Search

The registered dose for imatinib is 400 mg/d, despite high inter-patient variability in imatinib plasmatic exposure. Therapeutic drug monitoring (TDM) is routinely used to maximize a drug's efficacy or tolerance. We decided to conduct a prospective randomized trial (OPTIM-imatinib trial) to assess the value of TDM in patients with chronic phase chronic myelogenous treated with imatinib as first-line therapy (NCT02896842). Eligible patients started imatinib at 400 mg daily, followed by imatinib [C]min assessment. Patients considered underdosed ([C]min < 1000 ng/mL) were randomized in a dose-increase strategy aiming to reach the threshold of 1000 ng/mL (TDM arm) versus standard imatinib management (control arm). Patients with [C]min levels ≥ 1000 ng/mL were treated following current European Leukemia Net recommendations (observational arm). The primary endpoint was the rate of major molecular response (MMR, BCR::ABL1IS ≤ 0.1%) at 12 months. Out of 133 evaluable patients on imatinib 400 mg daily, 86 patients had a [C]min < 1000 ng/mL and were randomized. The TDM strategy resulted in a significant increase in [C]min values with a mean imatinib daily dose of 603 mg daily. Patients included in the TDM arm had a 12-month MMR rate of 67% (95% CI, 51–81) compared to 39% (95% CI, 24–55) for the control arm (p = 0.017). This early advantage persisted over the 3-year study period, in which we considered imatinib cessation as a censoring event. Imatinib TDM was feasible and significantly improved the 12-month MMR rate. This early advantage may be beneficial for patients without easy access to second-line TKIs. [ABSTRACT FROM AUTHOR]

The study included patients with HL relapsing or refractory after three lines of chemotherapy (including brentuximab-vedotin) and autoHSCT, or four lines of chemotherapy if the patient was not eligible for HSCT. To assess whether some patients might be cured with nivolumab alone as systemic treatment, we analysed the 19 patients who achieved a CR and did not receive a consolidation (concomitant radiotherapy was performed in five patients). Can nivolumab alone cure patients with relapse or refractory Hodgkin lymphoma?. [Extracted from the article]

Objective: Many salvage therapies have been proposed for relapsed/refractory (R/R) diffuse large B-cell lymphomas or for consolidation in the case of suboptimal response. Radiotherapy (RT) is one modality of salvage therapy, but its place is currently not well defined. Method: This study reports a retrospective review of patients receiving unplanned radiotherapy for R/R diffuse large B-cell lymphoma (DLBCL) or primary mediastinal B-cell lymphoma (PMBCL), or as consolidation therapy after second-line chemotherapy, treated in our hospital. Results: Fifty-one patients with a median age of 53.5 years [19-89] were selected. The histologic type was DLBCL in 35 cases (68%), PMBCL in 8 cases (16%), and secondary transformed NHL in 8 cases (16%). Median aaIPI was 1 [0-4], and 17 patients (33%) had a high tumor burden (bulky disease). Sixteen patients (31%) were irradiated for a response considered to be insufficient, 18 patients (36%) were refractory, and 17 patients (33%) had relapsed. Patients were irradiated with a median dose of 40 Gy [15-44], 29 (57%) by a conformal 3D technique and 22 (43%) by tomotherapy. With a median follow-up of 36 months [1.0-127.8] after irradiation, 5-year progression-free survival (PFS) and overall survival (OS) were 62% and 72%, respectively. In multivariate analysis, adverse factors associated with PFS and OS in our cohort were age >70 years (HR = 5.06, P = .02) and post-RT relapse (HR = 12.24, P = .002), whereas favorable factors were number of lines of chemotherapy <3 (HR = 0.02, P = .03) and bulky disease (HR = 0.02, P = .009). Conclusion: Due to its low toxicity and ease of use, radiotherapy should therefore remain an available option in patients with R/R DLBCL or as consolidation therapy in patients with high-risk disease, mostly in patients with chemo-sensitive disease or bulky disease. [ABSTRACT FROM AUTHOR]

Although purine analogues have significantly improved the outcome of hairy cell leukaemia ( HCL) patients, 30-40% relapse, illustrating the need for minimal residual disease ( MRD) markers that can aid personalized therapeutic management. Diagnostic samples from 34 HCL patients were used to design an 8-colour flow cytometry (8- FC) tube for blood MRD (B/ RD) analysis (188 samples) which was compared to quantitative IGH polymerase chain reaction (Q- PCR) on 83 samples and to qualitative consensus IGH PCR clonality analysis on 165 samples. Despite heterogeneous HCL phenotypes at diagnosis, discrimination from normal B lymphocytes was possible in all cases using a single 8- FC tube, with a robust sensitivity of detection of 10−4, comparable to Q- PCR at this level, but preferable in terms of informativeness, simplicity and cost. B/ RD assessment of 15 patients achieving haematological complete remission after purine analogues was predictive of a clinically significant relapse risk: with a median follow-up of 95 months; only one of the nine patients with reproducible 8- FC B/ RD levels below 10−4 (B/ RDneg) relapsed, compared to 5/6 in the B/ RDpos group ( P = 0·003). These data demonstrate the clinical interest of a robust 8- FC HCL B/ RD strategy that could become a surrogate biomarker for therapeutic stratification and new drug assessment, which should be evaluated prospectively. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) might be associated with worse outcome in classical Hodgkin lymphoma (cHL). Our aim was to determine whether TAMs correlated with refractoriness in cHL. In a cohort of 18 consecutive primary refractory or early relapsed cases and 41 randomly selected controls (responder patients), high TAM infiltration was significantly associated with refractoriness or early relapse ( p = 0.004) and remained independently correlated with outcome in multivariate analysis (odds ratio 8.276, 95% confidence interval 1.214-56.408). This study provides evidence that the marker CD68 might accurately predict early outcome of de novo cHL and could be used in combination with c-kit and TiA1 staining. [ABSTRACT FROM AUTHOR]

Long-term efficacy of anti-PD1 therapy and the need for a consolidation with allogenic haematopoietic stem cell transplantation (allo-HSCT) remain unclear in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). We retrospectively analysed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcomes according to subsequent allo-HSCT. After a median follow-up of 34.3 months, the best overall response rate was 65.8%, including 38.2% complete responses (CRs). The median progression-free survival (PFS) was 12.1 months. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a partial response (PR) (median = not reached vs 9.3 months, p < 0.001). In our cohort, 13 patients who responded (i.e. in CR or PR) to nivolumab monotherapy underwent consolidation with allo-HSCT. Among responding patients, none of those who underwent subsequent allo-HSCT (N = 13) relapsed, whereas 62.2% of those who were not consolidated with allo-HSCT (N = 37) relapsed (p < 0.001). There was no difference in overall survival (OS) between the two groups. Five of 6 patients who were not in CR at the time of transplantation (4 PRs and 1 progressive disease) converted into a CR after allo-HSCT. Most patients with R/R HL treated with anti-PD1 monotherapy eventually progressed, notably those who did not achieve a CR. Patients undergoing consolidation with allo-HSCT after anti-PD1 therapy experienced prolonged disease-free survival compared with non-transplanted patients, but this difference did not translate into a benefit in OS. This information should be considered when evaluating the risk/benefit ratio of allo-HSCT after anti-PD1 therapy. • Most patients with relapsed/refractory Hodgkin lymphoma eventually progressed during anti-programmed cell death-1 (anti-PD1) therapy. • In responding patients, the relapse rate was lower in patients consolidated with allogenic haematopoietic stem cell transplantation (allo-HSCT). • Among responders, subsequent allo-HSCT was not associated with a greater overall survival. [ABSTRACT FROM AUTHOR]