Table 2.
Pooled odd ratios for grade ≥3 infections with targeted therapies in pediatric population treated for leukemias and lymphomas based on RCTs.
| Targeted Therapy | Comparison | Odds Ratios for Grade ≥ 3 Infections |
|---|---|---|
| Rituximab (R) | Addition of R to revised NHL-BFM-95 protocol for BL [36] | No significant difference |
| R-CHOP versus modified NHL-BFM-90 for DLBCL [25] | No significant difference | |
| Addition of R to standard chemotherapy for DLBCL [31] | No significant difference | |
| Addition of R to standard chemotherapy for CD20-positive ALL [43] | No significant difference | |
| Addition of R to modified FAB/LMB96 for stage III/IV B-NHL [29] | OR 2.73 (95% CI: 1.25 to 5.99; p = 0.006) during second induction for C1 group †. No other significant differences during any other phase and across all groups. | |
| Addition of R to FAB/LMB96-based regimen for PMBCL [30] | No significant difference | |
| Addition of R to CCCG-B-NHL2015 protocol for B-NHL [37] | No significant difference | |
| Gemtuzumab ozogamicin (GO) | Addition of GO to COG-AAML0531 regimen for de novo AML [48] | No significant difference |
| Addition of chemotherapy to GO for r/r AML [49] | No significant difference | |
| Post-consolidation randomization to GO or no further therapy for AML (NOPHO-AML 2004) [50] | No significant difference | |
| Pembrolizumab | N/A | |
| Blinatumomab (BLINA) | BLINA versus consolidation chemotherapy for Ph-negative, high-risk, first-relapse B-ALL [51] | No significant difference ‡ |
| Post-reinduction BLINA versus chemotherapy for high- and intermediate-risk first-relapse B-ALL [52] | OR 0.16 (95% CI: 0.08 to 0.35; p = 0.000002) after cycle 1, and OR 0.07 (95% CI: 0.07 to 0.17; p < 0.05) after cycle 2. | |
| BLINA versus InO for r/r BCP-ALL [53] | No significant difference | |
| Imatinib | Addition of imatinib to chemotherapy for Ph-positive ALL [54] | No significant difference |
| Imatinib plus chemotherapy for Ph-positive ALL compared with the same chemotherapy alone for Ph-negative ALL [55] | OR 10.24 (95% CI: 1.25 to 83.67; p = 0.015) during second reinduction. No other significant differences during any other phase. | |
| Addition of imatinib to chemotherapy for Ph-positive ALL [56] | No significant difference overall. As regards infection subcategories, significant difference for sepsis with OR 0.21 (95% CI: 0.04 to 1.07; p = 0.03) during induction only. | |
| Imatinib versus dasatinib | For Ph-positive ALL [57] | No significant difference |
| Nilotinib | N/A | |
| Crizotinib | Crizotinib versus BV for de novo stage II-IV ALCL [58] | No significant difference |
| Entrectinib | N/A | |
| Larotrectinib | N/A | |
| Tisagenlecleucel | N/A | |
| Inotuzumab ozogamicin (InO) | InO versus BLINA for r/r BCP-ALL [53] | No significant difference |
| Brentuximab vedotin (BV) | Chemotherapy plus BV instead of vincristine for de novo high-risk classical HL [59] | No significant difference |
| Addition of BV to chemotherapy for de novo ALCL [60,61] | No significant difference | |
| BV versus crizotinib for de novo stage II-IV ALCL [58] | No significant difference | |
| Bortezomib | For de novo T-cell ALL and lymphoma [62] | OR 0.24 (95% CI: 0.16 to 0.38; p < 0.05) during induction; OR 0.26 (95% CI: 0.18 to 0.37; p < 0.05) during consolidation; OR 0.34 (95% CI: 0.24 to 0.47; p < 0.05) during delayed intensification. |
| Venetoclax | N/A |
BFM = Berlin-Frankfurt-Münster; CCCG = Chinese Children’s Cancer Group; COG = Children’s Oncology Group; CVAD = cyclophosphamide, vincristine, doxorubicin, and dexamethasone; FAB = French–American–British; LMB = lymphomes malins B; NOPHO = Nordic Society of Pediatric Hematology and Oncology; R-CHOP = cyclophosphamide, doxorubicin hydrochloride (hydroxy-daunorubicin), vincristine sulfate (Oncovin), and prednisone; R-ICE = rituximab, ifosfamide, carboplatin, and etoposide; † Group C1 patients = stage IV disease with marrow involvement >25% and CNS-negative; ‡ Significant higher rates of HGG in blinatumomab arm.