Anticancer agent: alkylating (Bendamustine), prolonged steroids (≥20mg/d prednisone x4wk or equivalent), antimetabolite (fludarabine, clofarabine, nelarabine, cladribine; if prolonged lymphopenia), BTKi (Ibrutinib, Acalabrutinib, Zanubrutinib, Pirtobrutinib), PI3Ki (Inavolisib, Copanlisib, Duvelisib, Idelalisib, Umbralisib), mTOR (Everolimus, Sirolimus, Temsirolimus), JAKi (Momelotinib, Ruxolitinib, Fedratinib, Pacritinib),
BiTE (Blinatumomab, Teclistamab-cgyv, Elranatamab-bcmm, Epcoritamab-bysp, Glofitamab-gxbm, Mosunetuzumab-axgb, Talquetamab-tgvs), antiCD20 (Rituximab, Obinutuzumab, Ofatumumab), antiCD30 (Brentuximab vedotin), antiCD33 (Gemtuzumab ozogamicin),
antiCD38 (Daratumumab, Isatuximab), antiCD52 (Alemtuzumab), CCR4 (Mogamulizumab), IL6i (Tocilizumab, Siltuximab), ADC (Polatuzumab vedotin-piiq), ICI CTLA4i (Ipilumumab, Tremelimumab-actl), ICI PD1i (Nivolumab, Pembrolizumab, Cemiplimab-rwlc, Dostarlimab-gxly, Retifanlimab-dlwr, Toripalimab-tpi), ICI PD-L1i (Atezolizumab, Durvalumab, Avelumab), CAR T-cell CD19 (Axi-cel, Brex-cel, Tisa, Liso-cel),
CAR T-cell BCMA (Ide-cel, Cilta-cel)
PJP high risk: allo-SCT, CAR T-cell therapy, ALL, Alemtuzumab, PI3Ki±R, prolonged steroids (prednisone ≥20mg/day for ≥4weeks or equivalent), temozolomide + RT, purine analog therapies, T-cell-depleting agents, autoSCT
Recommend PJP ppx: BiTE (Teclistamab-cgyv, Elranatamab-bcmm, Epcoritamab-bysp, Glofitamab-gxbm, Mosunetuzumab-axgb, Talquetamab-tgvs), antiCD52 if CD4<200 (Alemtuzumab), CCR4 (Mogamulizumab), CAR T-cell CD19 (Axi-cel, Brex-cel, Tisa, Liso-cel), CAR T-cell BCMA (Ide-cel, Cilta-cel)
Consider PJP ppx: BTKi (Ibrutinib, Acalabrutinib, Zanubrutinib, Pirtobrutinib), PI3Ki (Inavolisib, Copanlisib, Duvelisib, Idelalisib, Umbralisib),
mTOR (Everolimus, Sirolimus, Temsirolimus), JAKi (Momelotinib, Ruxolitinib, Fedratinib, Pacritinib), BiTE (Blinatumomab), antiCD20 (Rituximab, Obinutuzumab, Ofatumumab), antiCD30 (Brentuximab vedotin), antiCD38 (Daratumumab, Isatuximab), ADC (Polatuzumab vedotin-piiq),
ICI CTLA4i (Ipilumumab, Tremelimumab-actl), ICI PD1i (Nivolumab, Pembrolizumab, Cemiplimab-rwlc, Dostarlimab-gxly, Retifanlimab-dlwr, Toripalimab-tpi), ICI PD-L1i (Atezolizumab, Durvalumab, Avelumab), anticipated neutropenia ≥7 days (≤500, or ≤1000 with ≤500 in 48h)
Choice of medication: TMP/SMX TMP/SMX desensitization Atovaquone, dapsone and pentamidine (aerosolized or IV)
| Medication | ADE and Clinical Pearls |
| Trimethoprim/ sulfamethoxazole (TMP/SMX) PO [Antibiotic] First line for PJP | Additional activity: Toxoplasma gondii, Nocardia, Listeria, some gram-positive and gram-negative bacteria Dose ppx: SS/day or DS 3 times per week Dose ttt: 15 mg/kg/d (TMP component) in divided doses q6–8h ADE: hemolysis (if G6PD deficiency), false creatinine elevation (due to tubular secretion inhibition), photosensitivity Monitor for renal insufficiency, myelosuppression, hepatotoxicity, and hyperkalemia. DDI with MTX Meta-analysis (12 RCT, N=1245, acute leukemia or HCT patients): reduced PJP occurrence by 91% (RR 0.09; 95% CI 0.02-0.32) and PJP-related mortality (RR 0.17; 95% CI 0.03-0.94). |
| Dapsone PO [Antibiotic] | Additional activity: Toxoplasma gondii Dose ppx: 100mg/day in 1-2 divided doses With weekly pyrimethamine and leucovorin: 50mg/day200mg weekly with weekly pyrimethamine and leucovorinHIV: continue until CD4 ≥200 cells/mm3 for ≥3 months in response to ART; may consider discontinuation in CD4 100-200 cells/mm3 who are receiving ART and have undetectable viral load for ≥3 to 6 monthsSolid txp recipients: ≥6-12 months per organ transplanted, immunosuppression, institutional protocol Dose ttt (mild-moderate): 100mg/day with TMP for 21 days ADE: hemolysis (if G6PD deficiency), blood dyscrasias (methemoglobinemia, hemolytic anemia, neutropenia, agranulocytosis; rarely aplastic anemia and pancytopenia), hepatotoxicity, DRESS (HLA-B*13:01 allele) |
| Atovaquone PO [Antiprotozoal] | Additional activity: Toxoplasma gondii Dose ppx: 1.5 g/day with high-fat meal to enhance absorption HIV: continue following ART initiation until CD4 ≥200 cells/mm3 for ≥3 months; may consider discontinuation in CD4 100-200 cells/mm3 receiving ART and have undetectable viral load for ≥3-6mo Dose ttt (mild-moderate): 750mg BID for 21 days. Can be used in pediatrics if TMP/SMX intolerable ADE: GI upset (nausea, diarrhea), rash, headache, elevated LFTs (rarely). $$$ |
| Pentamidine IV/inhalation [Antifungal, antiprotozoal] | Dose ppx (inhalation/IV): Inhaled form does not protect against extrapulmonary PJP (e.g., CNS), IV is preffered HIV: 300 mg q4wk via Respirgard II nebulizer. Continue after ART initiation until CD4 ≥200 cells/mm3 for ≥3 months; may consider discontinuation in CD4 100-200 cells/mm3 who are receiving ART and have undetectable viral load for ≥3 to 6 months.Immunocompromised, solid organ txp, cancer, HSCT) (off-label use): 300 mg q3-4 weeks via Respirgard II nebulizer Dose ttt (IV): 4 mg/kg/d for 21 days; may reduce to 2-3 mg/kg/day if toxicity occurs ADE (inhaled): Cough, bronchospasm (consider pre-treatment with bronchodilator), metallic taste, rarely pneumothorax ADE (IV): nephrotoxicity, hypotension, electrolyte abnormalities (hypoglycemia → hyperglycemia), bone marrow suppression, arrhythmias, pancreatitis Monitoring: renal function, blood glucose, electrolytes (K, Ca), LFTs |
Duration of PJP Prophylaxis
| Disease/Therapy | Duration |
| Allo-SCT (category 1) CAR T-cell therapy | 6 months and while receiving IST |
| Acute lymphoblastic leukemia (ALL) (category 1) | Throughout antileukemic therapy |
| Alemtuzumab | ≥2 months after Alemtuzumab and until CD4 >200 cells/mcL |
| PI3Ki (copanlisib, idelalisib, or duvelisib) ±R Prolonged steroids (prednisone ≥20mg/day for ≥4weeks or equivalent) Temozolomide + RT | At least throughout treatment |
| Purine analog therapies (fludarabine, cladribine, category 2B) T-cell-depleting agents (category 2B) | Until CD4 >200 cells/mcL |
| AutoSCT | 3-6 months after transplant |