenström macroglobulinemia; however, infectious and hematologic toxic effects are problematic. Acalabrutinib is a selective, potent Bruton tyrosine-kinase inhibitor. The aim of this trial was to evaluate the activity and safety of acalabrutinib in patients with Waldenström macroglobulinemia. Methods: This single-arm, multicentre, phase 2 trial was done in 19 European academic centres in France, Italy, Greece, the Netherlands, and the UK, and eight academic centres in the USA. Eligible patients were 18 years or older and had treatment naive (declined or not eligible for chemoimmunotherapy) or relapsed or refractory (at least one previous therapy) Waldenström macroglobulinemia that required treatment, an Eastern Cooperative Oncology Group performance status of 2 or less, and received no previous Bruton tyrosine-kinase inhibitor therapy. Patients received 100 mg oral acalabrutinib twice per day in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response (at least a minor response) according to the 6th International Workshop for Waldenström Macroglobulinemia (IWWM) and the modified 3rd IWWM workshop criteria. The primary outcome and safety were assessed in all patients who received at least one dose of treatment. This study is registered with ClinicalTrials.gov, number NCT02180724, and is ongoing, but no longer enrolling. Findings: Between Sept 8, 2014, and Dec 24, 2015, 122 patients were assessed for eligibility, of which 106 (87%) patients were given acalabrutinib (14 were treatment naive and 92 had relapsed or refractory disease). With a median follow-up of 27·4 months (IQR 26·0–29·7), 13 (93% [95% CI 66–100]) of 14 treatment naive patients achieved an overall response and 86 (93% [86–98]) of 92 relapsed or refractory patients per both the modified 3rd and 6th IWWM criteria. Seven (50%) of 14 treatment naive patients and 23 (25%) of 92 relapsed or refractory patients discontinued treatment on study. Grade 3–4 adverse events occurring in more than 5% of patients were neutropenia (17 [16%] of 106 patients) and pneumonia (7 [7%]). Grade 3–4 atrial fibrillation occurred in one (1%) patient and grade 3–4 bleeding occurred in three (3%) patients. The most common serious adverse events were lower respiratory tract infection (n=7 [7%]), pneumonia (n=7 [7%]), pyrexia (n=4 [4%]), cellulitis (n=3 [3%]), fall (n=3 [3%]), and sepsis (n=3 [3%]). Pneumonia (n=5 [5%]) and lower respiratory tract infection (n=4 [4%]) were considered treatment related. One treatment-related death was reported (intracranial hematoma). Interpretation: This study provides evidence that acalabrutinib is active as single-agent therapy with a manageable safety profile in patients with treatment-naive, or relapse or refractory Waldenström macroglobulinemia. Further studies are needed to establish its efficacy against current standard treatments and to investigate whether outcomes can be improved with combination therapies. Funding: Acerta Pharma

Psychological Outcomes and Quality of Life in Relation to Pancreatectomy

International audienceThis review aimed to inventory and analyze previous studies regarding quality of life (QoL) and psychological outcomes in relation to pancreatectomy. PubMed and PsycInfo databases were reviewed using the Preferred Reporting Items for Systematic review and Meta-Analysis guidelines. Thirteen studies were selected, 9 of which focused on the QoL after surgery. Quality of life significantly improved 3 to 6 months after surgery. Regarding the postoperative experience, one study reported high fear of recurrence of cancer, whereas another emphasized various expressions of patient needs. One study explained how strategy and ability to adapt are not related to the type, the cause, nor the physical condition, but are mainly influenced by the age and the subjective experience of the patients. A last study showed that depression did not affect survival rate after surgery. Our systematic review found only few studies regarding the psychological condition after pancreatectomy and highlights the need to describe and characterize the patients' psychological characteristics in this setting

Blood dendritic cells in patients with chronic lymphocytic leukaemia.

International audienceMyeloid and plasmacytoid dendritic cells (MDC, PDC) play a key role in the initiation of immune responses. We found a reduction of both DC subsets in 42 patients with chronic lymphocytic leukaemia (CLL) at diagnosis (P<0.0001 and 0.0001 vs. controls, respectively), likely related to the high secretion of CCL22 and CXCL12 (P=0.04 and 0.008 vs. controls, respectively) by leukaemic cells. However, CD14+ monocytes from CLL patients could give rise to functional IL-12p70-secreting monocyte-derived DCs, capable of inducing a type 1 polarization immunostimulatory profile. These monocyte-derived DCs from CLL patients efficiently migrate in response to CCL19/MIP-3beta chemokine, suggesting that functional autologous DCs can be generated for immunotherapeutic purposes to circumvent DC defects in CLL

Prolymphocytic Leukemia New Insights in Diagnosis and in Treatment

We aimed to produce a comprehensive update on clinical and biological data regarding two rare lymphoid neoplasms, B and T prolymphocytic leukemias, and assess therapeutic management in the light of new molecular insights and the advent of targeted therapies

Post-remission intervention with alemtuzumab or rituximab to eradicate minimal residual disease in chronic lymphocytic leukemia: where do we stand?

The introduction of purine nucleoside analogs, later in combination with alkylating moieties and anti-CD20 immunotherapy, has profoundly improved the response rate and response duration in patients with chronic lymphocytic leukemia (CLL). The quality of clinical response following treatment may be improved to a level where residual leukemic cells become undetectable. As patients with this type of response appear to have extended survival rates, minimal residual disease (MRD) eradication is considered a new objective in CLL treatment with the aim of improving progression-free survival (PFS) and potentially overall survival (OS). This review therefore aims to overview the prognostic value of MRD eradication in CLL, the role of post-remission intervention with "passive" immunotherapy (alemtuzumab or rituximab) so as to eliminate persistent MRD or prevent MRD relapse, the impact of these strategies on disease-free survival and their possible adverse consequences. The data indicate a potential for post-remission alemtuzumab or rituximab to prolong PFS in CLL, although more investigations and longer follow-up are required before MRD-guided strategies can be recommended outside of clinical trials