PIMs and NHL Outcomes

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This study was developed so that researchers might better understand why elderly patients with aggressive NHL have worse outcomes. Dr Diefenbach said that “it’s important to identify and tease out geriatric-related issues that are potentially correctable to improve the outcomes of patients and to increase the number of elderly patients who could possibly be treated with high-dose curative intent therapy.”

“This study was a first step to identify geriatric problems,” Dr Diefenbach said.

In the study, 171 patients age 60 or older with NHL diagnosed between 2009 and 2014 at 2 different hospitals were followed for a median of 28 months.1 NHL outcomes were evaluated according to PIM use, number of medications, International Prognostic Index (IPI), Charlson Comorbidity Index (CCI), demographics, and laboratory parameters. PIM use was classified according to the 2015 Beers criteria.

At baseline, the median age of the cohort was 70 (interquartile range [IQR], 65-77) and NHL subtypes included diffuse large B cell, aggressive T cell, blastic mantle cell, and other aggressive lymphomas. The median number of medications at diagnosis was 4 (IQR, 2-7) and at least 1 PIM was used by 47% of patients, with the most common PIMs including metoclopramide, proton-pump inhibitors, benzodiazepines, and tricyclics.

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All patients received curative-intent treatment, which was primarily cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab (R-CHOP). Treatment delays occurred among 59% of patients; 65% of patients experienced grade 3 or 4 higher treatment-related adverse events (AEs). Occurrence of a treatment delay or dose reduction was significantly associated with albumin level and IPI.

There was an insignificant trend toward an association between PIM use and treatment delay or dose reduction (P = .053).

PIM use was significantly associated with prolonged progression-free survival (PFS; P < .001) and overall survival (P = .008) and remained a strong independent predictor of PFS (hazard ratio [HR], 2.81; 95% CI, 1.36-5.81; P = .005) and OS (HR, 3.12; 95% CI, 1.49-6.52; P = .003) after multivariate analysis.


The mechanisms underlying the association between PIM use and worse NHL outcomes are, however, not clear. The investigators postulated that PIM use may indicate underlying comorbidities, which may affect NHL outcomes, though multivariate analysis accounted for comorbidities by using the CCI.

PIMs may also cause drug-drug interactions, which can lead to treatment-related toxicities and consequently affect outcomes.

“Alternatively, or additionally, PIMs may worsen other geriatric symptoms, leading to functional decline and other morbidities,” Dr Diefenbach said.


Though the study demonstrated an independent association between PIM use and NHL outcomes, it does not prove causality. Dr Diefenbach noted that a prospective trial is needed to further evaluate the role of PIMs on NHL outcomes.

As a result of these findings, Dr Diefenbach recommends that “before initiating intensive chemotherapy for an elderly frail NHL patient, the oncologist should review the medication list carefully, identify the potential PIMs, and either consider stopping them for the duration of therapy, or, if that is not feasible, consult with a pharmacist or geriatrician.”

She noted that “this can be done in the clinic setting without too much difficulty or additional expense, and may significantly improve the outcomes of elderly frail patients.”


  1. Lin RJ, Ma H, Guo R, Troxel AB, Diefenbach CS. Potentially inappropriate medication use in elderly non-Hodgkin lymphoma patients is associated with reduced survival and increased toxicities. Br J Haematol. 2017 Nov 16. doi: 10.1111/bjh.15027 [Epub ahead of print]
  2. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63:2227-46. doi: 10.1111/jgs.13702