RESUMEN
BACKGROUND: Optimal consolidation for young patilents with relapsed/refractory (R/R) follicular lymphoma (FL) remains uncertain in the rituximab era, with an unclear benefit of autologous stem cell transplantation (ASCT). The multicenter, randomized, phase III FLAZ12 (NCT01827605) trial compared anti-CD20 radioimmunotherapy (RIT) with ASCT as consolidation after chemoimmunotherapy, both followed by rituximab maintenance. PATIENTS AND METHODS: Patients (age 18-65 years) with R/R FL and without significant comorbidities were enrolled and treated with three courses of conventional, investigator-chosen chemoimmunotherapies. Those experiencing at least a partial response were randomized 1 : 1 to ASCT or RIT before CD34+ collection, and all received postconsolidation rituximab maintenance. Progression-free survival (PFS) was the primary endpoint. The target sample size was 210 (105/group). RESULTS: Between August 2012 and September 2019, of 164 screened patients, 159 were enrolled [median age 57 (interquartile range 49-62) years, 55% male, 57% stage IV, 20% bulky disease]. The study was closed prematurely because of low accrual. Data were analyzed on 8 June 2023, on an intention-to-treat basis, with a 77-month median follow-up from enrollment. Of the 141 patients (89%), 70 were randomized to ASCT and 71 to RIT. The estimated 3-year PFS in both groups was 62% (hazard ratio 1.11, 95% confidence interval 0.69-1.80, P = 0.6662). The 3-year overall survival also was similar between the two groups. Rates of grade ≥3 hematological toxicity were 94% with ASCT versus 46% with RIT (P < 0.001), and grade ≥3 neutropenia occurred in 94% versus 41%, respectively (P < 0.001). Second cancers occurred in nine patients after ASCT and three after radioimmunotherapy (P = 0.189). CONCLUSIONS: Even if prematurely discontinued, our study did not demonstrate the superiority of ASCT versus RIT. ASCT was more toxic and demanding for patients and health services. Both strategies yielded similar, favorable long-term outcomes, suggesting that consolidation programs milder than ASCT require further investigation in R/R FL.
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Trasplante de Células Madre Hematopoyéticas , Linfoma Folicular , Humanos , Masculino , Persona de Mediana Edad , Adolescente , Adulto Joven , Adulto , Anciano , Femenino , Linfoma Folicular/radioterapia , Radioinmunoterapia , Rituximab , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Trasplante Autólogo , Trasplante de Células MadreRESUMEN
The study by Kambhampati et al. offers the first European perspective on cost-effectiveness of pola-R-CHP in the frontline line treatment of DLBCL patients. Nevertheless, the applicability of these results in other European settings remain questionable: Germany is indeed a wealthy country with wide access to cellular therapies in earlier lines, while this might not be the case for other European countries. The presented data must be re-assessed when long term data on PFS and OS from the POLARIX trial are available, ideally considering also real-life data. Similar CEAs in other European health care systems as well as in specific subgroups of patients are welcome to offer a broader perspective on the potential role of pola-R-CHP in Europe. Commentary on: Kambhampati et al. Cost effectiveness of polatuzumab vedotin in combination with chemoimmunotherapy (pola-R-CHP) in previously untreated diffuse large B-cell lymphoma in Germany. Br J Haematol 2023;202:771-775.
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Inmunoconjugados , Linfoma de Células B Grandes Difuso , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inmunoconjugados/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Inmunoterapia , Europa (Continente) , Alemania , Rituximab/uso terapéuticoRESUMEN
Background: Gene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Patients and methods: Here, we applied the computational method CIBERSORT to generate a 1028-gene matrix incorporating signatures of 17 immune and stromal cytotypes. Then, we carried out a deconvolution on publicly available GEP data of 482 untreated DLBCLs to reveal associations between clinical outcomes and proportions of putative tumor-infiltrating cell types. Forty-five genes related to peculiar prognostic cytotypes were selected and their expression digitally quantified by NanoString technology on a validation set of 175 formalin-fixed, paraffin-embedded DLBCLs from two randomized trials. Data from an unsupervised clustering analysis were used to build a model of clustering assignment, whose prognostic value was also assessed on an independent cohort of 40 cases. All tissue samples consisted of pretreatment biopsies of advanced-stage DLBCLs treated by comparable R-CHOP/R-CHOP-like regimens. Results: In silico analysis demonstrated that higher proportion of myofibroblasts (MFs), dendritic cells, and CD4+ T cells correlated with better outcomes and the expression of genes in our panel is associated with a risk of overall and progression-free survival. In a multivariate Cox model, the microenvironment genes retained high prognostic performance independently of the cell-of-origin (COO), and integration of the two prognosticators (COO + TME) improved survival prediction in both validation set and independent cohort. Moreover, the major contribution of MF-related genes to the panel and Gene Set Enrichment Analysis suggested a strong influence of extracellular matrix determinants in DLBCL biology. Conclusions: Our study identified new prognostic categories of DLBCL, providing an easy-to-apply gene panel that powerfully predicts patients' survival. Moreover, owing to its relationship with specific stromal and immune components, the panel may acquire a predictive relevance in clinical trials exploring new drugs with known impact on TME.
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Linfoma de Células B Grandes Difuso/mortalidad , Transcriptoma/genética , Microambiente Tumoral/genética , Adulto , Anciano , Algoritmos , Biopsia , Análisis por Conglomerados , Estudios de Cohortes , Biología Computacional , Conjuntos de Datos como Asunto , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Adhesión en Parafina , Valor Predictivo de las Pruebas , Pronóstico , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los Resultados , Análisis de Supervivencia , Adulto JovenRESUMEN
The majority of Hodgkin lymphoma patients are now cured with conventional first-line therapy; however, 10-15% of early-stage disease and less than 30% of advanced-stage patients are refractory(rare) or relapsed. Salvage second-line therapy combined with high-dose therapy and autologous stem-cell transplantation can cure 40-50% of patients. Recently novel agents (Brentuximab Vedotin and Immune Checkpoint inhibitors) have demonstrated evidence of therapeutic activity and are potential bridge to an allogeneic stem-cell transplantation. The review is aimed to present not only salvage strategies; indeed, the paper contains paragraphs about therapy and new treatment options at diagnosis.
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Antineoplásicos Inmunológicos/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , Inmunomodulación/efectos de los fármacos , Terapia Molecular Dirigida , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/efectos adversos , Bleomicina/uso terapéutico , Brentuximab Vedotina , Terapia Combinada , Dacarbazina/efectos adversos , Dacarbazina/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/mortalidad , Humanos , Inmunoconjugados/administración & dosificación , Inmunoconjugados/efectos adversos , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Retratamiento , Terapia Recuperativa , Resultado del Tratamiento , Vinblastina/efectos adversos , Vinblastina/uso terapéuticoRESUMEN
BACKGROUND: Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms. PATIENTS AND METHODS: This phase II study evaluated the response rate of copanlisib administered intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis. RESULTS: Thirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 and 8 weeks in the indolent and aggressive cohorts, respectively (overall range 2-138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range 0-874) and 70 days (range 0-897), respectively; median duration of response was 390 days (range 0-825) and 166 days (range 0-786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated phosphatidylinositol 3-kinase pathway gene expression. CONCLUSION: Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing. This trial is registered with ClinicalTrials.gov number NCT01660451 (Part A).
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Antineoplásicos/uso terapéutico , Linfoma/tratamiento farmacológico , Inhibidores de las Quinasa Fosfoinosítidos-3 , Pirimidinas/uso terapéutico , Quinazolinas/uso terapéutico , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Linfoma/metabolismo , Linfoma/patología , Masculino , Persona de Mediana Edad , Fosfohidrolasa PTEN/metabolismo , Pirimidinas/efectos adversos , Pirimidinas/farmacología , Quinazolinas/efectos adversos , Quinazolinas/farmacología , Recurrencia , Análisis de SupervivenciaRESUMEN
Lenalidomide is an oral non-chemotherapy immunomodulator with direct and indirect effects on non-Hodgkin lymphoma (NHL) cells and with single-agent activity in relapsed/refractory aggressive and indolent B-cell NHL, including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma, and follicular lymphoma. Based on the pivotal phase II MCL-001 trial of lenalidomide in heavily pretreated patients with relapsed/refractory MCL, lenalidomide was approved by the US Food and Drug Administration for the treatment of relapsed/refractory MCL after failure of two prior therapies, one of which includes bortezomib, at a recommended starting dose of 25 mg on days 1-21 of each 28-day cycle. Lenalidomide enhanced the survival benefit in combination with rituximab in preclinical models, prompting clinical evaluation of the lenalidomide-rituximab (R2) combination. In phase II trials, lenalidomide 20 mg on days 1-21 in combination with different standard-dose rituximab schedules exhibited promising activity in both first-line and relapsed/refractory disease across multiple B-cell NHL subtypes. The feasibility of combining lenalidomide with immunochemotherapy, including R-CHOP and rituximab-bendamustine, has been demonstrated in phase I/II trials. These latter regimens are currently being evaluated in ongoing phase II and III trials. The role of lenalidomide monotherapy and R2 in maintenance therapy is also being examined. Based on available evidence, a comprehensive review of lenalidomide in all treatment phases of B-cell NHL-relapsed/refractory disease, first-line, and maintenance-is presented here.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factores Inmunológicos/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células del Manto/tratamiento farmacológico , Talidomida/análogos & derivados , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Clorhidrato de Bendamustina/administración & dosificación , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Lenalidomida , Linfoma de Células B/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Prednisona/uso terapéutico , Rituximab/administración & dosificación , Talidomida/administración & dosificación , Talidomida/uso terapéutico , Resultado del Tratamiento , Vincristina/uso terapéuticoRESUMEN
To complete the existing treatment guidelines for all tumor types, ESMO organizes consensus conferences to better clarify open issues in each disease. In this setting, a consensus conference on the management of lymphoma was held on 18 June 2011 in Lugano, immediately after the end of the 11th International Conference on Malignant Lymphoma. The consensus conference convened â¼45 experts from all around Europe and selected six lymphoma entities to be addressed; for each of them three to five open questions were to be discussed by the experts. For each question, a recommendation should be given by the panel, supported by the strength of the recommendation based on the level of evidence. This consensus report focuses on the three most common lymphoproliferative malignancies: diffuse large B-cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia. A second report will concentrate on mantle cell lymphoma, marginal zone lymphoma and T-cell lymphomas.
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Leucemia Linfocítica Crónica de Células B/terapia , Linfoma Folicular/radioterapia , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Manejo de la Enfermedad , Humanos , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/patología , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/patología , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Guías de Práctica Clínica como Asunto , Trasplante de Células MadreRESUMEN
AIM: Objective of the study was to determine the most common cutaneous lesions in patients with haematologic malignancies observed at dermatologic consultation and to identify the impact parameters related to the haematologic condition, like disease type/duration, remission, chemotherapy and transplantation, have on skin manifestations. METHODS: A total of 101 consecutive patients with onco-haematological malignancies referred for dermatological consultation over a two-year period were included in this prospective single-centre observational cohort study. RESULTS: The most common finding was infection (19.8%), followed by drug adverse reactions (16.8%) and malignant neoplasia (11.9%). Elderly patients and those with a longer disease duration had a higher frequency of cutaneous neoplasia. Squamous cell carcinoma was the most frequent cutaneous neoplasia; three cases of melanoma were diagnosed and had a high Breslow thickness. Cutaneous involvement due to the haematological malignancies was observed in 5 patients. Common chronic dermatoses (psoriasis and eczema) were found in 10% of patients. Transplant had no effect on the percentage of infections or tumours. CONCLUSION: Patients with haematological malignancies have a higher incidence of adverse drug reactions with peculiar morphologic features and a lower incidence of common chronic dermatoses than patients referred for dermatological consultation by their general practitioner or other hospital services. Infectious dermatoses were less frequent than in solid organ transplanted patients. The complex variety of cutaneous lesions, the differential diagnostic pitfalls and the prognostic relevance of early skin tumour diagnosis, evidence the importance of a correct dermatological approach.
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Trasplante de Médula Ósea , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/cirugía , Enfermedades de la Piel/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/epidemiología , Estudios de Cohortes , Terapia Combinada , Comorbilidad , Erupciones por Medicamentos/epidemiología , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Estudios Prospectivos , Psoriasis/epidemiología , Derivación y Consulta , Enfermedades Cutáneas Infecciosas/epidemiología , Neoplasias Cutáneas/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The nuclear factor-kappa B activation in mucosa-associated lymphoid tissue (MALT) lymphoma pathogenesis provided the rationale for the evaluation of bortezomib in this malignancy. PATIENTS AND METHODS: Thirty-two patients with relapsed/refractory MALT lymphoma were enrolled. Thirty-one patients received bortezomib 1.3 mg/m(2) i.v., on days 1, 4, 8, and 11, for up to six 21-day cycles. RESULTS: Median age was 63 years (range, 37-82 years). Median number of prior therapies was 2 (range, 1-4). Nine patients had Ann Arbor stage I, 7 patients had stage II, and 16 patients had stage IV. Primary lymphoma localization was the stomach in 14 patients; multiple extranodal sites were present in 10 patients. Among the 29 patients assessable for response, the overall response rate was 48% [95% confidence interval (CI) 29% to 67%], with 9 complete and 5 partial responses. Nine patients experienced stable disease and six had disease progression during therapy. The most relevant adverse events were fatigue, thrombocytopenia, neutropenia, and peripheral neuropathy. After a median follow-up of 24 months, the median duration of response was not reached yet. Five deaths were reported, in two patients due to disease progression. CONCLUSION: Bortezomib is active in relapsed MALT lymphomas. Further investigations to identify optimal bortezomib dose, schedule, and combination regimens are needed since the frequent detection of dose-limiting peripheral neuropathy.
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Antineoplásicos/uso terapéutico , Ácidos Borónicos/uso terapéutico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Pirazinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Ácidos Borónicos/efectos adversos , Bortezomib , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B de la Zona Marginal/mortalidad , Masculino , Persona de Mediana Edad , Pirazinas/efectos adversos , Recurrencia , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: Ocrelizumab is a humanized anti-CD20 antibody with increased antibody-dependent cellular cytotoxicity compared with rituximab. This phase I/II study evaluated its safety and efficacy in patients with relapsed/refractory follicular lymphoma (FL) after prior rituximab therapy. DESIGN AND METHODS: Forty-seven patients were treated in three dose cohorts and received eight infusions every 3 weeks: cohort A, 200 mg/m(2) (n = 15); cohort B, 375 mg/m(2) (n = 16); cohort C, first dose 375 mg/m(2), seven subsequent doses of 750 mg/m(2) (n = 16). Patients were assessed for safety, efficacy, pharmacodynamics and pharmacokinetics. RESULTS: The median patient age was 58 years, the majority had Ann Arbor stage III/IV disease and had received a median of 2 (range 1-6) prior regimens. Ocrelizumab was well tolerated with grade 3/4 toxicity occurring in 9% of patients. The most common toxicity was infusion-related reactions (74% patients), all grade 1/2 except one grade 3 event. The objective response rate was 38% and was similar in patients with low-affinity and high-affinity variants of the Fcgamma receptor IIIa (FcgammaRIIIa). With follow-up of approximately 28 months, the median progression-free survival was 11.4 months. CONCLUSION: Ocrelizumab demonstrated activity in patients with relapsed/refractory FL following prior rituximab treatment, with safety similar to rituximab although adverse events appeared milder.
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Anticuerpos Monoclonales/uso terapéutico , Antígenos CD20/inmunología , Resistencia a Antineoplásicos/efectos de los fármacos , Linfoma Folicular/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Terapia Recuperativa , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados , Femenino , Estudios de Seguimiento , Humanos , Linfoma Folicular/inmunología , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Inducción de Remisión , Tasa de Supervivencia , Resultado del TratamientoAsunto(s)
Directrices para la Planificación en Salud , Linfoma Folicular/diagnóstico , Linfoma Folicular/terapia , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/terapia , Sociedades Médicas/normas , Terapia Combinada , Estudios de Seguimiento , Humanos , Estadificación de Neoplasias , PronósticoRESUMEN
Effective salvage options inducing high complete metabolic response (CMR) rates without significant toxicity are needed for Hodgkin lymphoma (HL) patients failing induction treatment and who are candidate to autologous stem cell transplantation (ASCT). Brentuximab vedotin (BV) and bendamustine are active monotherapies in the relapsed/refractory setting and their combination (the BBV regimen) possibly enhances their activity. This single-arm multicenter phase 2 study investigated the efficacy and safety of BBV as first salvage therapy in 40 patients with relapsed/refractory HL. Thirty-eight patients were evaluable for efficacy: 30 (78.9%) had a CMR and 2 (5.3%) a partial response, leading to an overall response rate (ORR) of 84.2%. The ORR in the primary refractory subset was 75.0%, among relapsed patients it was 94.4%. Thirty-five patients could mobilize peripheral blood stem cells and 33 underwent ASCT. At a median follow-up of 23 months, the estimated 3-year overall survival and progression-free survival are 88.1% and 67.3%. During therapy, only 3 grade IV cases of neutropenia occurred and resolved within a week. No grade 4 extrahematologic toxicities were reported; skin reactions were however rather frequent (65%). These results suggest that the BBV regimen exhibits promising efficacy and a manageable toxicity in a challenging subpopulation of HL patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina , Brentuximab Vedotina , Terapia Combinada , Femenino , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/mortalidad , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Terapia Recuperativa , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
Lenalidomide-RCHOP (R2-CHOP21) has been shown to be safe and effective in patients with untreated diffuse large B-cell lymphoma (DLBCL). The aim of this analysis is to report long-term outcome and toxicities in newly diagnosed DLBCL patients who received R2-CHOP21 in two independent phase 2 trials, conducted by Mayo Clinic (MC) and Fondazione Italiana Linfomi (FIL). All patients received R-CHOP21 plus lenalidomide. Long-term progression-free survival (PFS), time to progression (TTP), overall survival (OS) and late toxicities and second tumors were analyzed. Hundred and twelve patients (63 MC, 49 FIL) were included. Median age was 69 years, 88% were stage III-IV. At a median follow-up of 5.1 years, 5y-PFS was 63.5%, 5y-TTP 70.1% and 5y-OS 75.4%; according to cell of origin (COO): 5y-PFS 52.8% vs 64.5%, 5y-TTP 61.6% vs 69.6% and 5y-OS 68.6% vs 74.1% in germinal center (GCB) vs non-GCB respectively. Four patients experienced grade 4-5 late toxicities. Grade ≤ 3 toxicities were infections (N = 4), thrombosis (N = 1) and neuropathy (N = 3). Seven seconds tumors were observed. Long-term follow-up demonstrates that R2-CHOP21 efficacy was maintained with high rates of PFS, TTP, and OS. Lenalidomide appears to mitigate the negative prognosis of non-GCB phenotype. Incidence of therapy-related secondary malignancies and late toxicities were low.