Prognostic risk and survival of asymptomatic IgM monoclonal gammopathy: Results from a Spanish Multicenter Registry.

Asymptomatic IgM gammopathy encompasses IgM monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic Waldenström macroglobulinemia (AWM), both having a risk of progression to symptomatic disease. Here, we assessed the risk of progression and the mortality of 956 patients with asymptomatic IgM gammopathy across 25 Spanish centers. After a median follow-up of 5.

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.

Phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma.

Previous studies showed antitumor activity for plitidepsin plus dexamethasone (DXM) in relapsed/refractory multiple myeloma (r/r MM), and in vitro synergism with bortezomib (BTZ) or DXM against MM cells. This phase I trial evaluated plitidepsin (3-h intravenous infusion Day 1 and 15), BTZ (subcutaneous bolus Day 1, 4, 8, and 11), and DXM (orally Day 1, 8, 15, and 22), every 4 weeks in 36 r/r MM patients. Twenty-two patients were treated using a standard dose escalation design (10 at the recommended dose [RD] cohort), and 14 additional patients were treated to expand the RD cohort.

Real-World Evidence of Daratumumab Monotherapy in Relapsed/Refractory Multiple Myeloma Patients and Efficacy on Soft-Tissue Plasmacytomas.

Introduction: Daratumumab is an anti-CD38 agent that was first investigated as single agent in GEN501 and SIRIUS trials in patients with advanced multiple myeloma (MM). Overall response rate (ORR) was 30% with positive impact on progression-free survival (PFS). However, there is a lack of information regarding plasmacytoma response.

Lupus anticoagulant is an independent risk factor for non-thrombotic in-hospital mortality in COVID-19 patients.

Background: Thromboembolic disease is a frequent cause of death during SARS CoV-2 infection. Lupus anticoagulant (LA) appears frequently during the acute phase of infection. It is not clear whether it is merely an epiphenomenon or whether it is related to the patients' outcome.

Predictors of return to work after autologous stem cell transplantation in patients with multiple myeloma.

Return to work (RTW) is a marker of functional recovery in cancer patients, with quality of life, financial and social implications. We investigated frequency and factors associated with RTW in a cohort of patients younger than 66 years, with newly diagnosed multiple myeloma (MM), uniformly treated with a bortezomib-based induction followed by autologous stem cell transplantation (ASCT). Socio-economic and working status data were collected by a self-administered questionnaire.

Treatment patterns and outcomes in real-world transplant-ineligible patients newly diagnosed with multiple myeloma.

Despite the significant proportion of older patients with newly diagnosed multiple myeloma (MM), most clinical trials driving therapeutic decisions in routine practice include younger and presumably healthier patients than those in the real world. Furthermore, longitudinal studies suggest that elderly, transplant-ineligible patients with MM are not benefitting enough from new anti-MM agents. We retrospectively analyzed the profile of and treatment patterns and outcomes in 675 transplant-ineligible patients with MM who started frontline therapy in routine practice.

Pomalidomide, Cyclophosphamide, and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma: Real-World Analysis of the Pethema-GEM Experience.

Introduction: Treatment of relapsed/refractory multiple myeloma (RRMM) is highly challenging, especially for patients with disease refractory to initial therapy, and in particular for disease developing refractoriness to lenalidomide. Indeed, with currently approved treatments, median progression-free survival (PFS) in the lenalidomide-refractory setting is less than 10 months, reflecting the difficulty in treating this patient population. Pomalidomide is a second-generation immunomodulatory drug that has shown activity in lenalidomide-refractory disease in the setting of different combinations.

Impact of response to treatment in health-related quality of life patient-reported outcomes in elderly patients with relapsed multiple myeloma.

Multiple myeloma (MM) is a recurrent malignancy with a high impact on quality of life. Improved survival relies on the combination of drugs and extended duration of therapy, raising concerns on its toxicity burden in elderly patients. Health-related quality of life measurements attent to capture health aspects relevant to patients other than efficacy.

Clinical outcome and prognostic factors of patients with Richter syndrome: real-world study of the Spanish Chronic Lymphocytic Leukemia Study Group (GELLC).

Richter syndrome (RS) is an uncommon evolution of chronic lymphocytic leukaemia (CLL) with a dismal prognosis. Clinical-biological features predicting outcome and best therapeutic approach for these patients remain to be established. In this study, 128 patients with RS, including 112 diffuse large B-cell lymphoma (DLBCL)-type RS, 15 Hodgkin lymphoma (HL)-type RS, and one plasmablastic lymphoma, were identified in 11 centres of the Spanish CLL Study Group (GELLC).

Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group.

This phase I/II trial evaluated the combination of the kinesin spindle protein inhibitor filanesib with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma (RRMM) patients. Forty-seven RRMM patients with a median of three prior lines (2-8) and 94% refractory to lenalidomide were included: 14 in phase I and 33 in phase II. The recommended dose was 1·25 mg/m of filanesib on days 1, 2, 15, 16, with pomalidomide 4 mg on days 1-21 and dexamethasone 40 mg weekly.

Response to First Cycle Is the Major Predictor of Long-Term Response to Lenalidomide and Dexamethasone Therapy in Relapsed and Refractory Multiple Myeloma: Can We Spare Patients the Toxicity and Costs of Additional Agents?

Background: Lenalidomide plus dexamethasone (Ld) is still considered an option of care for some selected patients with relapsed or refractory multiple myeloma (RRMM), despite the proven superiority of lenalidomide-based triplet therapy. Up to 20% of patients obtain long-term benefit from Ld alone. The aim of this multicenter retrospective study was to identify and characterize those with good response to Ld salvage therapy, defined as progression-free survival lasting more than 24 months.

Frequency and prognostic significance of additional cytogenetic abnormalities to the Philadelphia chromosome in young and older adults with acute lymphoblastic leukemia.

About 25-35% of adult patients with acute lymphoblastic leukemia show the Philadelphia (Ph) chromosome. Few series have evaluated the prognosis of additional cytogenetic alterations (ACA) to the Ph chromosome. We analyzed the frequency, type and prognostic significance ofACA in adults (18-60 years) treated in the ALL-Ph-08 trial.

Impact of induction treatment before autologous stem cell transplantation on long-term outcome in patients with newly diagnosed multiple myeloma.

Objective: Clinical trials for patients with multiple myeloma (MM) using novel agent (NA)-based regimens before autologous stem cell transplantation (SCT) have shown improvement in response rates and progression-free survival (PFS); however they have failed to identify a significant overall survival (OS) benefit. The aim of this study was to analyze the potential impact of initial induction on the feasibility and outcome of subsequent treatment lines in a real clinical practice setting.

Methods: Patients with consecutive MM <70 years of age diagnosed between 1999 and 2009 were prospectively registered and classified as having received conventional chemotherapy induction regimens with new agents available at relapse (CC cohort, 89 patients) or as treated with NAs upfront (NA cohort, 65 patients).

Refractoriness to immunochemotherapy in follicular lymphoma: Predictive factors and outcome.

Follicular lymphoma is characterized by a good response to immunochemotherapy (ICT). However, a small percentage of patients responds poorly to treatment and seems to have a worse outcome. This study attempted to identify the predictive factors and outcome of refractoriness to first-line ICT.

Relapse risk after autologous stem cell transplantation in patients with lymphoma based on CD34+ cell dose.

It is unclear whether higher CD34 + cell doses infused for ASCT have any influence on survival or relapse in patients with lymphoma. We analyzed the correlation of infused CD34 + cell dose with relapse, survival, and hematopoietic recovery in 146 consecutive patients undergoing ASCT for lymphoma. Higher doses (>5 × 10/kg) were significantly correlated with earlier hematopoietic recovery, fewer infectious episodes, lower transfusion needs.

New drugs for follicular lymphoma.

Despite the improvement in prognosis since the advent of rituximab, follicular lymphoma is still incurable and remains the cause of death of most afflicted patients. With the expanding knowledge of the pathogenesis of B-cell malignancies, in the last few years a plethora of new therapies acting through a variety of mechanisms have shown promising results. This review attempts to analyze the evidence available on these new drugs, which include new monoclonal antibodies and immunoconjugates, the anti-angiogenic and immunomodulatory agent lenalidomide, the proteasome inhibitor bortezomib, inhibitors of B-cell receptor pathway enzymes, such as ibrutinib, idelalisib, duvelisib and entospletinib, BCL2 inhibitors and checkpoint inhibitors.

Frequency and prognostic significance of t(v;11q23)/KMT2A rearrangements in adult patients with acute lymphoblastic leukemia treated with risk-adapted protocols.

The karyotype is an important predictor of outcome in acute lymphoblastic leukemia (ALL). Rearrangements of the 11q23 region involving the KMT2A gene confer an unfavorable prognosis. Forty-six adult ALL patients from the PETHEMA Group treated with risk-adapted protocols, with t(v;11q23) were selected for this study.

The long term follow-up of early stage follicular lymphoma treated with radiotherapy, chemotherapy or combined modality treatment.

Local (involved-field or recently involved-site) radiotherapy is the standard therapy in limited-stage follicular lymphoma (FL). We retrospectively analyzed the value of chemotherapy in 130 patients with limited-stage FL (46 treated with radiotherapy alone [RT group], 30 with radiotherapy plus chemotherapy [COMBINED group] and 43 with chemotherapy alone [CHEMO group], 11 were managed with observation). Ninety-six percent of patients responded (RT 98%, COMBINED 100%, CHEMO 91%, p=0.

Prognostic significance of complex karyotype and monosomal karyotype in adult patients with acute lymphoblastic leukemia treated with risk-adapted protocols.

Background: The karyotype is a predictor of outcomes in adults with acute lymphoblastic leukemia (ALL). The unfavorable prognostic significance of complex karyotype (CK) has been reported, whereas the prognostic relevance of monosomal karyotype (MK) has not been consistently evaluated. We aimed to assess the prognostic value of CK and MK in adults with ALL treated with risk-adapted protocols of the Spanish PETHEMA Group.

[New drugs in the treatment of multiple myeloma].

Progress in the treatment of multiple myeloma in the last decade has been able to delay, but ultimately not to prevent, the development of resistances and most patients still die of the disease or its related complications. New drugs have been developed including new alkylating agents, proteasome inhibitors and immunomodulators but also monoclonal antibodies and drugs with new mechanisms of action. Hopefully, this new generation of targeted agents will improve the results of the initial therapy, avoid relapses and development of resistances and provide better and less toxic options for the relapsed and refractory patient.

Mobilization and engraftment of peripheral blood stem cells in healthy related donors >55 years old.

Background Aims: The increasing scarcity of young related donors has led to the use of older donors for related allogeneic hematopoietic stem cell transplantation (HSCT). This study analyzed the influence of age on the results of mobilization of peripheral blood stem cells (PBSCs) in healthy donors as well as on the engraftment and outcome of HSCT.

Methods: A retrospective analysis from a single center was performed comparing the results of PBSC mobilization from related healthy donors according to their age.