Novel Therapies for Aggressive B-Cell Lymphoma

Aggressive B-cell lymphoma (BCL) comprises a heterogeneous group of malignancies, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and mantle cell lymphoma (MCL). DLBCL, with its 3 subtypes, is the most common type of lymphoma. Advances in chemoimmunotherapy have substantially improved disease control. However, depending on the subtype, patients with DLBCL still exhibit substantially different survival rates. In MCL, a mature B-cell lymphoma, the addition of rituximab to conventional chemotherapy regimens has increased response rates, but not survival. Burkitt lymphoma, the most aggressive BCL, is characterized by a high proliferative index and requires more intensive chemotherapy regimens than DLBCL. Hence, there is a need for more effective therapies for all three diseases. Increased understanding of the molecular features of aggressive BCL has led to the development of a range of novel therapies, many of which target the tumor in a tailored manner and are summarized in this paper

Real‐world clinical effectiveness and safety of CT‐P10 in patients with diffuse large B‐cell lymphoma: An observational study in Europe

The rituximab biosimilar CT‐P10 is approved for the treatment of non‐Hodgkin lymphoma. Previous studies have demonstrated clinical similarity between CT‐P10 and reference rituximab. However, real‐world data relating to treatment in patients with DLBCL with rituximab biosimilars are limited. This study collected real‐world data relating to the effectiveness and safety of CT‐P10 treatment from the medical records of 389 patients with DLBCL (24 centers, five European countries). For the primary outcome (clinical effectiveness), overall survival (OS), progression‐free survival (PFS), and best response (BR) were assessed. The percentage (95% confidence interval [95% CI]) of patients alive at 12‐, 18‐, and 30 months postindex (initiation of CT‐P10) was 86% (82.4%–89.4%), 81% (76.9%–84.9%), and 76% (71.2%–80.1%), respectively. The PFS rate (percent, [95% CI]) at 12‐, 18‐, and 30 months postindex was 78% (74.2%–82.5%), 72% (67.9%–76.9%), and 67% (61.9%–71.7%), respectively. Median OS/PFS was not reached. For 82% (n = 312) of patients, the BR to CT‐P10 was a complete response. Adverse events were consistent with known effects of chemotherapy. This international, multicenter study provides real‐world data on the safety and effectiveness profile of CT‐P10 for DLBCL treatment and supports the adoption of CT‐P10 for the treatment of DLBCL

Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma

Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma

The PI3Kδ inhibitor zandelisib on intermittent dosing in relapsed/refractory follicular lymphoma: Results from a global phase 2 study

In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune‐related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2–8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9–80.4), the complete response (CR) rate was 38% (95% CI, 29.3–47.3), and the median DOR was 16.4 months (95% CI, 9.5–not reached). With a median follow‐up of 14.3 months (range, 1–30.5), the median progression‐free survival was 11.6 months (95% CI, 8.3–not reached). Twenty‐one patients (17%) discontinued therapy due to an adverse event. Grade 3–4 class‐related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non‐infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class‐related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B‐cell malignancies

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

ABSTRACT Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach

Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia

Background: chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. Methods: we randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. Results: the median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. Conclusions: ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.)

Radioimmunotherapy as the first line of treatment in non-Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy. The estimated deaths and new cases of NHL in the USA in 2018 have reached 19,910 and 74,680, respectively, with 5-year survival rate of 71%. Therapeutic interventions for NHL consist of chemotherapy, radiation therapy and immunotherapy. Radioimmunotherapy (RIT) is a potential alternative treatment for NHL that is currently used in different lines of treatment. Studies show that nuclear medicine physicians and radiation oncologists are not yet certain about the proper line for administration of RIT. Herein, we have reviewed the efficiency and toxicity of RIT as the first line of treatment, and discussed potential novel indications, and strategies such as modifying induction therapy and using rituximab maintenance to optimize the efficiency of RIT as the first line of treatment. Our review indicates that it is more logical to postpone conventional therapies to the second or third lines of treatment instead of RIT