Friday, August 19, 2016

Immunotherapy and pneumonitis

I am certain I dealt with pneumonitis while taking nivolumab/Opdivo for 2 1/2 years in my trial.  I noted this back in the day:

Dose 7 = 3/25/2011
   My scans at the 3 Month evaluation showed "ground glass appearance" in the right lower lobe of my lung.  I was also having wheezing at the time.  Scans were reviewed by the tumor board at Moffitt and determined to be related to my asthma or an inflammatory process that Weber had seen before in patients on ipi.  Wheezing gradually improved on albuterol and inhaled corticosteroid; symbicort. Perhaps most importantly, the 3mm something???? in my brain on my MRI when I started is GONE!

Additionally, when reviewing my records (created in this blog!!!) it was very clear that my infusions were directly followed by bouts of wheezing. It never got so bad that I had to stop my infusions or required systemic steroids, though my nurses often threatened me with them!  I dealt with my wheeze using albuterol as well as inhaled steroids (symbicort or pulmicort).  My history is a little hazy given my asthma and my work with little germy critters, but as B recently told my local onc, "Celeste, definitely experienced pneumonitis.  But, she and Weber are tough as nails, so they just powered through!"  And, as noted above, my scans were at one point read as having a "ground glass appearance"...the classic radiologic description for pneumonitis....but that's not always how pneumonitis rolls, as this latest article indicates: 

PD-1 inhibitor-related pneumonitis in advanced cancer patients: Radiographic patterns and clinical course.  Nishino, Ramaiya, Awad, ... Hodi, et al.  Clin Cancer Res. 2016 Aug 17.  

The purpose of this study was to...investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor-related pneumonitis in advanced cancer patients.  Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of pneumonitis.  Among 170 patients treated in 10 different trials of nivolumab, 20 patients (10 melanoma, 6 lymphoma, 4 lung cancer) developed pneumonitis. Five patients received nivolumab monotherapy and 15 received combination therapy. Median time from therapy initiation to pneumonitis was 2.6 months. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 13, nonspecific interstitial pneumonia (NSIP) in 3, hypersensitivity pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. AIP/ARDS pattern had the highest grade, followed by COP, while NSIP and HP had lower grade. COP pattern was most common in all tumors and treatment regimens. Most patients (17/20;85%) received corticosteroids, and 3 (15%) also required infliximab. Seven patients restarted nivolumab therapy; two of them developed recurrent pneumonitis and were successfully retreated with corticosteroids. One of the patients experienced a pneumonitis flare after completion of corticosteroid taper without nivolumab retreatment.  PD-1 inhibitor-related pneumonitis showed a spectrum of radiographic patterns, reflecting pneumonitis grades. COP was the most common pattern across tumor types and therapeutic regimens. Most patients were successfully treated with corticosteroids. Recurrent pneumonitis and pneumonitis flare were noted in a few patients.

(Found this article as it is being added as a late addition to this post...)

Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.  Nishino, Giobbie-Hurder, Hatabu, Ramaiya, Hodi.  JAMA Oncol. 2016 Aug 18.

Programmed cell death 1 (PD-1) inhibitor-related pneumonitis is a rare but clinically serious and potentially life-threatening adverse event. Little is known about its incidence across different tumor types and treatment regimens.  To compare the incidence of PD-1 inhibitor-related pneumonitis among different tumor types and therapeutic regimens.  A PubMed search through November 10, 2015, and a review of references from relevant articles. For the PubMed search, the following keywords or corresponding Medical Subject Heading terms were used: nivolumab, pembrolizumab, and PD-1 inhibitor.  Twenty-six original articles of PD-1 inhibitor trial results were identified. Among them, 20 studies of melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC) were eligible for a meta-analysis.  The data were extracted by 1 primary reviewer and then independently reviewed by 2 secondary reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comparisons of the incidence were based on marginal, exact generalized linear models with generalized estimating equations.  Incidence of all-grade and grade 3 or higher pneumonitis and pneumonitis-related deaths.  Twenty studies of single-tumor-type trials of PD-1 inhibitor (12 melanoma studies, 5 NSCLC studies, and 3 RCC studies) (a total of 4496 unique patients) were included in the meta-analysis. The overall incidence of pneumonitis during PD-1 inhibitor monotherapy was 2.7% for all-grade and 0.8% for grade 3 or higher pneumonitis. The incidence was higher in NSCLC for all-grade (4.1% vs 1.6%) and grade 3 or higher pneumonitis (1.8% vs 0.2%) compared with melanoma. The incidence in RCC was higher than in melanoma for all-grade pneumonitis (4.1% vs 1.6%) but not for grade 3 or higher pneumonitis. Four pneumonitis-related deaths were observed in patients with NSCLC in the monotherapy group. Pneumonitis was more frequent during combination therapy than monotherapy for all-grade (6.6% vs 1.6%) and grade 3 or higher pneumonitis (1.5% vs 0.2%) in melanoma, with 1 pneumonitis-related death during combination therapy. Multivariable analyses demonstrated higher odds of pneumonitis in NSCLC for all-grade and grade 3 or higher pneumonitis and in RCC for all-grade pneumonitis compared with melanoma. The combination therapy had significantly higher odds than monotherapy for all-grade and grade 3 or higher pneumonitis. The incidence of PD-1 inhibitor-related pneumonitis was higher in NSCLC and RCC and during combination therapy. These findings contribute to enhance awareness among clinicians and support further investigations to meet the clinical need.

Nothing is ever simple when dealing with melanoma, its treatments, or their side effects!!!!  If you have a wheeze or to your doc!!!  Hang in there melanoma peeps!! - c

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