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Indolent lymphomas: pushing the pace with novel agents.

ABSTRACT: Chemoimmunotherapy has been a hallmark of treatment of indolent B-cell non-Hodgkin lymphomas for the past 2 decades, with high response rates seen but relapses nearly inevitable and patients spending, on average, 20 years on and off treatment. Treatment advances, then, should be aimed at maintaining efficacy while minimizing toxicity or at achieving cure. Improved understanding of the genetic and molecular features of these diseases, as well as of the interaction between the tumor cell and its immune microenvironment, has resulted in an accelerated expansion of tolerable treatment options for patients, with new combinations of therapy holding promise that definitive therapy in these diseases is possible. These drugs include immunomodulating agents such as lenalidomide, small-molecule inhibitors of the B-cell receptor signaling pathway such as ibrutinib and idelalisib, B-cell lymphoma 2 homology 3 mimetics such as venetoclax, and enhancer of zeste homolog 2 inhibitors such as tazemetostat. Therapies that improve the host immune response against the malignant B cell are also of great interest, given the durable remission seen after allogeneic stem cell transplant in these diseases, and immune checkpoint inhibitors, agonist antibodies against immunostimulatory T-cell receptors, antibody-drug conjugates, bispecific antibodies, and finally chimeric antigen receptor T cells are all being investigated, with promising early efficacy signals. These treatments may not necessarily replace chemotherapy but rather augment it in an attempt to improve quality of life and survival for these patients.

SUBMITTER: Jacobson CA

PROVIDER: S-EPMC6913469 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Indolent lymphomas: pushing the pace with novel agents.

Jacobson Caron A CA

Hematology. American Society of Hematology. Education Program 20191201 1

Chemoimmunotherapy has been a hallmark of treatment of indolent B-cell non-Hodgkin lymphomas for the past 2 decades, with high response rates seen but relapses nearly inevitable and patients spending, on average, 20 years on and off treatment. Treatment advances, then, should be aimed at maintaining efficacy while minimizing toxicity or at achieving cure. Improved understanding of the genetic and molecular features of these diseases, as well as of the interaction between the tumor cell and its i ...[more]

PMID: 31808854

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Project description:BackgroundPatients with indolent B-cell non-Hodgkin lymphomas (B-NHLs) have an increased risk of infections which is caused by pathomechanisms of the diseases itself but also as a result of anti-tumor therapy. Especially the effects of anti-CD20 antibodies are well understood as these lead to decreased antibody production. Most studies regarding immunodeficiency in B-NHLs were conducted with multiple myeloma and chronic lymphocytic leukemia patients. As these studies not always represent the general population we collected and analyzed real world data from patients with indolent lymphomas and a control group (CG).ResultsPatients with B-NHLs undergoing therapy or who were regularly monitored in a watch and wait approach had, over the time of one year, an increased rate of infections compared to the CG of 145 healthy volunteers (mean: 11.66 vs. 7.13 infections per 1000 days). Consistent with this finding B-NHL patients received more antibiotic treatment (mean: 11.17 vs. 6.27 days) and were more often hospitalized than persons from the CG (mean: 5.19 vs. 0.99 days per 1000 days). Lymphoma patients without immunodeficiency had a lower infection rate than patients with non-symptomatic and symptomatic immunodeficiency (mean: 10.91 vs. 12.07 and 12.36 per 1000 days). The number of infections differed statistically significant for the subgroups and CG (7.13 per 1000 days). Patients with symptomatic immunodeficiency were mostly treated with regular immunoglobulin substitutions and infection rates were comparable to those of patients with asymptomatic immunodeficiency.ConclusionsOur data suggest the use of an approach with regular immune monitoring including the measurement of immunoglobulin levels and regular appointments for clinical assessment of all indolent lymphoma patients in order to identify patients with increased risk of infections. It also raises the question if patients with immunodeficiency should be treated more often with regular immunoglobulin substitution, but so far more studies are necessary to answer this question.

Project description:PurposeRadiation therapy (RT) with doses ranging from 24 Gray (Gy) to 40 Gy is a proven treatment modality for indolent orbital adnexal lymphoma (IOAL), but recently the use of low dose RT (LDRT, defined as 2 Gy x 2 fractions) has become a notable alternative. However, limited data exists comparing outcomes following LDRT to moderate-dose RT (MDRT, RT dose 4 - 36 Gy). We present a single institution retrospective analysis comparing outcomes of patients with IOALs following LDRT or MDRT.MethodsA total of 36 patients treated with 38 consecutive courses of RT were identified; LDRT was delivered for 14 courses and MDRT for 24 courses. Overall response rates (ORR) were recorded according to Deauville or RECIST criteria with a response characterized as a complete response (CR) or partial response. Local control (LC), orbital control (OC), and overall survival (OS) rates were estimated with the Kaplan-Meier method. RT toxicity was graded per CTCAEv5 and compared with the Fisher's exact test.ResultsMedian follow-up time was 29 months (m) (range, 4-129m), and median MDRT dose used was 24 Gy (range 21-36 Gy). Overall response rates (ORR) were 100% (CR 50%) and 87.5% (CR 58.3%) following LDRT and MDRT, respectively. OS at 2 years was 100% and 95% for the LDRT and MDRT groups, respectively (p=0.36). LC rates at 2 years was 100% for both LDRT and MDRT groups and at 4 years was 100% and 89% for the LDRT and MDRT groups, respectively (p=0.56). The 4-year OC rate (including both ipsilateral and contralateral relapses) was 80% and 85% for the LDRT and MDRT groups, respectively (p=0.79). No patient required treatment with RT to a previously irradiated orbit. Acute toxicities were reported following 6 LDRT courses compared to 20 MDRT courses (p=.014). No Grade 3 or higher acute toxicities occurred in either group. Late toxicities were reported following 2 LDRT courses compared to 10 MDRT courses (p=0.147).ConclusionsLDRT produced similar ORR, LC, OC, and OS rates compared to MDRT with fewer acute and minimal late toxicities reported. Future multi-center studies with larger patient numbers are warranted to show significant associations.

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Indolent lymphomas: pushing the pace with novel agents.

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Indolent lymphomas: pushing the pace with novel agents.

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