ABSTRACT
Chronic lymphocytic leukemia (cll) is the most common adult leukemia in the Western world. Unfortunately, affected patients are often immunosuppressed and at increased risk of infection and secondary malignancy. Previous meta-analysis has found that patients with cll have a risk of melanoma that is increased by a factor of 4 compared with the general population. Recent advances in the understanding of the PD receptor pathway have led to immunotherapies that target cancer cells. The use of PD-1 inhibitors is now considered first-line treatment for BRAF wild-type metastatic melanoma. Interestingly, early preclinical data suggest that inhibition of that pathway could also be used in the treatment of cll; however, recent clinical data did not support the effectiveness of that approach. In this case series, we highlight 2 cases in which patients with cll and concurrent malignant melanoma underwent treatment with PD-1 inhibitors and were found to experience reductions in their white blood cell counts without improvement in their hemoglobin. Those cases further illustrate that treatment of cll with PD-1 inhibitors is ineffective.
Subject(s)
Immunotherapy/methods , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Melanoma/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Aged, 80 and over , Female , HumansABSTRACT
Background: Ibrutinib is an approved treatment for relapsed or refractory chronic lymphocytic leukemia (cll) and small lymphocytic lymphoma (sll). The effect of ibrutinib dose reduction compared with discontinuation in a population-based setting is unclear. Methods: To examine the patterns of ibrutinib use in a Canadian population-based setting, we analyzed a retrospective cohort of patients with relapsed or refractory cll or sll treated with ibrutinib. Results: The 64 patients diagnosed with cll or sll had a median age of 76.5 years. Most had unmutated ighv (immunoglobulin variable heavy chain). A hematologic response occurred in 39 patients regardless of the ibrutinib dose. The most common toxicities were infection, bruising or bleeding, and musculoskeletal problems, with a median time to first toxicity of 14 days. More than half the cohort experienced a dose reduction, with musculoskeletal problems, cytopenias, and infection being the leading causes; surgery was the most frequent indication for holding treatment. Only 26 of the 64 patients (40.6%) stayed on the recommended maximal dose of ibrutinib. No differences in reported toxicities or hematologic response rates were evident between the patients receiving maximal and submaximal therapy. At the end of the study period, 53 patients from the initial cohort remained on ibrutinib. Conclusions: More than half the study patients received ibrutinib therapy at a submaximal dose without evidence of increased frequency of toxicities or disease progression. The rate of ibrutinib discontinuation was lower in our cohort than has been reported in other settings. Submaximal ibrutinib dosing will have to be further systematically evaluated.
Subject(s)
Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Antineoplastic Agents/administration & dosage , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Protein Kinase Inhibitors/administration & dosage , Pyrazoles/administration & dosage , Pyrimidines/administration & dosage , Adenine/analogs & derivatives , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Canada , Female , Humans , Male , Middle Aged , Piperidines , Protein Kinase Inhibitors/adverse effects , Pyrazoles/adverse effects , Pyrimidines/adverse effects , Treatment OutcomeABSTRACT
The latest generation gamma-ray detection system, GAMMASPHERE, coupled with the Microball charged-particle detector, has made possible a new class of nuclear lifetime measurement. For the first time differential lifetime measurements free from common systematic errors for over 15 different nuclei ( >30 rotational bands in various isotopes of Ce, Pr, Nd, Pm, and Sm) have been extracted at high spin within a single experiment. This comprehensive study establishes the effective single-particle transition quadrupole moments in the A approximately 135 light rare-earth region. Detailed comparisons are made with theoretical calculations using the self-consistent cranked mean-field theory which convincingly demonstrates the validity of the additivity of single-particle quadrupole moments in this mass region.
