Patterns of progression after immune checkpoint inhibitors for Hodgkin lymphoma: implications for radiation therapy.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have demonstrated remarkable response rates in relapsed or refractory Hodgkin lymphoma (HL). Still, most patients eventually progress. Patterns of progression after ICIs are not well described and are essential to defining the role of local therapies in combination with ICIs. We identified patients who received ICIs for HL between 2013 and 2022. Fludeoxyglucose-18 positron emission tomography (FDG-PET) before initiating ICI and at progression on/after ICI were reviewed, and areas of active HL were recorded. An exploratory analysis of treatable progression included patients with ≤5 sites of disease on pre-ICI FDG-PET and progression only at pre-ICI sites. Ninety patients were identified; 69 had complete records, and of these, 32 (52%) had relapsed at ICI initiation, 17 (25%) were refractory, and 16 (23%) received ICI as first-line therapy. Forty-five of 69 patients had ≤5 sites of disease (limited) on pre-ICI FDG-PET. Patients with >5 sites of disease had a higher risk of progression, and every site of disease >5 sites conferred an additional 1.2x higher chance of progression. At a median follow-up of 4.0 years, 41 of 69 patients had progressed on/after ICIs (cumulative incidence 66.4%), and of these, 22 of 41 patients progressed only at pre-ICI sites (cumulative incidence 39.4%). In an exploratory analysis, the cumulative incidence of a treatable progression among 45 patients with limited disease was 34%. The cumulative incidence of any progression among this cohort was 58.9%. More than one-third of patients with limited disease before ICIs experienced progression only at pre-ICI sites of disease. These patients could be candidates for radiation during or after ICIs.

The impact of dose modification and temporary interruption of ibrutinib on outcomes of chronic lymphocytic leukemia patients in routine clinical practice.

To study the impact of dose modification and temporary interruption of ibrutinib in routine clinical practice, we conducted a retrospective study of consecutive CLL patients treated with ibrutinib outside the context of a clinical trial at Mayo Clinic, (Rochester, MN) from 11/2013 to 12/2017. Of 209 patients, 131 (74%) had unmutated IGHV, 38 (20%) had TP53 disruption, and 47 (22%) were previously untreated. A total of 87/209 (42%) patients started reduced dose ibrutinib (<420 mg daily; n = 43, physician preference; n = 33, concomitant medications; and n = 11, other). During 281 person-years of treatment, 91/209 patients had temporary dose interruption (54%, nonhematologic toxicity; 29%, surgical procedures; 10%, hematologic toxicity; and 7%, other). After a median follow-up of 24 months, the estimated median event-free survival (EFS) was 36 months, and median overall survival (OS) was not reached. On multivariable analyses, temporary ibrutinib interruption (hazard ratio [HR]: 2.37, P = .006) and TP53 disruption at ibrutinib initiation (HR: 1.81, P = .048) were associated with shorter EFS, whereas only TP53 disruption (HR: 2.38, P = .015) was associated with shorter OS. Initial ibrutinib dose and dose modification during therapy did not appear to impact EFS or OS. These findings illustrate the challenges associated with continuous oral therapy with ibrutinib in patients with CLL.

Effect of Linezolid on Hematologic Recovery in Newly Diagnosed Acute Myeloid Leukemia Patients Following Induction Chemotherapy.

OBJECTIVE: Assess the effects of linezolid on hematologic outcomes in newly diagnosed patients with acute myeloid leukemia (AML) following induction chemotherapy. DESIGN: Single-center, retrospective, observational, cohort study. SETTING: Large, tertiary care academic medical center. PATIENTS: A total of 225 patients ≥ 18 years admitted between December 2010 and 2013 with newly diagnosed AML were assessed for inclusion. Patients were identified through the use of ICD-9 codes and chemotherapy ordered via the computerized physician order entry system. Sixty-eight patients met inclusion criteria and were grouped into two arms based on antimicrobial treatment: LZD group (linezolid plus gram-negative antimicrobial, n=21) or control group (vancomycin or daptomycin plus gram-negative antimicrobial, n=47). INTERVENTIONS: The LZD group received linezolid ≥ 72 hours. The control group received vancomycin or daptomycin ≥ 72 hours. If patients switched extended gram-positive therapy, they were included in the LZD group as long as they had received ≥ 72 hours of linezolid. MEASUREMENTS/RESULTS: The primary end point of time to neutrophil recovery was not statistically different (28 days for LZD group vs 26 days for control group; p=0.675). The preplanned subgroup analysis of patients who received ≥ 14 days of linezolid demonstrated statistically similar median times to neutrophil recovery (29 days for LZD group vs 26 days for control group; p=0.487). Total duration of extended gram-positive antimicrobial therapy was significantly longer in the LZD group (27 days vs 16 days; p<0.001). Secondary end points not found to be statistically significant included platelet count at time of neutrophil recovery, duration of neutropenia, and length of hospital stay. CONCLUSIONS: There were no significant differences in hematologic outcomes in newly diagnosed AML patients who received linezolid for extended gram-positive antimicrobial coverage following induction chemotherapy. This study provides new insight with a primary focus on the effects of hematologic outcomes when using linezolid in a well-defined acute leukemia population. Further study is warranted with larger populations to assess the potential adverse effects linezolid may have in patients with acute leukemia.