Análisis multiparamétrico mediante citometría de flujo de las células plasmáticas de la médula ósea en pacientes con gammapatía monoclonal de significado incierto y mieloma quiescente: valor pronóstico e implicaciones clínicas

[EN]Characterized phenotypically and by DNA content cell compartment bone marrow plasma of patients with monoclonal gammopathy of undetermined significance and myeloma quiescent at the time of diagnosis, identifying and quantifying the CP phenotypically normal and pathological conditions. To assess the ability of the CMF multiparameter in predicting risk of progression to symptomatic MM in both MGUS and in the MQ. Compare the usefulness of multiparameter CMF in predicting risk of progression with prognostic factors described in the literature[ES]Caracterizar fenotípicamente y por contenido de ADN el compartimiento de células plasmática de la médula ósea de pacientes con gammapatía monoclonal de significado incierto y mielomas quiescentes en el momento del diagnóstico, identificando y cuantificando las CP fenotípicamente normales y patológicas. Valorar la capacidad de la CMF multiparamétrica en la predicción del riesgo de progresión a MM sintomático, tanto en las GMSI como en el MQ. Comparar la utilidad de la CMF multiparamétrica en la predicción del riesgo de progresión con los factores pronósticos descritos en la literatur

Geriatric assessment in hematology scale predicts treatment tolerability in older patients diagnosed with hematological malignancies: The RETROGAH study

Chemotherapy; Geriatric assessment; ToxicityQuimioterapia; Evaluación geriátrica; ToxicidadQuimioteràpia; Avaluació geriàtrica; ToxicitatIntroduction The GAH (Geriatric Assessment in Hematology) scale is a psychometrically valid tool aimed at identifying older patients with hematological malignancies at higher risk of treatment-related toxicity. Our objective in this study was to determine the weights for each dimension of the GAH scale and the cut-off point to reliably predict treatment tolerability in this population, estimated by a weighted receiver operating characteristic (ROC) analysis and quantified by the area under the curve (AUC). Material and Methods The RETROGAH was a retrospective cohort study including 126 patients who had previously participated in the GAH study. Patients were ≥ 65 years old with newly diagnosed myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), multiple myeloma (MM), or chronic lymphoid leukemia (CLL) and treated with standard front-line therapy within three months after having completed the GAH scale. Results The optimal cut-off value of the GAH total score to discriminate patients at higher risk of treatment toxicity was 42, with 68.5% sensitivity and 55.8% specificity. Using this value, 66.1% of patients evaluated were found to develop some type of toxicity. The AUC was 0.6259 (95% CI: 0.512–0.739; p = 0.035). Discussion The GAH scale not only would enable clinicians to individualize therapy based on individual risk of toxicity but also discriminate patients that will benefit most from intensive treatments from those requiring an adapted approach. While futures studies in clinical practice may improve the model and overcome its limitations, the GAH scale should not be used alone when making treatment decisions.This study was supported by Celgene España S.L

A glimpse into relapsed refractory multiple myeloma treatment in real-world practice in Spain: the GeminiS study

Relapsed-refractory multiple mieloma; Monoclonal antibodies; Observational multicenter studyMieloma múltiple recidivant-refractari; Anticossos monoclonals; Estudi observacional multicèntricMieloma múltiple recidivante-refractario; Anticuerpos monoclonales; Estudio multicéntrico observacionalObjectives: To describe the incorporation of monoclonal antibodies (mAb) in real-world (RW) practice for the treatment of patients with relapsed refractory multiple myeloma (RRMM) in a setting with other treatment alternatives. Methods: This was an observational, multicenter, ambispective study of RRMM treated with or without a mAb. Results: A total of 171 patients were included. For the group treated without mAb, the median (95% CI) progression-free survival (PFS) to relapse was 22.4 (17.8-27.0) months; partial response or better (≥PR) and complete response or better (≥CR) was observed in 74.1% and 24.1% of patients, respectively; and median time to first response in first relapse was 2.0 months and in second relapse was 2.5 months. For the group of patients treated with mAb in first or second relapse, the median PFS was 20.9 (95% CI, could not be evaluated) months; the ≥ PR and ≥ CR rates were 76,2% and 28.6%, respectively; and the median time to first response in first relapse was 1.2 month and in second relapse was 1.0 months. The safety profiles for the combinations were consistent with those expected. Conclusions: The incorporation of mAb in RW practice for the treatment of RRMM has shown good quality and speed of response with a similar safety profile shown in randomized clinical trials. Keywords: Relapsed-refractory multiple myeloma; daratumumab; monoclonal antibodies; real-world; standard of care

Safety of switching from intravenous to subcutaneous rituximab during first-line treatment of patients with non-Hodgkin lymphoma: the Spanish population of the MabRella study

Rituximab is a standard treatment for non-Hodgkin diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. A subcutaneous formulation was developed to improve the resource use of intravenous rituximab, with comparable efficacy and safety profiles except for increased administration-related reactions (ARRs). MabRella was a phase IIIb trial to assess the safety of switching from intravenous to subcutaneous administration of rituximab during first-line induction/maintenance for DLBCL or FL, focusing on ARRs. Efficacy, satisfaction and quality of life were also assessed. Patients received subcutaneous rituximab plus standard induction chemotherapy for DLBCL or FL for 4–7 cycles, and/or every 2 months maintenance monotherapy for FL for 6–12 cycles. The study included 140 patients: DLBCL, n = 29; FL, n = 111. Ninety-five percent of patients experienced adverse events, reaching grade ≥3 in 38 6% and were serious in 30 0%. AARs occurred in 48 6%, mostly (84 9%) at the injection site, with only 2 1% of patients reaching grade 3. The end-of-induction complete/unconfirmed complete response rate was 69 6%. After a median follow-up of 33 5 months, median disease-/event-/progression-free and overall survivals were not attained. The Rituximab Administration Satisfaction Questionnaire showed improvements in overall satisfaction and the EuroQoL-5D a good quality-of-life perception at induction/maintenance end. Therefore, switching to subcutaneous rituximab showed no new safety issues and maintained efficacy with improved satisfaction and quality of life

Genomic mutation profile in progressive chronic lymphocytic leukemia patients prior to first-line chemoimmunotherapy with FCR and rituximab maintenance (REM)

Chronic Lymphocytic Leukemia (CLL) is the most prevalent leukemia in Western countries and is notable for its variable clinical course. This variability is partly reflected by the mutational status of IGHV genes. Many CLL samples have been studied in recent years by next-generation sequencing. These studies have identified recurrent somatic mutations in NOTCH1, SF3B1, ATM, TP53, BIRC3 and others genes that play roles in cell cycle, DNA repair, RNA metabolism and splicing. In this study, we have taken a deep-targeted massive sequencing approach to analyze the impact of mutations in the most frequently mutated genes in patients with CLL enrolled in the REM (rituximab en mantenimiento) clinical trial. The mutational status of our patients with CLL, except for the TP53 gene, does not seem to affect the good results obtained with maintenance therapy with rituximab after front-line FCR treatment

Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial

Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0-54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3-4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ?CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene

Safety of switching from intravenous to subcutaneous rituximab during first-line treatment of patients with non-Hodgkin lymphoma: the Spanish population of the MabRella study.

Rituximab is a standard treatment for non-Hodgkin diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. A subcutaneous formulation was developed to improve the resource use of intravenous rituximab, with comparable efficacy and safety profiles except for increased administration-related reactions (ARRs). MabRella was a phase IIIb trial to assess the safety of switching from intravenous to subcutaneous administration of rituximab during first-line induction/maintenance for DLBCL or FL, focusing on ARRs. Efficacy, satisfaction and quality of life were also assessed. Patients received subcutaneous rituximab plus standard induction chemotherapy for DLBCL or FL for 4-7 cycles, and/or every 2 months maintenance monotherapy for FL for 6-12 cycles. The study included 140 patients: DLBCL, n = 29; FL, n = 111. Ninety-five percent of patients experienced adverse events, reaching grade ≥3 in 38·6% and were serious in 30·0%. AARs occurred in 48·6%, mostly (84·9%) at the injection site, with only 2·1% of patients reaching grade 3. The end-of-induction complete/unconfirmed complete response rate was 69·6%. After a median follow-up of 33·5 months, median disease-/event-/progression-free and overall survivals were not attained. The Rituximab Administration Satisfaction Questionnaire showed improvements in overall satisfaction and the EuroQoL-5D a good quality-of-life perception at induction/maintenance end. Therefore, switching to subcutaneous rituximab showed no new safety issues and maintained efficacy with improved satisfaction and quality of life

Safety of switching from intravenous to subcutaneous rituximab during first-line treatment of patients with non-Hodgkin lymphoma: the Spanish population of the MabRella study

Rituximab is a standard treatment for non-Hodgkin diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. A subcutaneous formulation was developed to improve the resource use of intravenous rituximab, with comparable efficacy and safety profiles except for increased administration-related reactions (ARRs). MabRella was a phase IIIb trial to assess the safety of switching from intravenous to subcutaneous administration of rituximab during first-line induction/maintenance for DLBCL or FL, focusing on ARRs. Efficacy, satisfaction and quality of life were also assessed. Patients received subcutaneous rituximab plus standard induction chemotherapy for DLBCL or FL for 4–7 cycles, and/or every 2 months maintenance monotherapy for FL for 6–12 cycles. The study included 140 patients: DLBCL, n = 29; FL, n = 111. Ninety-five percent of patients experienced adverse events, reaching grade ≥3 in 38 6% and were serious in 30 0%. AARs occurred in 48 6%, mostly (84 9%) at the injection site, with only 2 1% of patients reaching grade 3. The end-of-induction complete/unconfirmed complete response rate was 69 6%. After a median follow-up of 33 5 months, median disease-/event-/progression-free and overall survivals were not attained. The Rituximab Administration Satisfaction Questionnaire showed improvements in overall satisfaction and the EuroQoL-5D a good quality-of-life perception at induction/maintenance end. Therefore, switching to subcutaneous rituximab showed no new safety issues and maintained efficacy with improved satisfaction and quality of life

Real-world characteristics and outcome of patients treated with single-agent ibrutinib for chronic lymphocytic leukemia in Spain (IBRORS-LLC Study)

Background: Ibrutinib demonstrated remarkable efficacy and favorable tolerability in patients with untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including those with high-risk genetic alterations. The IBRORS-CLL study assessed the characteristics, clinical management and outcome of CLL patients receiving ibrutinib in routine clinical practice in Spain. Patients: Observational, retrospective, multicenter study in CLL patients who started single-agent ibrutinib as first-line treatment or at first or second relapse between January 2016 and January 2019. Results: A total of 269 patients were included (median age: 70.9 years; cardiovascular comorbidity: 55.4%, including hypertension [47.6%] and atrial fibrillation [AF] [7.1%]). Overall, 96.7% and 69% of patients underwent molecular testing for del(17p)/TP53 mutation and IGHV mutation status. High-risk genetic features included unmutated IGHV (79%) and del(17p)/TP53 mutation (first-line: 66.3%; second-line: 23.1%). Overall, 84 (31.2%) patients received ibrutinib as first-line treatment, and it was used as second- and third-line therapy in 121 (45.0%) and 64 (23.8%) patients. The median progression-free survival and overall survival were not reached irrespective of del(17p)/TP53, or unmutated IGHV. Common grade ≥3 adverse events were infections (12.2%) and bleeding (3%). Grade ≥3 AF occurred in 1.5% of patients. Conclusion: This real-world study shows that single-agent ibrutinib is an effective therapy for CLL, regardless of age and high-risk molecular features, consistent with clinical trials. Additionally, single-agent ibrutinib was well tolerated, with a low rate of cardiovascular events. This study also emphasized a high molecular testing rate of del(17p)/TP53 mutation and IGHV mutation status in clinical practice according to guideline recommendations