Pulmonary function testing (PFT) prior to chimeric antigen receptor T-cell (CAR-T) therapy is commonly performed, but a recent study suggests it may offer limited value in predicting patient outcomes for those with multiple myeloma. Researchers presented their findings at the Tandem Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR.
The Role of PFT in CAR-T Therapy
CAR-T therapy has become a significant treatment option for multiple myeloma, a cancer affecting plasma cells in the bone marrow. However, pulmonary complications can arise during CAR-T treatment, prompting investigation into whether baseline lung function impacts a patient’s response to therapy or overall survival. The study, led by Muhammad Atif Khan, MD, MS, of the University of Kansas Medical Center, aimed to evaluate the association between pre-treatment PFT results and health outcomes in multiple myeloma patients undergoing CAR-T therapy.
Study Design and Participants
The retrospective study involved patients with multiple myeloma treated with CAR-T therapy across four centers. Two of these centers routinely performed PFT before initiating CAR-T infusion. Patients were divided into two groups: those who underwent PFT ( patients) and those who did not ( patients). Researchers collected data on patient demographics, pre-existing health conditions and prior treatments.
The primary outcomes measured were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR), the development of acute hypoxemic respiratory failure (AHRF), and cytokine release syndrome (CRS).
PFT Parameters Measured
The PFTs measured included forced vital capacity (FVC), which assesses the total amount of air a person can forcibly exhale; forced expiratory volume in 1 second (FEV1), which measures how much air a person can exhale in the first second of forced exhalation; and diffusing capacity for carbon monoxide (DLCO), which evaluates how well oxygen passes from the lungs into the bloodstream.
Comorbidities and Prior Therapies
Analysis of pre-existing conditions, such as smoking history, chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung disease, revealed that these were uncommon and evenly distributed between the two groups. However, prior hematopoietic stem cell transplantation (HSCT) was more frequent in the group that did not undergo PFT ( versus ). Exposure to the drug carfilzomib was also more common in the PFT group ( versus , P=).
Study Findings: Limited Prognostic Value
Despite the differences in prior therapies, the study found no significant difference in overall survival between the groups (hazard ratio [HR] , 95% confidence interval [CI] , P=) or progression-free survival (HR , 95% CI , P=). This suggests that pre-treatment PFT does not reliably predict how long patients will live or how long their disease will remain under control.
While impairment in FVC and FEV1 were not associated with health outcomes, the study did find a statistically significant, though clinically negligible, association between the predicted percentage of DLCO and objective response rate (odds ratio [OR] , 95% CI , P=). Researchers noted that no associations were observed with overall survival, progression-free survival, acute hypoxemic respiratory failure, or cytokine release syndrome.
The researchers did not analyze immune effector cell-associated neurotoxicity syndrome (ICANS) due to limited statistical value and variation in grading.
Implications for Clinical Practice
The study’s findings suggest that routine PFT prior to CAR-T therapy provides limited prognostic value for survival and treatment-related safety outcomes in patients with multiple myeloma. As the investigators concluded, “These findings suggest that routine PFT prior to CAR-T provides limited prognostic value for survival and treatment-related safety outcomes.” Measures such as FVC and FEV1 showed no association with survival or complications.
This research contributes to the growing body of knowledge surrounding CAR-T therapy and helps refine our understanding of which pre-treatment assessments are most valuable for optimizing patient care. Further research may be needed to explore the potential role of DLCO in predicting response to CAR-T therapy, but the current findings suggest that it is not a strong predictor of overall outcomes.
