Nurse-Developed Algorithm Helps Identify Pneumocystis Pneumonia Risk

An algorithm developed by nurses at Huntsman Cancer Institute may be effective in monitoring and initiating treatment for pneumocystis jirovecii pneumonia (PJP) risk in patients with multiple myeloma receiving novel, high-risk therapies, according to Carrie Bellerive, BSN, RN, BMTCN.

“As a result of our nursing intervention, nursing practice has been elevated to allow for quick identification of patients [who are] at high risk for PJP and intervene for each patient as needed,” Bellerive, who is an outpatient clinical nurse specialist with the Multiple Myeloma Nursing Team and Bone Marrow Transplant Clinic with the Huntsman Cancer Institute at the University of Utah, said during a presentation on the algorithm as part of the International Myeloma Society’s 6th Annual Nursing Symposium.

The continued approval of novel therapies, such as chimeric antigen receptor (CAR) T-cell therapy and T-cell redirecting bispecific antibodies, are revolutionizing myeloma treatment, she explained. However, opportunistic infection risk increases with these treatments because of immunosuppression.

PJP is an opportunistic organism which can induce life-threatening pneumonia. Moreover, patients undergoing therapies often experience decreased CD4 T-cell count. This decrease compounds risk for PJP. Other risk factors included solid tumor transplants, HIV, autoimmune diseases, and anti-TNF therapy, some biological therapies and chemotherapy, and long-term corticosteroid use.

“This infection presents substantial morbidity and occasional mortality to our patient population,” Bellerive said. “Even when patients recover, it can cause prolonged treatment interruptions.”

According to Bellerive, the approach that nurses at Huntsman use to prophylaxis patients against PJP is as follows:

• Patients who receive a diagnosis of PJP are prescribed lifetime prophylaxis while on treatment
• For patients receiving CAR T-cell therapy, allogeneic, or autologous stem cell transplant (alloSCT; ASCT)
  • Prophylaxis for 6 months
  • Monitor CD4 values for 2 consecutive values, 1 month apart, until they are greater than 200/mm³
    • If CD4 values stay above 200/mm³, discontinue prophylaxis after 180 days; continue to check CD4 values
    • Continue checking CD4 counts, every 3 months, indefinitely
    • If one of those values falls below 200/mm³, reinitiate prophylaxis
• For patients who have completed the high-risk treatments mentioned above
  • Consider reinitiation of prophylaxis and/or monitoring when the patient begins a daratumumab based regimen
    • Monitor CD4 until 3 consecutive months are greater than 200/mm³; patients remain off prophylaxis unless a value drops below 200/mm³

In terms of prophylaxis, trimethoprim-sulfamethoxazole represents is the recommended first choice, followed by monthly pentamidine, dapsone, and atovaquone, if a patient is allergic or ineligible for one of the prior recommended therapies. Patients receiving dapsone must be assessed for potential glucose-6-phosphate dehydrogenase deficiency.

According to Bellerive, evidence suggests that CD4 T-cell count monitoring is useful in anticipating PJP development, but data is suboptimal across hematologic malignancies. Most of the published literature on PJP development is focused on solid tumors, transplant, HIV, or autoimmune conditions, such as irritable bowel syndrome and rheumatoid arthritis.

Moreover, the current National Comprehensive Cancer Network guidelines, which advise providers to prophylaxis patients with multiple myeloma who receive either alloSCT or immunosuppressive therapies for 6 months, and to prophylaxis those receiving ASCT for 3 to 6 months, have yet to incorporate more novel therapies, such as ciltacabatagene autoleucel (Carvykti).^2,3

To that end, nurse investigators based out of the Huntsman Cancer Institute sought to standardize the approach to PJP prophylaxis for patients in the multiple myeloma units.

“We know that when standardized prophylaxis is used during key points in the patient treatment lifecycle, the risk for PJP is reduced,” Bellerive said. “What’s not been fully elucidated is the risk that these novel therapies present to these already immunocompromised patients.”

The algorithm was designed to optimize patient safety, ensure appropriate intervention in cased of PJP infection, and standardize the process processes associated with monitoring for infection in a growing academic multiple myeloma program.

In preparing to launch the algorithm, investigators collected patient data, including their name, medical registered number, state and provide, and their PJP diagnosis date, as well as the date of their last infectious disease consults. If the patient received CAR T-cell therapy, the product they received, and date of treatment administration were recorded. If the patient underwent stem cell transplant, the transplant date was recorded, and if it was an allogeneic transplant, the type was recorded as well.

Nurses also collected patient prophylaxis data. This included the patient’s last 2 CD4 values with dates. These values needed to be assessed at least one month apart from the other. They also took note of the date of the patient’s last trimethoprim-sulfamethoxazole (TMP-SMX) refill, their last pentamidine infusion or inhalation, and the last date of dapsone or atovaquone refill, along with the next scheduled laboratory date and any standing lymphocyte subset panels or CD4 orders. The nurses used this data to create the algorithm.

Bellerive noted that the previous practice in her institution was to continue CD4 monitoring while the patients was on prophylaxis, but that there has been a shift to discontinue that practice because of associated costs.

“There is substantial research [that points to] trending benefit of this [monitoring]; [however,] the cost of a CD4 lab at Huntsman exceeds $1500—regardless of insurance provider,” she said. “Because of this, we determined that if a patient is on prophylaxis, we discontinue monitoring the CD4 until the patient meets criteria for resumption per the algorithm.”

Moving forward, Bellerive recommends developing a consensus across academic institutions to establish best practices for CD4 monitoring. As CAR T-cell therapies and bispecific continue to be investigated and approved for patients with multiple myeloma, algorithms specific to that population are needed.

According to Bellerive, further opportunities to improve care delivery include investigating the utility of CD4 monitoring based on alternate level of care and the impact of monitoring heavily refractory patients not exposed to CAR T or bispecific. Moreover, the use of CD4 monitoring algorithms may also have utility in other hematologic malignancies, and this avenue merits further exploration, noted.

“[As] more refined data related to PJP risk associated with novel therapies [are published, we will continue to document our experiences treating these patients,” she said. “One patient spared from PJP justifies our work,” she concluded.

References

1. Bellerive C. Development of a nursing care pathway for monitoring pneumocystis pneumonia risk in relapsed refractory multiple myeloma. Presented at: 19th International Myeloma Society Annual Meeting; August 25-27, 2022; Los Angeles, CA. NS-004.
2. NCCN. National Comprehensive Cancer Network Guidelines in Oncology. Multiple myeloma, version 5.2022. Accessed September 5, 2022. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf
3. Los-Arcos I, Iacoboni G, Aguilar-Guisado M, et al. Recommendations for screening, monitoring, prevention, and prophylaxis of infections in adult and pediatric patients receiving CAR T-cell therapy: a position paper. Infection. 2021;49(2):215-231. doi:10.1007/s15010-020-01521-5