Publications

BACKGROUND

Targeted therapies and checkpoint blockade therapy (CBT) have shown efficacy for patients with Hodgkin lymphoma (HL) in the relapsed and refractory (R/R) setting, but once discontinued owing to progression or side effects, it is unclear how successful further therapies will be. Moreover, there are no data on optimal sequencing of these treatments with standard therapies and other novel agents. In a multicenter, retrospective analysis, we investigated whether exposure to CBT could sensitize HL to subsequent therapy.

MATERIALS AND METHODS

Seventeen centers across the U.S. and Canada retrospectively queried medical records for eligible patients. The primary aim was to evaluate the overall response rate (ORR) to post-CBT treatment using the Lugano criteria. Secondary aims included progression-free survival (PFS), duration of response, and overall survival (OS).

RESULTS

Eighty-one patients were included. Seventy-two percent had stage III-IV disease, and the population was heavily pretreated with a median of four therapies before CBT. Most patients (65%) discontinued CBT owing to progression. The ORR to post-CBT therapy was 62%, with a median PFS of 6.3 months and median OS of 21 months. Post-CBT treatment regimens consisted of chemotherapy (44%), targeted agents (19%), immunotherapy (15%), transplant conditioning (14%), chemotherapy/targeted combination (7%), and clinical trials (1%). No significant difference in OS was found when stratified by post-CBT regimen.

CONCLUSION

In a heavily pretreated R/R HL population, CBT may sensitize patients to subsequent treatment, even after progression on CBT. Post-CBT regimen category did not impact OS. This may be a novel treatment strategy, which warrants further investigation in prospective clinical trials.

IMPLICATIONS FOR PRACTICE

Novel, life-prolonging treatment strategies in relapsed and refractory (R/R) Hodgkin lymphoma (HL) are greatly desired. The results of this multicenter analysis concur with a smaller, earlier report that checkpoint blockade therapy (CBT) use in R/R HL may sensitize patients to their subsequent treatment. This approach may potentially enhance therapeutic options or to bridge patients to transplant. Prospective data are warranted prior to practice implementation. As more work is done in this area, we may also be able to optimize sequencing of CBT and novel agents in the treatment paradigm to minimize treatment-related toxicity and thus improve patient quality of life.

OBJECTIVES

To develop a prognostic model for hospital admissions over a 1-year period among community-dwelling older adults with self-reported hearing and/or vision impairments based on readily obtainable clinical predictors.

DESIGN

Retrospective cohort study.

SETTING

Medicare Current Beneficiary Survey from 1999 to 2006.

PARTICIPANTS

Community-dwelling Medicare beneficiaries, aged 65 years and older, with self-reported hearing and/or vision impairment (N = 15,999).

MEASUREMENTS

The primary outcome was any hospital admission over a predefined 1-year study period. Candidate predictors included demographic factors, prior healthcare utilization, comorbidities, functional impairment, and patient-level factors. We analyzed the association of all candidate predictors with any hospital admission over the 1-year study period using multivariable logistic regression. The final model was created using a penalized regression method known as the least absolute shrinkage and selection operator. Model performance was assessed by discrimination (concordance statistic (c-statistic)) and calibration (evaluated graphically). Internal validation was performed via bootstrapping, and results were adjusted for overoptimism.

RESULTS

Of the 15,999 participants, the mean age was 78 years and 55% were female. A total of 2,567 participants (16.0%) had at least one hospital admission in the 1-year study period. The final model included seven variables independently associated with hospitalization: number of inpatient admissions in the previous year, number of emergency department visits in the previous year, activities of daily living difficulty score, poor self-rated health, and self-reported history of myocardial infarction, stroke, and nonskin cancer. The c-statistic of the final model was 0.717. The optimism-corrected c-statistic after bootstrap internal validation was 0.716. A calibration plot suggested that the model tended to overestimate risk among patients at the highest risk for hospitalization.

CONCLUSION

This prognostic model can help identify which community-dwelling older adults with sensory impairments are at highest risk for hospitalization and may inform allocation of healthcare resources.