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AIDS-Related B-Cell Lymphomas |
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Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. |
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Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. |
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Note: All recommendations are category 2A unless otherwise indicated. |
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▶Burkitt Lymphoma1,2,a,n |
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REGIMEN |
DOSING |
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Low-Risk Disease |
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Preferred Regimens |
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CODOX-M (Modified) (Cyclophosphamide + Vincristine + Doxorubicin + High-Dose Methotrexate) + Rituximab3-5,b-i |
Days 1-2: Cyclophosphamide 800mg/m2 IV over 30 minutes daily Days 1,8: Vincristine 1.4mg/m2 (maximum 2 mg) IV over 5-10 minutes Day 1: Doxorubicin 50mg/m2 IV push Day 15: Methotrexate 3,000mg/m2 IV over 4 hours Leucovorin: 200mg/m2 IV over 30 minutes starting 24 hours from the initiation of Methotrexate infusion, followed by: Leucovorin: 25mg/m2 IV over 15 minutes OR orally every 6 hours (until Methotrexate serum concentration is <0.05 micromol/L) Day 1: Rituximab 375mg/m2 IV Day 1: Cytarabine 50mg intrathecal OR intraventricular Day 1: Methotrexate 12mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or when post-nadir ANC is ≥1000 cells/mm3) for 3 cycles. |
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SC-EPOCH-RR (Short-Course-Etoposide + Prednisone + Vincristine + Cyclophosphamide + Doxorubicin) + Dose-Dense Rituximab3,4,6-8,b-g,j |
Days 1-4 (Cycle 1): Etoposide 50mg/m2 IV continuous infusion over 24 hours daily, followed by: Days 1-4 (Cycle 2 and Beyond): Etoposide IV continuous infusion over 24 hour daily (dosing based on absolute neutrophil count and platelet nadir measurements during the previous cycle), with: Days 1-4: Vincristine 0.4mg/m2 IV continuous infusion over 24 hours daily, with: Days 1-4 (Cycle 1): Doxorubicin 10 mg/m2 IV continuous infusion over 24 hours daily, followed by: Days 1-4 (Cycle 2 and Beyond): Doxorubicin IV continuous infusion over 24 hours daily (dosing based on absolute neutrophil count and platelet nadir measurements during the previous cycle) Day 5 (Cycle 1): Cyclophosphamide 750mg/m2 IV over 30 minutes, followed by: Day 5 (Cycle 2 and Beyond): Cyclophosphamide IV over 30 minutes (dosing based on absolute neutrophil count and platelet nadir measurements during the previous cycle) Days 1-5: Prednisone 60mg/m2 orally twice daily Day 1,5 (Cycles 1-3): Rituximab 375mg/m2 IV. Repeat cycle every 3 weeks for 3 cycles (if interim PET scan after 2 cycles is negative). |
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Other Recommended Regimens |
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R-Hyper CVAD3,4,9,b-i,k |
Cycle A Days 1-3: Cyclophosphamide 300mg/m2 IV over 2 hours every 12 hours for 6 doses Days 1-3: Mesna 600mg/m2 IV continuous infusion over 24 hours daily starting 1 hour before the first dose of Cyclophosphamide and completing 12 hours after the last dose of Cyclophosphamide Days 4,11: Vincristine 2mg IV over 5-10 minutes Day 4: Doxorubicin 50mg/m2 IV continuous infusion over 24 hours Days 1-4,11-14: Dexamethasone 40mg IV OR orally daily Day 1: Rituximab 375mg/m2 IV Day 2: Methotrexate 12mg intrathecal OR intraventricular Day 7: Cytarabine 100mg intrathecal OR intraventricular. Repeat cycle A every 3 weeks (or earlier if count recovery occurs: maximum of 14 days) for 4 cycles alternating with cycle B. Cycle B Day 1: Methotrexate 200mg/m2 IV over 2 hours, immediately followed by: Day 1: Methotrexate 800mg/m2 IV continuous infusion over 22 hours Leucovorin 50mg IV over 15 minutes OR orally starting 12 hours after the completion of Methotrexate, followed by: Leucovorin 15mg IV over 15 minutes OR orally every 6 hours for at least 8 doses (until Methotrexate serum concentration is <0.05 micromol/L) Days 2-3: Cytarabine (age <60 years) 3,000mg/m2 IV over 3 hours for 4 doses OR Cytarabine (age ≥60 years) 1,000mg/m2 IV over 3 hours for 4 doses Day 1: Rituximab 375mg/m2 IV Day 2: Methotrexate 12mg intrathecal OR intraventricular Day 7: Methotrexate 100mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or earlier if count recovery occurs: minimum of 14 days) for 4 cycles alternating with cycle A (A1,B1,A2,B2,A3,B3,A4,A4). |
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High-Risk, CNS-Negative Disease |
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Preferred Regimens |
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CODOX-M (Modified) + R (Cyclophosphamide + Vinristine + Doxorubicin + High-Dose Methotrexate) + Rituximab (Regimen A) alternating with IVAC (Ifosfamide + Etoposide + High-dose Cytarabine; Regimen B) + Rituximab3,4,b-g,l,m |
Regimen A Days 1-2: Cyclophosphamide 800mg/m2 IV over 30 minutes daily Days 1,8: Vincristine 1.4mg/m2 (maximum 2 mg) IV over 5-10 minutes Day 1: Doxorubicin 50mg/m2 IV push Day 15: Methotrexate 3,000mg/m2 IV over 4 hours Leucovorin: 200mg/m2 IV over 30 minutes starting 24 hours from the initiation of Methotrexate infusion, followed by: Leucovorin: 25mg/m2 IV over 15 minutes OR orally every 6 hours (until Methotrexate serum concentration <0.05 micromol/L) Day 1: Rituximab 375mg/m2 IV Day 1: Methotrexate 12mg intrathecal OR intraventricular, with: Day 1: Cytarabine 50mg intrathecal OR intraventricular, with: Day 1: Hydrocortisone 50mg intrathecal OR intraventricular, followed by: Day 3: Cytarabine 50mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or when post-nadir ANC is ≥1000 cells/mm3) for 2 cycles (Cycles 1 and 3) alternating with (Regimen B; Cycles 2 and 4). Regimen B Days 1-5: Ifosfamide 1,500mg/m2 IV continuous infusion over 24 hours daily, with: Days 1-5: Mesna 1,500mg/m2 IV continuous infusion over 24 hours daily Days 1-5: Etoposide 60mg/m2 IV over 60 minutes daily Days 1-2: Cytarabine 2,000mg/m2 IV over 3 hours every 12 hours for 4 doses Day 1: Rituximab 375mg/m2 IV Day 5: Methotrexate 12mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or when post-nadir ANC is ≥1000 cells/mm3) for 2 cycles (Cycles 2 + 4) alternating with CODOX-M+ R (Regimen A). |
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Other Recommended Regimens |
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R-Hyper CVAD3,4,9,b-i,k |
Cycle A Days 1-3: Cyclophosphamide 300mg/m2 IV over 2 hours every 12 hours for 6 doses Days 1-3: Mesna 600mg/m2 IV continuous infusion over 24 hours daily starting 1 hour before the first dose of Cyclophosphamide and completing 12 hours after the last dose of Cyclophosphamide Days 4,11: Vincristine 2mg IV over 5-10 minutes Day 4: Doxorubicin 50mg/m2 IV continuous infusion over 24 hours Days 1-4,11-14: Dexamethasone 40mg IV OR orally daily Day 1: Rituximab 375mg/m2 IV Day 2: Methotrexate 12mg intrathecal OR intraventricular Day 7: Cytarabine 100mg intrathecal OR intraventricular. Repeat cycle A every 3 weeks (or earlier if count recovery occurs: maximum of 14 days) for 4 cycles alternating with cycle B. Cycle B Day 1: Methotrexate 200mg/m2 IV over 2 hours, immediately followed by: Day 1: Methotrexate 800mg/m2 IV continuous infusion over 22 hours Leucovorin 50mg IV over 15 minutes OR orally starting 12 hours after the completion of Methotrexate, followed by: Leucovorin 15mg IV over 15 minutes OR orally every 6 hours for at least 8 doses (until Methotrexate serum concentration is <0.05 micromol/L) Days 2-3: Cytarabine (age <60 years) 3,000mg/m2 IV over 3 hours for 4 doses OR Cytarabine (age ≥60 years) 1,000mg/m2 IV over 3 hours for 4 doses Day 1: Rituximab 375mg/m2 IV Day 2: Methotrexate 12mg intrathecal OR intraventricular Day 7: Methotrexate 100mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or earlier if count recovery occurs: minimum of 14 days) for 4 cycles alternating with cycle A (A1,B1,A2,B2,A3,B3,A4,A4) for a total of 8 cycles. |
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High-Risk, CNS Disease at Baseline |
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Preferred Regimens |
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CODOX-M (Modified) + R (Cyclophosphamide + Vinristine + Doxorubicin + High-Dose Methotrexate) + Rituximab (Regimen A) alternating with IVAC (Ifosfamide + Etoposide + High-dose Cytarabine; Regimen B) + Rituximab3-5,c-i, l,m |
Regimen A Days 1-2: Cyclophosphamide 800mg/m2 IV over 30 minutes daily Days 1,8: Vincristine 1.4mg/m2 (maximum 2 mg) IV over 5-10 minutes Day 1: Doxorubicin 50mg/m2 IV push Day 15: Methotrexate 3,000mg/m2 IV over 4 hours Leucovorin: 200mg/m2 IV over 30 minutes starting 24 hours from the initiation of Methotrexate infusion, followed by: Leucovorin: 25mg/m2 IV over 15 minutes OR orally every 6 hours (until Methotrexate serum concentration <0.05 micromol/L) Day 1: Rituximab 375mg/m2 IV Day 1: Methotrexate 12mg intrathecal OR intraventricular, with: Day 1: Cytarabine 50mg intrathecal OR intraventricular, with: Day 1: Hydrocortisone 50mg intrathecal OR intraventricular, followed by: Day 3: Cytarabine 50mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or when post-nadir ANC is ≥1000 cells/mm3) for 2 cycles (Cycles 1 and 3) alternating with (Regimen B; Cycles 2 and 4). Regimen B Days 1-5: Ifosfamide 1,500mg/m2 IV continuous infusion over 24 hours daily, with: Days 1-5: Mesna 1,500mg/m2 IV continuous infusion over 24 hours daily Days 1-5: Etoposide 60mg/m2 IV over 60 minutes daily Days 1-2: Cytarabine 2,000mg/m2 IV over 3 hours every 12 hours for 4 doses Day 1: Rituximab 375mg/m2 IV Day 5: Methotrexate 12mg intrathecal OR intraventricular, with: Day 1: Cytarabine 50mg intrathecal or intraventricular, with: Day 1: Hydrocortisone 50mg intrathecal or intraventricular, followed by: Days 3,5: Cytarabine 50mg intrathecal OR intraventricular, with: Days 3,5: Hydrocortisone 50mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or when post-nadir ANC is ≥1000 cells/mm3) for 2 cycles (Cycles 2 and 4) alternating with Regimen A (Cycles 1 and 3). |
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Other Recommended Regimens |
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R-Hyper CVAD3,4,9,c-i,k |
Cycle A Days 1-3: Cyclophosphamide 300mg/m2 IV over 2 hours every 12 hours for 6 doses Days 1-3: Mesna 600mg/m2 IV continuous infusion over 24 hours daily starting 1 hour before the first dose of Cyclophosphamide and completing 12 hours after the last dose of Cyclophosphamide Days 4,11: Vincristine 2mg IV over 5-10 minutes Day 4: Doxorubicin 50mg/m2 IV continuous infusion over 24 hours Days 1-4,11-14: Dexamethasone 40mg IV OR orally daily Day 1: Rituximab 375mg/m2 IV Day 2: Methotrexate 12mg intrathecal OR intraventricular Day 7: Cytarabine 100mg intrathecal OR intraventricular. Repeat cycle A every 3 weeks (or earlier if count recovery occurs: maximum of 14 days) for 4 cycles alternating with cycle B. Cycle B Day 1: Methotrexate 200mg/m2 IV over 2 hours, immediately followed by: Day 1: Methotrexate 800mg/m2 IV continuous infusion over 22 hours Leucovorin 50mg IV over 15 minutes OR orally starting 12 hours after the completion of Methotrexate, followed by: Leucovorin 15mg IV over 15 minutes OR orally every 6 hours for at least 8 doses (until Methotrexate serum concentration is <0.05 micromol/L) Days 2-3: Cytarabine (age <60 years) 3,000mg/m2 IV over 3 hours for 4 doses OR Cytarabine (age ≥60 years) 1,000mg/m2 IV over 3 hours for 4 doses Day 1: Rituximab 375mg/m2 IV Day 2: Methotrexate 12mg intrathecal OR intraventricular Day 7: Methotrexate 100mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or earlier if count recovery occurs: minimum of 14 days) for 4 cycles alternating with cycle A (A1,B1,A2,B2,A3,B3,A4,A4) for a total of 8 cycles. |
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▶Primary CNS Lymphoma (see NCCN Central Nervous System Guidelines)1,2,10,a,o-q For select patients with good performance status, see NCCN Guidelines for CNS – Primary CNS Lymphoma.10 ▶Diffuse Large B-Cell Lymphoma, HHV8-positive DLBCL, NOS, or Primary Effusion Lymphoma1,2,a,b |
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CD20-Positive Disease: First-Line Therapy |
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Preferred Regimens |
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Dose-Adjusted EPOCH (Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin) + Rituximab3-5,11.12,c,e-g |
Days 1-4 (Cycle 1): Etoposide 50mg/m2 IV continuous infusion over 24 hours daily, followed by: Days 1-4 (Cycle 2 and Beyond): Etoposide IV continuous infusion over 24 hour daily (dosing for Cycle 2 and beyond based on absolute neutrophil count and platelet nadir measurements during the previous cycle), with: Days 1-4: Vincristine 0.4mg/m2 IV continuous infusion over 24 hours daily, with: Days 1-4 (Cycle 1): Doxorubicin 10mg/m2 IV continuous infusion over 24 hours daily, followed by: Days 1-4 (Cycle 2 and Beyond): Doxorubicin IV continuous infusion over 24 hours daily (dosing for Cycle 2 and beyond based on absolute neutrophil count and platelet nadir measurements during the previous cycle), with: Day 5 (Cycle 1): Cyclophosphamide 750mg/m2 (if baseline CD4 is >200 cells/mm3) IV over 30 minutes OR Cyclophosphamide 375mg/m2 (if baseline CD4 is 50-200 cells/mm3 IV over 30 minutes, OR Cyclophosphamide consider a starting dose of 187.5mg/m2 (if baseline CD4 is <50 cells/mm3) IV over 30 minutes, followed by: Day 5 (Cycle 2 and Beyond): Cyclophosphamide IV over 30 minutes (dosing for Cycle 2 and beyond based on absolute neutrophil count and platelet nadir measurements during the previous cycle) Day 1: Rituximab 375mg/m2 IV Days 1-5: Prednisone 60mg/m2 orally daily Day 1: Methotrexate 12mg intrathecal OR intraventricular (a total of 4 to 8 doses is recommended over the 6 cycles of treatment). Repeat cycle every 3 weeks for 6 cycles. |
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Other Recommended Regimens |
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CHOP (Cyclophosphamide, Doxorubicin, Vincristine/Prednisone) + Rituximab3,4,13,14,c,e-g |
Day 1: Cyclophosphamide 750mg/m2 IV over 30 minutes Day 1: Doxorubicin 50mg/m2 IV push Day 1: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5-10 minutes Day 1-5: Prednisone 100mg orally daily Day 1: Rituximab 375mg/m2 IV Day 1: Methotrexate 12mg intrathecal OR intraventricular, with: Day 1: Cytarabine 50mg intrathecal OR intraventricular, with: Day 1: Hydrocortisone 50mg intrathecal OR intraventricular. Repeat cycle every 3 weeks for 6 cycles. |
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CD20-Negative Disease: First-Line Therapy |
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CHOP Dose-Adjusted EPOCH (Etoposide + Prednisone + Vincristine + Cyclophosphamide + Doxorubicin)11,12,c,f,g |
Days 1-4 (Cycle 1): Etoposide 50mg/m2 IV continuous infusion over 24 hours daily, followed by: Days 1-4 (Cycle 2 and Beyond): Etoposide IV continuous infusion over 24 hour daily (dosing for Cycle 2 and beyond based on absolute neutrophil count and platelet nadir measurements during the previous cycle), with: Days 1-4: Vincristine 0.4mg/m2 IV continuous infusion over 24 hours daily, with: Days 1-4 (Cycle 1): Doxorubicin 10mg/m2 IV continuous infusion over 24 hours daily, followed by: Days 1-4 (Cycle 2 and Beyond): Doxorubicin IV continuous infusion over 24 hours daily (dosing for Cycle 2 and beyond based on absolute neutrophil count and platelet nadir measurements during the previous cycle) Day 5 (Cycle 1): Cyclophosphamide 750mg/m2 (if baseline CD4 is >200 cells/mm3) IV over 30 minutes OR Cyclophosphamide 375mg/m2 (if baseline CD4 is 50-200 cells/mm3 IV over 30 minutes, OR Cyclophosphamide consider a starting dose of 187.5mg/m2 (if baseline CD4 is <50 cells/mm3) IV over 30 minutes, followed by: Day 5 (Cycle 2 and Beyond): Cyclophosphamide IV over 30 minutes (dosing for Cycle 2 and beyond based on absolute neutrophil count and platelet nadir measurements during the previous cycle) Days 1-5: Prednisone 60mg/m2 orally daily Day 1: Methotrexate 12mg intrathecal OR intraventricular (a total of 4 to 8 doses is recommended over the 6 cycles of treatment). Repeat cycle every 3 weeks for 6 cycles. |
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CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)13-15,c,f,g |
Day 1: Cyclophosphamide 750 mg/m2 IV over 30 minutes Day 1: Doxorubicin 50 mg/m2 IV push Day 1: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5-10 minutes. Days 1-5: Prednisone 100mg orally daily Day 1: Methotrexate 12mg intrathecal OR intraventricular, with: Day 1: Cytarabine 50mg intrathecal OR intraventricular, with: Day 1: Hydrocortisone 50mg intrathecal OR intraventricular Repeat cycle every 3 weeks for 6 cycles. |
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Relapsed CD20-Positive Diseaser |
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Bortezomib/ICE + R (Ifosfamide + Carboplatin + Etoposide) + Rituximab (Category 2B)3,4,16,17,e-g,l |
Days 1,8: Bortezomib 1.5mg/m2 subcutaneous OR IV push Day 9: Ifosfamide 5,000mg/m2 IV continuous infusion over 24 hours, with: Day 9: Mesna 5,000mg/m2 IV continuous infusion over 24 hours Day 9: Carboplatin AUC 5 (maximum 750mg) IV over 30 minutes Days 8-10: Etoposide 100mg/m2 IV over 60 minutes daily. Administer for one 4-week cycle, followed by: Days 1,8: Bortezomib 1.5mg/m2 subcutaneous or IV push over 3 – 5 seconds Day 2: Ifosfamide 5,000mg/m2 IV continuous infusion over 24 hours, with: Day 2: Mesna 5,000mg/m2 IV continuous infusion over 24 hours Day 2: Carboplatin AUC 5 IV over 30 minutes Days 1-3: Etoposide 100mg/m2 IV over 60 minutes daily Day 1: Rituximab 375mg/m2 IV. Repeat cycle every 3 weeks for 5 cycles. |
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Relapsed CD20-Negative Diseaser |
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Bortezomib/ICE (Ifosfamide + Carboplatin + Etoposide) (Category 2B)16,17,f,g,l |
Days 1,8: Bortezomib 1.5mg/m2 subcutaneous OR IV push over 3-5 seconds Day 9: Ifosfamide 5,000mg/m2 IV continuous infusion over 24 hours, with: Day 9: Mesna 5,000mg/m2 IV continuous infusion over 24 hours Day 9: Carboplatin AUC 5 (maximum 750 mg) IV over 30 minutes Days 8-10: Etoposide 100mg/m2 IV over 60 minutes daily Administer for one 4-week cycle, followed by: Days 1,8: Bortezomib 1.5mg/m2 subcutaneous or IV push over 3-5 seconds Day 2: Ifosfamide 5,000mg/m2 IV continuous infusion over 24 hours, with: Day 2: Mesna 5,000mg/m2 IV continuous infusion over 24 hours Day 2: Carboplatin AUC 5 (maximum 750mg) IV over 30 minutes Days 1-3: Etoposide 100mg/m2 IV over 60 minutes daily. Repeat cycle every 3 weeks for 5 cycles. |
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▶Plasmablastic Lymphoma1,2,a,s,t |
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Preferred Regimens |
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Dose-Adjusted EPOCH (Etoposide + Prednisone + Vincristine + Cyclophosphamide + Doxorubicin)11,12,c,f,g |
Days 1-4 (Cycle 1): Etoposide 50mg/m2 IV continuous infusion over 24 hours daily, followed by: Days 1-4 (Cycle 2 and Beyond): Etoposide IV continuous infusion over 24 hour daily (dosing for Cycle 2 and beyond based on absolute neutrophil count and platelet nadir measurements during the previous cycle), with: Days 1-4: Vincristine 0.4mg/m2 IV continuous infusion over 24 hours daily, with: Days 1-4 (Cycle 1): Doxorubicin 10mg/m2 IV continuous infusion over 24 hours daily, followed by: Days 1-4 (Cycle 2 and Beyond): Doxorubicin IV continuous infusion over 24 hours daily (dosing for Cycle 2 and beyond based on absolute neutrophil count and platelet nadir measurements during the previous cycle) Day 5 (Cycle 1): Cyclophosphamide 750mg/m2 (if baseline CD4 is >200 cells/mm3) IV over 30 minutes OR Cyclophosphamide 375mg/m2 (if baseline CD4 is 50-200 cells/mm3 IV over 30 minutes), OR Cyclophosphamide consider a starting dose of 187.5 mg/m2 (if baseline CD4 is <50 cells/mm3) IV over 30 minutes, followed by: Day 5 (Cycle 2 and Beyond): Cyclophosphamide IV over 30 minutes (dosing for Cycle 2 and beyond based on absolute neutrophil count and platelet nadir measurements during the previous cycle) Days 1-5: Prednisone 60mg/m2 orally daily Day 1: Methotrexate 12mg intrathecal OR intraventricular (a total of 4 to 8 doses is recommended over the 6 cycles of treatment) Repeat cycle every 3 weeks for 6 cycles. |
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Other Recommended Regimens |
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Modified CODOX-M (Cyclophosphamide + Vincristine + Doxorubicin + High-Dose Methotrexate)/IVAC (Ifosfamide + Etoposide + High-Dose Cytarabine)9,c,d,f-i,l,m |
Regimen A Days 1-2: Cyclophosphamide 800mg/m2 IV over 30 minutes daily Days 1,8: Vincristine 1.4mg/m2 (maximum 2 mg) IV over 5-10 minutes Day 1: Doxorubicin 50mg/m2 IV push Day 15: Methotrexate 3,000mg/m2 IV over 4 hours Leucovorin: 200mg/m2 IV over 30 minutes starting 24 hours from the initiation of Methotrexate infusion, followed by: Leucovorin: 25mg/m2 IV over 15 minutes OR orally every 6 hours (until Methotrexate serum concentration is <0.05 micromoL/L) Day 1: Methotrexate 12mg intrathecal OR intraventricular, with: Day 1: Cytarabine 50 mg intrathecal OR intraventricular, with: Day 1: Hydrocortisone 50mg intrathecal OR intraventricular, followed by: Days 3: Cytarabine 50mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or when post-nadir ANC is ≥1000 cells/mm3) for 2 cycles (Cycles 1 + 3) alternating with Regimen B (Cycles 2 + 4). Regimen B Days 1-5: Ifosfamide 1,500mg/m2 IV continuous infusion over 24 hours daily, with: Days 1-5: Mesna 1,500mg/m2 IV continuous infusion over 24 hours daily Days 1-5: Etoposide 80mg/m2 IV over 60 minutes daily Days 1-2: Cytarabine 2,000mg/m2 IV over 3 hours every 12 hours for 4 doses Day 5: Methotrexate 12mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or when post-nadir ANC is ≥1000 cells/mm3) for 2 cycles (Cycles 2 + 4) alternating with Regimen A (Cycles 1 + 3). |
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Hyper CVAD (Cyclophosphamide + Vincristine + Doxorubicin + High-Dose Methotrexate + Cytarabine)9,18,c,d,f-i,k |
Cycle A Days 1-3: Cyclophosphamide 300mg/m2 IV over 2 hours every 12 hours for 6 doses Days 1-3: Mesna 600mg/m2 IV continuous infusion over 24 hours daily starting 1 hour before the first dose of Cyclophosphamide and completing 12 hours after the last dose of Cyclophosphamide Days 4,11: Vincristine 2mg IV over 5-10 minutes Day 4: Doxorubicin 50 mg/m2 IV continuous infusion over 24 hours Days 1-4, 11-14: Dexamethasone 40mg orally IV OR orally daily Day 2: Methotrexate 12mg intrathecal OR intraventricular Day 7: Cytarabine 100mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or earlier if count recovery occurs: minimum of 14 days) for 4 cycles alternating with Cycle B. Cycle B: Day 1: Methotrexate 200mg/m2 IV over 2 hours, immediately followed by: Day 1: Methotrexate 800mg/m2 IV continuous infusion over 22 hours Leucovorin 50mg IV over 15 minutes OR orally starting 12 hours after completion of Methotrexate, followed by: Leucovorin 15mg over 15 minutes OR orally every 6 hours for at least 8 doses (until Methotrexate serum concentration is <0.05 micromol) Days 2-3: Cytarabine (age <60 years) 3,000mg/m2 IV over 3 hours every 12 hours for 4 doses OR Cytarabine (age ≥60 years) 1,000mg/m2 IV over 3 hours every 12 hours for 4 doses Day 2: Methotrexate 12mg intrathecal or intraventricular Day 7: Cytarabine 100mg intrathecal OR intraventricular. Repeat cycle every 3 weeks (or earlier if count recovery occurs; minimum of 14 days) for a total of 4 cycles alternating with Cycle A (A1, B1, A2, B2, A2, B3, A4. B4) for a total of 8 cycles. |
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a Antiretroviral therapy (ART) can be administered safely with chemotherapy but consultation with an HIV specialist or pharmacist is important to optimize compatibility. With continued development, new ARTs are expected to affect metabolism of or share toxicities with chemotherapy. In general, avoidance of zidovudine, cobicistat, and ritonavir is strongly recommended. Concurrent ART is associated with higher CR rates (Barta SK, Xue X, Wang D, et al. Blood. 2103;122:3251-3262). b If CD4 <50, maximize supportive care and monitor closely for cytopenias and infections while administering lymphoma therapy. c Oral hydration is strongly encouraged with Cyclophosphamide; poorly hydrated patients may need supplemental IV hydration. Patients should attain combined oral and IV hydration of 2,000-3,000mL/day on day of chemotherapy. d Alkaline hydration is required pre- and post-administration of high-dose Methotrexate. e Rituximab: Premedication for infusion reactions is required. The recommended dosing is: diphenhydramine 12.5-50mg IV or orally 30-40 minutes pre-Rituximab AND acetaminophen 650mg orally 30-40 minutes pre-Rituximab. An FDA-approved biosimilar is an appropriate substitute for Rituximab. f This regimen may be associated with a risk of tumor lysis syndrome with the first cycle. Tumor lysis prophylaxis and/or treatment may be indicated. g Regimen should be administered with myeloid growth factor support. h Leucovorin dose should be titrated for delayed methotrexate clearance (<10-fold decrement in serum methotrexate levels per day) or increases in serum creatinine i For leucovorin: The dose listed is based on racemic leucovorin product. LEVOleucovorin is not interchangeable and the product doses are not equivalent. j For R-EPOCH dosing, see Dunleavy K, Pitialuga S, Shovlin M, et al. Low-intensity therapy in adults with Burkitt’s lymphoma. N Engl J Med. 2013;369:1915-1925; Roschewski M, Dunleavy K, Abramson JS, et al. Blood. 2017;130(Suppl_1):Abstract 188. k CNS prophylaxis in the form of both intrathecal and intravenous therapy are part of this regimen. If a patient presents with positive CSF or leptomeningeal involvement, intrathecal therapy should be administered twice weekly unit CSF is negative, then weekly x 1 month, then monthly x 6 months. Although the specific regimen may vary, a suggested regimen is Cytarabine 50mg + Methotrexate 12mg + Hydrocortisone 50mg. l Hydration is required pre-and post-administration of Ifosfamide. m CNS prophylaxis in the form of both intrathecal and intravenous therapy are part of the regimen. If CNS disease is confirmed, treatment should start with either high-dose Methotrexate or IVAC. n For relapse, see second-line therapy for Burkitt lymphoma. o Initiate ART, if not already receiving. p Even with poorly controlled HIV and/or marginal performance status, consider high-dose Methotrexate. (Gupta N, Nolan A, Omuro A, et al. Neuro Oncol. 2017;19:99-108.) q For select patients with good performance status, see NCCN Guidelines for CNS – Primary CNS Lymphoma.10 r For relapse, also see regimens for relapsed/refractory disease for patients with DLBCL.1 s Standard CHOP is not adequate therapy. t For relapse, see second-line therapy without rituximab for patients with DLBCL.1 |
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References |
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1. Referenced with permission from the NCCN Clinical Practice Guidelines in OncologyTM B-Cell Lymphomas Version 5.2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed October 18, 2021. 2. NCC N Guidelines for Cancer in People with HIV. V2.2021. hiv.pdf (nccn.org). Accessed October 25, 2021. 3. Rituximab (Rituxan) [package insert]. South San Francisco, CA: Biogen and Genentech, Inc.;2021. 4. Assouline S, Buccheri V, Delmer A, et al. Pharmacokinetics, safety, and efficacy of subcutaneous versus intravenous rituximab plus chemotherapy as treatment for chronic lymphocytic leukaemia (SAWYER): a phase 1b, open-label, randomized controlled non-inferiority trial. Lancet Haematol. 2016;3(3):e128-138. 5. Noy A, Lee JY, Cesarman E, et al. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015;126:160-166. 6. Dunleavy K, Pittaluga S, Shovlin M, et al. Low-intensity therapy in adults with Burkitt’s lymphoma. N Engl J Med. 2013;369:1915-1925. 7. Dunleavy K, Little RF, Pittaluga S, et al. The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV- associated diffuse large B-cell lymphoma. Blood. 2010;115:3017-3024. 8. Roschewski M, Dunleavy K, Abramson JS, et al. Multicenter study of Risk-adapted therapy with dose-adjusted EPOCH-R in adults with untreated Burkitt lymphoma. J Clin Oncol. 2020;38:2519-2529. 9. Thomas DA, Faderl S, O’Brien S, Bueso-Ramos C, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106:1569-1580. 10. NCCN Central Nervous System Clinical Practice Guidelines. https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf, Accessed October 20, 2021. 11. Little RF, Pittaluga S, Grant N, et al. Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biology. Blood. 2003; 101:4653-4659. 12. Ramos JC, Sparano JA, Rudek MA, et al. Safety and Preliminary Efficacy of Vorinostat With R-EPOCH in High-risk HIV-associated Non-Hodgkin’s Lymphoma (AMC-075). Clin Lymphoma Myeloma Leuk. 2018;18:180-190 e182. 13. Boue F, Gabarre J, Gisselbrecht C, et al. Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin’s lymphoma. J Clin Oncol. 2006;24: 4123-4128. 14. Ribera JM, Oriol A, Morgades M, et al. Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus-associated diffuse large B-cell lymphoma: results of a phase II trial. Br J Haematol. 2008;140:411-419. 15. Kaplan LD, Lee JY, Ambinder RF, et al. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005;106:1538-1543. 16. Reid EG, Looney D, Maldarelli F, et al. Safety and efficacy of an oncolytic viral strategy using bortezomib with ICE/R in relapsed/refractory HIV-positive lymphomas. Blood Adv. 2018;2:3618-3626. 17. Bortozemib (VELCADE)[package insert]. Cambridge, MA: Millennium Pharmaceuticals, Inc.; 2003 18. Cortes J, Thomas D, Rios A, et al. Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia. Cancer. 2002;94:1492-1499. |
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(Revised 11/2021; NCCN B-Cell Lymphomas Guidelines. v5.2021.) © 2021 by Haymarket Media, Inc. |
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