Ibrutinib followed by ofatumumab consolidation in previously untreated patients with chronic lymphocytic leukemia (CLL): GELLC-7 trial from the Spanish group of CLL (GELLC).

Background: BTK inhibitors have been concurrently administered with anti-CD20 monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL). However, the optimal regimen for combining these two drugs remains pending.

Methods: This multi-center phase 2 study aimed to analyze whether consolidation with ofatumumab improved the response in patients with CLL receiving front-line treatment with ibrutinib.

Management and outcome of patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era - analysis of the European LeukemiaNet Blast Phase Registry.

Blast phase (BP) of chronic myeloid leukemia (CML) still represents an unmet clinical need with a dismal prognosis. Due to the rarity of the condition and the heterogeneity of the biology and clinical presentation, prospective trials and concise treatment recommendations are lacking. Here we present the analysis of the European LeukemiaNet Blast Phase Registry, an international collection of the clinical presentation, treatment and outcome of blast phases which had been diagnosed in CML patients after 2015.

Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.

Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with minimal residual disease (MRD). Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA /GEM2014MAIN trial.

Lenalidomide and dexamethasone maintenance with or without ixazomib, tailored by residual disease status in myeloma.

From November 2014 to May 2017, 332 patients homogeneously treated with bortezomib, lenalidomide, and dexamethasone (VRD) induction, autologous stem cell transplant, and VRD consolidation were randomly assigned to receive maintenance therapy with lenalidomide and dexamethasone (RD; 161 patients) vs RD plus ixazomib (IRD; 171 patients). RD consisted of lenalidomide 15 mg/d from days 1 to 21 plus dexamethasone 20 mg/d on days 1 to 4 and 9 to 12 at 4-week intervals, whereas in the IRD arm, oral ixazomib at a dose of 4 mg on days 1, 8, and 15 was added. Therapy for patients with negative measurable residual disease (MRD) after 24 cycles was discontinued, whereas those who tested positive for MRD remained on maintenance with RD for 36 more cycles.

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors.

(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs.

Real-life disease monitoring in follicular lymphoma patients using liquid biopsy ultra-deep sequencing and PET/CT.

In the present study, we screened 84 Follicular Lymphoma patients for somatic mutations suitable as liquid biopsy MRD biomarkers using a targeted next-generation sequencing (NGS) panel. We found trackable mutations in 95% of the lymph node samples and 80% of the liquid biopsy baseline samples. Then, we used an ultra-deep sequencing approach with 2 · 10 sensitivity (LiqBio-MRD) to track those mutations on 151 follow-up liquid biopsy samples from 54 treated patients.

Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma.

Introduction: Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]).

Materials And Methods: We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial.

Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality.

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals.

Early Prediction of Subsequent Molecular Response to Nilotinib in Patients with Chronic Myeloid Leukemia: Comparison of the Quantification of BCR-ABL1 Ratios Using ABL1 or GUSB Control Genes.

Molecular monitoring of BCR-ABL1 transcripts is a critical prognostic indicator of treatment response in chronic myeloid leukemia (CML). Quantification of BCR-ABL1 transcripts using ABL1 or GUSB as control genes on the early molecular response (MR) to frontline nilotinib was studied using data from 60 patients with chronic-phase CML from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) substudy. Effects of BCR-ABL1/ABL1 and BCR-ABL1/GUSB ratios at early time points as independent variables on subsequent MR were determined by logistic regression analyses and predictive cut-off values determined by receiver operating curve analyses.

Immediate Effects of Dasatinib on the Migration and Redistribution of Naïve and Memory Lymphocytes Associated With Lymphocytosis in Chronic Myeloid Leukemia Patients.

Dasatinib is a dual SRC/ABL tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) that is known to have unique immunomodulatory effects. In particular, dasatinib intake typically causes lymphocytosis, which has been linked to better clinical response. Since the underlying mechanisms are unknown and SRC family kinases are involved in many cell motility processes, we hypothesized that the movement and migration of lymphocytes is modulated by dasatinib.

Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma.

Achieving and maintaining a high-quality response is the treatment goal for patients with newly diagnosed multiple myeloma (NDMM). The phase 3 PETHEMA/GEM2012 study, in 458 patients aged ≤65 years with NDMM, is evaluating bortezomib (subcutaneous) + lenalidomide + dexamethasone (VRD) for 6 cycles followed by autologous stem cell transplant (ASCT) conditioned with IV busulfan + melphalan vs melphalan and posttransplant consolidation with 2 cycles of VRD. We present grouped response analysis of induction, transplant, and consolidation.

Feasibility of treatment discontinuation in chronic myeloid leukemia in clinical practice: results from a nationwide series of 236 patients.

Over half of chronic myeloid leukemia (CML) patients in deep molecular response do not lose the major molecular response (MMR) after stopping treatment with tyrosine kinase inhibitors (TKI). This strategy is safe in clinical trials, but its applicability in the real-life setting remains unsettled. We describe the outcomes after TKI discontinuation in a nationwide series of 236 CML patients.

Cost-utility analysis of idelalisib in combination with rituximab in relapsed or refractory chronic lymphocytic leukaemia.

Objective: To evaluate the incremental cost-utility ratio (ICUR) of idelalisib in combination with rituximab (IR) versus rituximab monotherapy (R) in the treatment of patients with relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL), from the Spanish National Health System (NHS) perspective.

Methods: A partitioned survival Markov model for a lifetime horizon (30 years) was developed to estimate costs (€, 2016) and quality-adjusted life years (QALY) with IR and R. Initial cohort included patients with CLL receiving a second or subsequent line (2L) of treatment with IR or R.

PTCH1 is a reliable marker for predicting imatinib response in chronic myeloid leukemia patients in chronic phase.

Patched homolog 1 gene (PTCH1) expression and the ratio of PTCH1 to Smoothened (SMO) expression have been proposed as prognostic markers of the response of chronic myeloid leukemia (CML) patients to imatinib. We compared these measurements in a realistic cohort of 101 patients with CML in chronic phase (CP) using a simplified qPCR method, and confirmed the prognostic power of each in a competing risk analysis. Gene expression levels were measured in peripheral blood samples at diagnosis.

Economic evaluation of obinutuzumab in combination with chlorambucil in first-line treatment of patients with chronic lymphocytic leukemia in Spain.

Objective: To evaluate the cost-effectiveness of obinutuzumab in combination with chlorambucil (GClb) versus rituximab plus chlorambucil (RClb) in the treatment of adults with previously untreated chronic lymphocytic leukemia (CLL) and with comorbidities that make them unsuitable for full-dose fludarabine-based therapy, from the perspective of the Spanish National Health System.

Methods: A Markov model was developed with three mutually exclusive health states: progression-free survival (with or without treatment), progression, and death. Survival time for the two treatments was modeled based on the results of CLL11 clinical trial and external sources.

Switching to second-generation tyrosine kinase inhibitor improves the response and outcome of frontline imatinib-treated patients with chronic myeloid leukemia with more than 10% of BCR-ABL/ABL ratio at 3 months.

Chronic myeloid leukemia patients display heterogeneous responses to imatinib. Survival depends on baseline clinical characteristics (including prognostic scoring systems) and on early response (such as >10% BCR-ABL/ABL ratio at 3 months of therapy). The results of switching to second-generation tyrosine kinase inhibitors (2GTKIs) may contain a bias since, in the majority of these studies, patients who switch treatment due to intolerance or failure are censored or excluded.

[Economic evaluation of rituximab added to fludarabine plus cyclophosphamide versus fludarabine plus cyclophosphamide for the treatment of chronic lymphocytic leukemia].

Objectives: We evaluated the cost-effectiveness of rituximab added to the chemotherapy regimen of fludarabine plus cyclophosphamide (R-FC) versus fludarabine plus cyclophosphamide (FC) for the treatment of patients with previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL).

Methods: Two Markov models were built, using published results on progression-free survival (PFS) in patients receiving first- or second-line therapy with R-FC vs FC, rates of disease progression and mortality rates in Spain. Patient-elicited utilities were applied to PFS and progressed health states.

Incidence of cytomegalovirus infection and disease in patients with lymphoproliferative disorders treated with alemtuzumab.

The aim of this study was to assess the incidence of cytomegalovirus (CMV) infection and disease in patients with hematologic malignancies treated with alemtuzumab. The outcome of CMV infection in hematologic patients treated with alemtuzumab in 19 hospitals throughout Spain was assessed retrospectively. Data were collected from the medical records of patients over a period of 6 months following initiation of alemtuzumab therapy.

Effect of chemotherapy with alkylating agents on the yield of CD34+ cells in patients with multiple myeloma. Results of the Spanish Myeloma Group (GEM) Study.

Background And Objectives: Although alkylating agents are clearly beneficial in multiple myeloma (MM), their deleterious effect on bone marrow hematopoietic progenitor cells usually precludes their use as front-line therapy in patients scheduled to undergo autologous stem cell transplantation (ASCT). We analyzed the impact of first-line chemotherapy with alkylating agents on stem cell collection in MM patients.

Design And Methods: Seven hundred and eighty-nine patients included in the Spanish multicenter protocol GEM-2000 underwent mobilization therapy after four courses of alternating VBMCP/VBAD chemotherapy.