A33-27 Breakthrough Pneumocystis Jiroveci Pneumonia Despite TMP-SMX Prophylaxis While on Teclistamab

Introduction Teclistamab is a first-in-class, bispecific T-cell engager antibody that was FDA-approved in October 2022 for refractory Multiple Myeloma (MM). Teclistamab simultaneously binds the T-cell CD3 complex and the B-cell Maturation Antigen (BCMA) on plasma cells, leading to T-cell-mediated destruction of the malignant plasma cells. The MajesTEC-1 trial, the key trial for Teclistamab’s FDA approval, noted a higher burden of any-grade infection with this medicine and included a focused safety analysis that reported Pneumocystis jiroveci Pneumonia (PJP) in 4.2% of patients. As with any immunosuppressive medication, appropriate microbial prophylaxis is indicated. We present a case of a patient on Teclistamab for ∼1 year, who required ICU admission and subsequent intubation for acute hypoxic respiratory failure due to PJP, despite adherence to appropriate Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. Case Presentation A 57-year-old male with diastolic heart failure, atrial fibrillation, pulmonary embolism, and Multiple Myeloma (stem cell transplant 2013, receiving Teclistamab and IVIG) presented with four days of progressive weakness, cough, malaise, and dyspnea. A CT chest demonstrated multifocal pneumonia with superimposed pulmonary edema. He was admitted to the ICU for acute hypoxic respiratory failure requiring oxymizer, diuresis, and empiric treatment for hospital-acquired pneumonia. The patient’s respiratory status continued to deteriorate, necessitating intubation. Bedside bronchoscopy revealed diffuse alveolar hemorrhage and cytology consistent with Pneumocystis jiroveci. Therapy was adjusted to treatment-dose TMP-SMX and high-dose steroids, which resulted in marked improvement. The patient ultimately discharged with a 3-week course of TMP-SMX, a steroid taper, and follow-up in Infectious Disease and Pulmonary clinics. Discussion The profound immunosuppression of novel biological agents creates heightened vulnerability for opportunistic infections despite appropriate prophylaxis and emphasizes the necessity to monitor immune system markers beyond the classic CD4 count, such as immunoglobulin levels. This patient had low IgG levels as a consequence of Teclistamab’s profound humoral suppression and T-cell dysregulation/depletion. This degree of immunosuppression was suspected to have allowed the proliferation of PJP in our patient, despite appropriate prophylaxis and IVIG infusion. Treatment with these novel biologics should prompt a low threshold for early bronchoscopy and cytological studies for any opportunistic infections, especially in critically ill patients. Conclusion Clinicians should maintain a high index of suspicion for all opportunistic infections, and low threshold for definitive diagnostic studies, in patients receiving novel and potent biologics, even if patients are adherent to guideline-directed prophylaxis.