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Background: SMZL is a relatively rare low grade B-cell lymphoma, characterized usually by an indolent clinical behavior. Since there is no prospective randomized trials to establish the best treatment approach, decision on therapeutic management should be based on the available retrospective series. Based on these data, rituximab and splenectomy appear to be the most effective. Splenectomy represented the standard treatment modality until early 2000s. More than 90% of the patients present quick amelioration of splenomegaly related symptoms along with improvement of cytopenias related to hypersplenism. The median progression free survival was 8.25 years in the largest series of patients published so far, while the median 5- and 10- year OS were 84% and 67%, respectively. Responses to splenectomy are not complete since extrasplenic disease persists. Patients with heavy bone marrow infiltration, lymphadenopathy or other disease localization besides the spleen are not good candidates for splenectomy. Furthermore splenectomy is a major surgical procedure accompanied by acute perioperative complications as well as late toxicities mainly due to infections. For that reasons splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk. On the other hand rituximab monotherapy displays high efficacy with minimal toxicity. Several published series have shown an ORR more than 90%, with high CR rates (∼50%). The 10-year PFS and OS were 63% and 85%, respectively in a series of 104 SMZL patients. The role of rituximab maintenance has been investigated by only one group. Based on these data, maintenance with rituximab further improved the quality of responses by increasing significantly the CR rates (from 42% at the end of induction to 71% at the end of maintenance treatment), as well as the duration of responses: 7-year PFS was 75% for those patients who received maintenance vs 39% for those who did not (p < 0.0004). However no difference in OS has been noticed between the two groups, so far. Summarizing the above data, it is obvious that Rituximab monotherapy is associated with high response rates, long response duration and favorable safety profile, rendering it as the treatment of choice in SMZL., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Splenic marginal zone lymphoma (SMZL) is a distinct lymphoma entity characterized by an indolent clinical course and prolonged survival. Treatment is not standardized, since there are no prospective randomized trials in large series of SMZL patients. Splenectomy and rituximab represent the most effective treatment strategies used so far. The addition of chemotherapy to rituximab has not further improved the outcome, although this issue requires further investigation. Rituximab monotherapy has been associated with high response rates (∼90%), with approximately half of these responses being complete, even at the molecular level. More importantly, many of these responses are long-lasting, with a reported 7-year progression-free survival (PFS) at the rate of 69%. Maintenance rituximab treatment has been associated with further improvement of the quality of response as well as longer response duration in studies derived from one group of investigators. Based on its high efficacy and the good safety profile, rituximab represent one of the best treatment options for SMZL patients. Moreover, rituximab retains its efficacy in the relapse setting in most cases. Splenectomy is a meaningful alternative to rituximab in patients with bulky splenomegaly and cytopenias, without extensive bone marrow infiltration, who are fit for surgery. However splenectomy cannot completely eradicate the disease and it is also associated with greater morbidity or even mortality compared to rituximab. The choice of one of these two treatment approaches (rituximab or splenectomy) should mainly be based on patient's characteristics and on the disease burden. Novel agents are currently testing in low grade lymphomas including a small number of SMZL patients with promising results., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Central nervous system (CNS) involvement is rare in primary mediastinal large B‐cell lymphoma (PMLBCL). We aimed to evaluate the incidence of CNS relapse as first treatment failure event and the effect of the induction chemotherapy regimen, central nervous system ‐ international prognostic index (CNS‐IPI) and other clinical and laboratory variables on the risk of CNS relapse in 564 PMLBCL patients treated with immunochemotherapy. Only 17 patients (3.0%) received CNS prophylaxis. During a 55‐month median follow‐up only 8 patients experienced CNS relapse as first event, always isolated. The 2‐year cumulative incidence of CNS relapse (CI‐CNSR) was 1.47% and remained unchanged thereafter. The CI‐CNSR was not affected by the chemotherapy regimen (R‐CHOP or R‐da‐EPOCH). None of the established International Prognostic Index factors for aggressive lymphomas predicted CNS relapse in PMLBCL. The 2‐year CI‐CNSR in patients with versus without kidney involvement was 13.3% versus 0.96% (p < 0.001); 14.3% versus 1.13% with versus without adrenal involvement (p < 0.001); and 10.2% versus 0.97% with versus without either kidney or adrenal involvement. CNS‐IPI was also predictive (2‐year CI‐CNSR in high‐risk vs. intermediate/low‐risk: 10.37% vs. 0.84%, p < 0.001). However, this association may be driven mainly by kidney and/or adrenal involvement. In conclusion, in PMLBCL, CNS relapse is rare and appears to be strongly associated with kidney and/or adrenal involvement. [ABSTRACT FROM AUTHOR]

Simple Summary: Diffuse large B-cell lymphoma (DLBCL) is the most common high-grade non-Hodgkin lymphoma. The current treatment combining the anti-CD20 monoclonal antibody rituximab with chemotherapy is the gold standard for frontline treatment. Although the results for patients who relapse had been disappointing, the recent research explosion on novel agents for DLBCL has reignited the hope for these patients. This review aims to summarize the exciting research results of novel therapeutic agents recently approved or under investigation for the treatment of DLBCL. We focus on novel monoclonal antibodies conjugated to cytotoxic drugs and bispecific antibodies that have shown very promising results for patients in the relapsed/refractory setting. Although rituximab has revolutionized the treatment of diffuse large B-cell lymphoma (DLBCL), a significant proportion of patients experience refractory disease or relapse early after the end of treatment. The lack of effective treatment options in the relapsed/refractory (R/R) setting had made the prognosis of these patients dismal. The initial enthusiasm for novel anti-CD20 antibodies had been short-lived as they failed to prove their superiority to rituximab. Therefore, research has focused on developing novel agents with a unique mechanism of action. Among them, two antibody-drug conjugates, namely polatuzumab vedotin (PolaV) and loncastuximab tesirine, along with tafasitamab, an anti-CD19 bioengineered antibody, have been approved for the treatment of R/R DLBCL. Whereas PolaV has been FDA and EMA approved, EMA has not approved loncastuximab tesirine and tafasitamab yet. Results from randomized trials, as well as real-life data for PolaV have been promising. Novel agents as bispecific antibodies bridging CD3 on T-cells to CD20 have shown very promising results in clinical trials and are expected to gain approval for treatment of R/R DLBCL soon. As the therapeutic armamentarium against DLBCL is expanding, an improvement in survival of patients with R/R and higher cure rates might soon become evident. [ABSTRACT FROM AUTHOR]

Background: R‐CHOP can cure approximately 75% of patients with primary mediastinal large B‐cell lymphoma (PMLBCL), but prognostic factors have not been sufficiently evaluated yet. R‐da‐ EPOCH is potentially more effective but also more toxic than R‐CHOP. Reliable prognostic classification is needed to guide treatment decisions. Materials and Methods: We analyzed the impact of clinical prognostic factors on the outcome of 332 PMLBCL patients ≤65 years treated with R‐CHOP ± radiotherapy in a multicenter setting in Greece and Cyprus. Results: With a median follow‐up of 69 months, 5‐year freedom from progression (FFP) was 78% and 5‐year lymphoma specific survival (LSS) was 89%. On multivariate analysis, extranodal involvement (E/IV) and lactate dehydrogenase (LDH) ≥2 times upper limit of normal (model A) were significantly associated with FFP; E/IV and bulky disease (model B) were associated with LSS. Both models performed better than the International Prognostic Index (IPI) and the age‐adjusted IPI by Harrel's C rank parameter and Akaike information criterion. Both models A and B defined high‐risk subgroups (13%–27% of patients [pts]) with approximately 19%–23% lymphoma‐related mortality. They also defined subgroups composing approximately one‐fourth or one‐half of the patients, with 11% risk of failure and only 1% or 4% 5‐year lymphoma‐related mortality. Conclusion: The combination of E/IV with either bulky disease or LDH ≥2 times upper limit of normal defined high‐risk but not very‐high‐risk subgroups. More importantly, their absence defined subgroups comprising approximately one‐fourth or one‐half of the pts, with 11% risk of failure and minimal lymphoma‐related mortality, who may not need more intensive treatment such as R‐da‐EPOCH. Implications for Practice: By analyzing the impact of baseline clinical characteristics on outcomes of a large cohort of patients with primary mediastinal large B‐cell lymphoma homogeneously treated with R‐CHOP with or without radiotherapy, we developed novel prognostic indices which can aid in deciding which patients can be adequately treated with R‐CHOP and do not need more intensive regimens such as R‐da‐EPOCH. The new indices consist of objectively determined characteristics (extranodal disease or stage IV, bulky disease, and markedly elevated serum lactate dehydrogenase), which are readily available from standard initial staging procedures and offer better discrimination compared with established risk scores (International Prognostic Index [IPI] and age‐adjusted IPI). This article presents data on a large number of patients with primary mediastinal (thymic) large B‐cell lymphoma and reports a powerful prognostic factor analysis to identify high‐ or low‐risk risk subgroups for risk‐adapted therapy. [ABSTRACT FROM AUTHOR]

Splenic marginal zone lymphoma (SMZL) is a rare chronic B-cell lymphoproliferative disorder recognized as a distinct entity in the World Health Organization (WHO) classification. SMZL usually runs an indolent clinical course with a median survival of more than 10 years. However, in a proportion of patients (10-20%) SMZL behaves more aggressively, with a median survival of less than 4 years. Many efforts are ongoing to establish commonly accepted prognostic factors as a guide to therapy for this disorder. Data on the treatment of SMZL come from reported retrospective series including relatively limited numbers of patients. Despite these limitations, much progress has recently been made in the management of patients with SMZL. The oldest and most commonly used first-line therapeutic modality is splenectomy, which offers rapid alleviation of splenomegaly-related symptoms along with an improvement of cytopenias in the majority of patients, with a median PFS of 5 years. However, SMZL is a systemic disease, and splenectomy is not carried out with eradicative intent. Furthermore, splenectomy is a major surgical procedure with significant morbidity or even mortality, especially in older patients. Chemotherapy has only moderate activity in this form of MZL. Recent data suggest that rituximab is a very effective therapy with minimal toxicity and could replace splenectomy as first-line treatment. The overall response rate is > 90%, with almost half of responses being complete, while the 5-year progression-free survival is approximately 70%. The combination of rituximab with chemotherapy requires further evaluation. Based on the current data, splenectomy could be abandoned as first-line treatment for patients with SMZL. [ABSTRACT FROM AUTHOR]

Background. Treatment of splenic marginal zone lymphoma (SMZL) patients is not standardized. Recent data suggest that rituximab is highly effective and could be considered as initial therapy. Aim. To assess the efficacy of rituximab monotherapy in a large series of patients with SMZL and compare these results with splenectomy results. Methods. The studied population included 85 patients. Fifty-eight received rituximab at a dose of 375 mg/m2 per week for 6 weeks as induction followed by maintenance at the same dose every 2 months for 1-2 years, whereas 27 patients were treated using splenectomy only. Results. The overall response rate to rituximab 2 months after the end of induction was 95% (complete response [CR], 45%; unconfirmed CR, 26%; partial response, 24%). The median times to hematologic and clinical response were2weeks and3 weeks, respectively. Forty-three of 55 patients already completed the maintenance phase: 28 sustained their initial response, 14 improved their response, and one progressed. Eighty-five percent of splenectomized patients responded, and two were treated with rituximab as consolidation after splenectomy and achieved a CR. The 5-year overall and progression- free survival (PFS) rates for rituximab-treated and splenectomized patients were 92% and 77% (p = .09) and 73% and 58% (p = .06), respectively. Furthermore, maintenance therapy with rituximab resulted in a longer duration of response (at 5 years, PFS was 84% for patients receiving maintenance and 36% for patients without maintenance, p<.0001). Conclusions. Rituximab is a very effective and well-tolerated therapy and may be substituted for splenectomy as the first line treatment of choice for patients with SMZL. [ABSTRACT FROM AUTHOR]

More aggressive treatment approaches (methotrexate, cytarabine, cyclophosphamide, vincristine, prednisone, and bleomycin [the MACOP-B regimen] or consolidation with high-dose therapy and autologous stem cell transplantation) have been considered to be superior to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with primary mediastinal large B-cell lymphoma (PMLBCL). Rituximab-CHOP (R-CHOP) is the standard of care for diffuse large B-cell lymphoma, whereas efficacy in PMLBCL has not been adequately confirmed. Patient and Methods. Seventy-six consecutive PMLBCL patients who received R-CHOP with or without radiotherapy (RT) were compared with 45 consecutive historical controls treated with CHOP with or without RT. Baseline characteristics of the two groups were balanced. Results. The rate of early treatment failure was much lower with R-CHOP with or without RT (9% versus 30%; p = .004). The 5-year freedom from progression rate after R-CHOP with or without RT was 81%, versus 48% for CHOP with or without RT (p < .0001). The 5-year event-free survival rates were 80% and 47% (p < .0001) and the 5-year overall and lymphoma-specific survival rates were 89% and 69% (p = .003) and 91% and 69% (p = .001), respectively, with only seven of 76 lymphoma-related deaths. Among R-CHOP responders, 52 of 68 received RT. Conclusions. Based on these results, most patients with PMLBCL appear to be cured by R-CHOP in 21-day cycles with or without RT, which could be the current standard of care. Therefore, the need for more aggressive treatment strategies is questionable unless high-risk patients are adequately defined. Further studies are required to establish the precise role of RT. [ABSTRACT FROM AUTHOR]

The optimal treatment approach for patients with mantle cell lymphoma (MCL) is not well defined. Intensive therapeutic regimens result in high response rates and prolonged progression-free survival but at the expense of significant toxicity. We report here our results of the administration of rituximab plus chlorambucil (R-Chl) as first line treatment in patients with MCL. Twenty consecutively diagnosed patients were treated with this combination in which an induction and a maintenance arm were included. During induction, rituximab was administered at a dose of 375 mg/m2 on day 1, while chlorambucil was given afterward at a dose of 10 mg/day for 10 consecutive days for eight cycles and then as a single agent for an additional four cycles. Maintenance consisted of rituximab administration every 2 months for 1 year. Most patients had indolent disease features such as a low mantle-cell international prognostic index (MIPI) score. The overall response rate was 95% (90% CR, 5% PR). Among patients in CR, 78% presented a molecular remission. The 3-year progression-free survival was 89%. There were no serious side effects. These results show that the R-Chl combination could be an effective therapeutic option as first line treatment in MCL, especially for patients with indolent disease characteristics. [ABSTRACT FROM AUTHOR]

Primary cutaneous marginal zone lymphoma (PCMZL) is an indolent disease. Treatment options include excision, local irradiation, interferon- α or chemotherapy. We present two patients with PCMZL and multiple skin lesions successfully treated with intralesional administration of the anti-CD20 monoclonal antibody rituximab. The first presented with four red skin lesions and the second with two. Biopsy of the largest lesion revealed marginal zone B-cell lymphoma in both patients. There was no evidence of systemic involvement in either patient. Both patients were treated with intralesional rituximab for 18 consecutive weeks. Skin lesions gradually regressed. Apart from mild local pain during the injection, no other adverse effects were observed. In conclusion, rituximab can be safely administered intralesionally in patients with PCMZL and can produce disease remission. [ABSTRACT FROM AUTHOR]

Assesses different treatment strategies for indolent lymphomas. Use of chemotherapy based treatment when the patient develops constitutional symptoms or symptoms related to tumor burden; Treatment of elderly patients with oral alkylating agents; Production of superior progression free survival rates by adding rituximab to conventional chemotherapy.

Simple Summary: The urgency of the COVID-19 pandemic has led to accelerated vaccine development within less than a year. Emerging data suggest that the ability of patients with hematological malignancies to form an adequate number of antibodies in response to vaccination for SARS-CoV-2 is suboptimal. In this context, we evaluated the ability of 132 patients with Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma and Hodgkin's Lymphoma to elicit an adequate immune response to the BNT162b2 vaccine. Vaccination with two doses of the BNT162b2 vaccine led to lower production of neutralizing antibodies against SARS-CoV-2 in these patients compared with healthy controls. Being on active treatment for the underlying disease was an independent prognostic factor for suboptimal antibody response. This finding underlines the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures. Emerging data suggest suboptimal antibody responses to COVID-19 vaccination in patients with hematological malignancies. We evaluated the humoral response following the BNT162b2 vaccine in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). An FDA-approved, ELISA-based methodology was implemented to evaluate the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 on day 1 of the first vaccine, and afterwards on day 22 and 50. One hundred and thirty-two patients with CLL/lymphomas and 214 healthy matched controls vaccinated during the same period, at the same center were enrolled in the study (NCT04743388). Vaccination with two doses of the BNT162b2 vaccine led to lower production of NAbs against SARS-CoV-2 in patients with CLL/lymphomas compared with controls both on day 22 and on day 50 (p < 0.001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with Rituximab, Bruton's tyrosine kinase inhibitors, or chemotherapy was an independent prognostic factor for suboptimal antibody response. Patients with HL showed superior humoral responses to the NHL/CLL subgroups. In conclusion, patients with CLL/lymphomas have low humoral response following COVID-19 vaccination, underlining the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures. [ABSTRACT FROM AUTHOR]

The article features commentaries on the paper presented by Van Grotel and others on the treatment of pediatric nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL), with only chemotherapy without alkylating agents. While positively commenting on the work, further investigation of the results with the addition of rituximab to the standard anthracycline-based chemotherapy is recommended. NLPHL is considered an indolent disease, and less toxic treatment even in cases of multiple relapses.