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Summary: Checkpoint inhibitors (CPIs) are routinely employed in relapsed/refractory classical Hodgkin lymphoma. Nonetheless, persistent long‐term responses are uncommon, and one‐third of patients are refractory. Several reports have suggested that treatment with CPIs may re‐sensitize patients to chemotherapy, however there is no consensus on the optimal chemotherapy regimen and subsequent consolidation strategy. In this retrospective study we analysed the response to rechallenge with chemotherapy after CPI failure. Furthermore, we exploratively characterized the clonal evolution profile of a small sample of patients (n = 5) by employing the CALDER approach. Among the 28 patients included in the study, 17 (71%) were primary refractory and 26 (92%) were refractory to the last chemotherapy prior to CPIs. Following rechallenge with chemotherapy, response was recorded in 23 (82%) patients experiencing complete remission and 3 (11%) patients experiencing partial remission. The tumour evolution of the patients inferred by CALDER seemingly occurred prior to the first cycle of therapy and was characterized either by linear or branching evolution patterns. Twenty‐five patients proceeded to allogeneic stem cell transplantation. At a median follow‐up of 21 months, median PFS and OS were not reached. In conclusion, patients who fail CPIs can be effectively rescued by salvage chemotherapy and bridged to allo‐SCT/auto‐SCT. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is characterized by clinical and molecular heterogeneity; however, this heterogeneity is rarely taken into account by standard-of-care treatment approaches. While the disease was traditionally classified based on transcriptome signatures purporting the tumor cell of origin, recent classification systems have further differentiated these subtypes into clusters based on molecular and genetic features. Alongside a better understanding of the biology of the disease and the signaling pathways involved, emerging therapeutic agents may be better aimed at attacking distinct disease subsets. It is hoped that molecular subtyping at diagnosis will allow patients to be allocated to the appropriate treatment that targets their specific disease subtype, thus advancing the promise of precision medicine in lymphoma, an approach that is most needed. For high-risk disease subsets, this is particularly important, and much research is still needed to develop agents effective in this population. Here, we review recent advances in DLBCL biology and how they can be translated into clinical care. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is the second most common histotype of lymphoma and is considered an incurable disease. The need for new treatment options has led to the development of innovative targeted agents, including inhibitors of the phosphatidylinositol-3-kinase (PI3K) pathway. Copanlisib, an intravenous pan–class I PI3K inhibitor, has been approved by the US Food and Drug Administration (FDA) for the treatment of relapsed FL in patients who have received at least two prior systemic therapies. In this article, we critically review the mechanism of action, clinical efficacy, safety, dosage, administration, and role of copanlisib in the treatment of relapsed FL. Treatment with copanlisib results in clinically relevant and durable responses in heavily pretreated patients with relapsed or refractory FL. In addition, copanlisib has a manageable safety profile in this population, with low rates of severe hepatic transaminitis, diarrhea, colitis, and noninfectious pneumonitis. Further investigations of copanlisib within combination regimens will potentially allow to move copanlisib to an earlier line of therapy for FL. However, results of the CHRONOS-4 clinical trial evaluating copanlisib with standard chemoimmunotherapy (rituximab with bendamustine or CHOP) are not yet available. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is a heterogeneous disease with varying prognosis owing to differences in clinical, laboratory, and disease parameters. Although generally considered incurable, prognosis for early‐ and advanced‐stage disease has improved because of therapeutic advances, several of which have resulted from elucidation of the biologic and molecular basis of the disease. The choice of treatment for FL is highly dependent on patient and disease characteristics. Several tools are available for risk stratification, although limitations in their routine clinical use exist. For limited disease, treatment options include radiotherapy, rituximab monotherapy or combination regimens, and surveillance. Treatment of advanced disease is often determined by tumor burden, with surveillance or rituximab considered for low tumor burden and chemoimmunotherapy for high tumor burden disease. Treatment for relapsed or refractory disease is influenced by initial first‐line therapy and the duration and quality of the response. Presently, there is no consensus for treatment of patients with early or multiply relapsed disease; however, numerous agents, combination regimens, and transplant options have demonstrated efficacy. Although the number of therapies available to treat FL has increased together with an improved understanding of the underlying biologic basis of disease, the best approach to select the most appropriate treatment strategy for an individual patient at a particular time continues to be elucidated. This review considers prognostication and the evolving treatment landscape of FL, including recent and emergent therapies as well as remaining unmet needs. Implications for Practice: In follicular lymphoma, a personalized approach to management based on disease biology, patient characteristics, and other factors continues to emerge. However, application of current management requires an understanding of the available therapeutic options for first‐line treatment and knowledge of current development in therapies for previously untreated and for relapsed or refractory disease. Thus, this work reviews for clinicians the contemporary data in follicular lymphoma, from advances in characterizing disease biology to current treatments and emerging novel therapies. Therapeutic advances have improved prognosis for follicular lymphoma, although the disease is still incurable. This comprehensive clinical review considers prognostic approaches and the treatment landscape for follicular lymphoma, including emerging therapies and unmet needs. [ABSTRACT FROM AUTHOR]

Chemotherapy is associated with toxicity in elderly patients with potentially curable malignancies, posing the dilemma of whether to intensify therapy, thereby improving the cure rate, or deescalate therapy, thereby reducing toxicity, with consequent risks for under- or overtreatment. Adequate tools to define doses and combinations have not been identified for lymphoma patients. We conducted a prospective trial aimed to evaluate the feasibility and efficacy of chemotherapy modulated according to a modified comprehensive geriatric assessment (CGA) in elderly (aged ≥70 years) patients with diffuse large B-cell lymphoma (DLBCL). In June 2000 to March 2006, 100 patients were stratified using a CGA into three groups (fit, unfit, and frail), and they received a rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone modulated in dose and drugs according to comorbidities and activities of daily living (ADL) and instrumental ADL scores. Treatment was associated with a complete response rate of 81% and mild toxicity: grade 4 neutropenia in 14%, anemia in 1%, and neurological and cardiac toxicity in 2% of patients. At a median follow-up of 64 months, 51 patients were alive, with 5-year disease-free, overall, and causespecific survival rates of 80%, 60%, and 74%, respectively. Chemoimmunotherapy adjustments based on a CGA are associated with manageable toxicity and excellent outcomes in elderly patients with DLBCL. Wide use of this CGA-driven treatment may result in better cure rates, especially in fit and unfit patients. [ABSTRACT FROM AUTHOR]

Abstract: Many progresses have been made in the management of non-Hodgkin''s lymphoma and Hodgkin''s lymphoma. Newer chemotherapeutic regimens, extended use of PET to evaluate the stage and mainly the response after treatment, rituximab and other monoclonal antibodies, radioimmunoconjugates, and allogeneic stem cell transplantation, all contribute to a better treatment of these diseases. Furthermore, risk-adapted treatment can reduce late toxicities, such as cardiovascular disease, secondary myelodysplastic syndrome, and solid tumors. [Copyright &y& Elsevier]

Our goal was to optimize use of granulocyte colony-stimulating factor (G-CSF) after high-dose chemotherapy and autologous peripheral blood stem-cell transplantation in lymphoma patients, limiting G-CSF administration to patients infusing a suboptimal CD34+ cell number. Of 124 consecutive patients with histologically proven Hodgkin's and non-Hodgkin's lymphoma from January 2001 to June 2004, 60 patients (group 1) given ≥5 × 106/kg CD34+ cells received no G-CSF; 64 patients (group 2) given ≤5 × 106/kg CD34+ cells received G-CSF from day +5 after stem-cell reinfusion. The median times to reach 0.5 × 109/L and 1.0 × 109/L neutrophils were, respectively, 3 and 4 d shorter in G-CSF group and this difference was statistically significant ( P = 0.0014; P = 0.0001). In terms of antibiotic and antimycotic requirements, gastrointestinal toxicity, days of hospitalization, and transfusion requirements, no differences were demonstrated between the two groups. No statistically significant difference was demonstrated for the total number of febrile episodes (52 for group 1; 53 for group 2; P = 0.623) and the median number of febrile days (2 d for both groups). Myeloid reconstitution values for both groups agree with published results for autotransplanted patients treated with G-CSF from 7 to 14 d. Also, major clinical events, antibiotic, antimycotic, and transfusion requirements, and hospital stay were similar to published findings. Our data suggest that G-CSF administration can be safely optimized, used only for patients infused with a suboptimal CD34+ cell dose. [ABSTRACT FROM AUTHOR]

Abstract: The majority of patients with early-stage (IA–IIA) Hodgkin''s disease (HD) can at present be cured by current available therapeutic options. Actually the “gold standard” for patients with early-stage HD is a combined approach consisting of a short-duration chemotherapy (e.g., two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; ABVD) and low-dose (20–30Gy) involved-field irradiation (IF-RT). The treatment of choice for advanced-stage HD is still represented by chemotherapy alone or followed by RT. At present, it is internationally accepted that ABVD should be the standard regimen. High-dose chemotherapy (HDC) with peripheral-blood stem-cell support (PBSCs) represents the treatment of choice for patients relapsing after chemotherapy, but, nevertheless, about 50% of transplanted patients relapse or progress after HDC. Regarding low- and high-grade non-Hodgkin''s lymphomas, Rituximab associated or not to chemotherapy, is much more extensively used. In advanced low-grade lymphomas the role of immunochemotherapy has been definitively demonstrated in a phase III study, comparing eight courses of rituximab plus chemotherapy (CVP regimen) versus CVP alone at diagnosis. Three courses of CHOP plus Rituximab associated to involved fields radiotherapy (RT) is considered to be the standard treatment in localized high-grade lymphoma. In advanced disease patients, intensified CHOP-like regimen and new therapeutic agents have been tried to improve the clinical results in newly diagnosed patients with encouraging results. Finally, several studies confirmed the usefulness of prognostic scores as IPI for high-grade lymphoma and FLIPI for follicular lymphoma, and the usefulness of PET in the staging of lymphomas. [Copyright &y& Elsevier]

Objective: There is little information on Herpes zoster infection in breast cancer patients as a complication during adjuvant chemotherapy. The aim of this study is to evaluate the incidence of Herpes zoster and simplex infections in this patients setting. Methods: We analyzed 623 early-stage breast cancer patients in our Institute over a period of 7 years (1998–2005). Four-hundred and sixty-onepatients were treated with anthracycline-based chemotherapy, 116 with CMF and 46 with taxane-containing regimens. Results: Twelve (1.9%) developed herpes zoster; 9 patients, receiving anthracycline-based chemotherapy, two taxane-containing regimens, and one CMF regimen. Herpes zoster infection required treatment delay in 6 patients. Adjuvant chemotherapy was delayed for 1 week in 2 patients, while in 4 patients with more severe symptoms chemotherapy was delayed for 2 weeks. One patient, despite i.v. acyclovir, had severe postherpetic motor neuropathy with a permanent ambulation impairment, and chemotherapy was stopped. In our study, herpes zoster occurred in 55/1,000 cases/year. The reported incidence in the general population varies between 2.2 and 4.1 per 1,000 patients/year; therefore, the risk of developing herpes zoster in these patients may be 13- to 25-fold higher compared to the incidence in the general population. In addition, 13 of 623 patients developed herpes simplex. Conclusion: Our findings suggest that adjuvant chemotherapy can facilitate reactivation of herpes infection. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the chemotherapy of patients with early-stage Hogkin lymphoma.

Discusses the medical condition called autoimmunity. Definition of autoimmunity; Cases of splenic marginal zone cell lymphoma discovered after splenectomy in patients treated for refractory idiopathic thrombocytopenic purpura.