Non-Hodgkin Lymphoma (NHL) Treatment Regimens: AIDS-Related B-Cell Lymphoma

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NON-HODGKIN LYMPHOMA TREATMENT REGIMENS:

AIDS-Related B-Cell Lymphomas

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

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 non-hodgkin lymphoma (AIDS-Related B-Cell Lymphomas) cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These non-hodgkin lymphoma (AIDS-Related B-Cell Lymphomas) cancer treatment regimens are provided only to supplement the latest treatment strategies.

These Cancer Treatment 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 National Comprehensive Cancer Network 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.

(Revised 1/2017)

© 2017 by Haymarket Media, Inc.

Burkitt Lymphoma1ab

Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

CDE (cyclophosphamide + doxorubicin + etoposide) + rituximab2–4

Days 1–4: Cyclophosphamide 187.5–200mg/m2 IV + doxorubicin 12.5mg/m2 IV + etoposide 60mg/m2 IV

Day 1: Rituximab 375mg/m2 IV just before CDE regimen.

Repeat cycle every 4 weeks for a maximum of 6 cycles.

CODOX-M/IVAC (modified) (cyclophosphamide + vincristine + doxorubicin + high-dose methotrexate alternating with ifosfamide + etoposide + high-dose cytarabine)5–7

Day 1: Cyclophosphamide 800mg/m2 IV, followed by

Days 2–5: Cyclophosphamide 200mg/m2 IV

Day 1: Doxorubicin 40mg/m2 IV

Days 1 and 8: Cycle 1: Vincristine 1.5mg/m2 IV; Cycle 2: Days 1, 8, and 15.

Day 1: MTX 1,200mg/m2 IV over 1 hour, followed by 240mg/m2/hour over 23 hours.

Days 1 and 3: Cytarabine 70mg intrathecally.

Day 1: Rituximab 375mg/m2 IV.

Day 15: MTX 12mg intrathecally.

Alternate with:

Days 1–5: Ifosfamide 1,500mg/m2 IV + etoposide 60mg/m2 IV

Days 1 and 2: Cytarabine 2,000mg/m2 IV every 12 hours for 4 doses

Day 1: Rituximab 375mg/m2 IV

Day 15: MTX 12mg intrathecally.

Dose-adjusted EPOCH (etoposide + prednisone + vincristine + cyclophosphamide + doxorubicin) + rituximab8–10a

Days 1–4: Etoposide 50mg/m2 IV + prednisone 60mg/m2 orally + vincristine 0.4mg/m2 IV + doxorubicin 10mg/m2 IV

Day 1: Rituximab 375mg/m2 IV

Day 5: Prednisone 60mg/m2 orally

Day 5: Cycle 1: Cyclophosphamide 375mg/m2 IV if CD4 cells ≥100/mm3 OR 187mg/m2 IV if CD4 cells <100/mm3.

Cyclophosphamide dose-adjustment (after Cycle 1): If nadir ANC >500/mcL, then increase by 187mg above previous cycle. If nadir ANC <500/mcL, or platelets <25,000/mcL, then decrease by 187mg below previous cycle.

Repeat cycle every 3 weeks.

HyperCVAD (cyclophosphamide

+ vincristine + doxorubicin + dexamethasone alternating with high-dose methotrexate and cytarabine)11–13

Cycles 1, 3, 5, and 7—HyperCVAD

Days 1–3: Cyclophosphamide 300mg/m2 IV every 12 hours for 6 doses, plus mesna 600mg/m2 continuous IV

Days 4 and 11: Vincristine 2mg IV

Day 4: Doxorubicin 50mg/m2 IV.

Days 1–4 and Days 11–14: Dexamethasone 40mg daily.

Cycles 2, 4, 6, 8—High-dose MTX and Cytarabine

Day 1: MTX 1g/m2 IV over 24 hours

Days 2 and 3: Cytarabine 3g/m2 IV every 12 hours for 4 doses.

Repeat every 3 weeks for 8 cycles.

Diffuse large B-cell lymphoma (DLBCL), HHV8-positive DLBCL, NOS, and primary effusion lymphoma1ab

Dose-adjusted EPOCH (etoposide + prednisone + vincristine + cyclophosphamide

+ doxorubicin) + rituximab (preferred)8–10a

Days 1–4: Etoposide 50mg/m2 IV + prednisone 60mg/m2 orally + vincristine 0.4mg/m2 IV + doxorubicin 10mg/m2 IV

Day 1: Rituximab 375mg/m2 IV

Day 5: Prednisone 60mg/m2 orally

Day 5: Cycle 1: Cyclophosphamide 375mg/m2 IV if CD4 cells ≥100/mm3 OR 187mg/m2 IV if CD4 cells <100/mm3.

Cyclophosphamide dose-adjustment (after Cycle 1): If nadir ANC >500/mcL, then increase by 187mg above previous cycle. If nadir ANC <500/mcL, or platelets <25,000/mcL, then decrease by 187mg below previous cycle.

Repeat cycle every 3 weeks.

CDE (cyclophosphamide + doxorubicin + etoposide) + rituximab2–4

Days 1–4: Cyclophosphamide 187.5–200mg/m2 IV + doxorubicin 12.5mg/m2 IV + etoposide 60mg/m2 IV

Day 1: Rituximab 375mg/m2 IV just before CDE regimen.

Repeat cycle every 4 weeks for a maximum of 6 cycles.

CHOP + rituximab13–15c

Option 1—Modified CHOP

Day 1: Cyclophosphamide 375mg/m2 IV + doxorubicin 25mg/m2 IV + vincristine 1.4mg/m2 IV (2mg maximum)

Days 1–5: Prednisone 100mg orally

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 3 weeks for at least 4 cycles, or for 2 cycles after complete response.

Option 2—Standard-dose CHOP

Day 1: Cyclophosphamide 750mg/m2 IV + doxorubicin 50mg/m2 IV + vincristine 1.4mg/m2 IV (2mg maximum)

Days 1–5: Prednisone 100mg orally

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 3 weeks for at least 4 cycles, or for 2 cycles after complete response.

Plasmablastic Lymphoma1ab

CODOX-M/IVAC (modified) (cyclophosphamide + vincristine + doxorubicin + high-dose methotrexate alternating with ifosfamide + etoposide + high-dose cytarabine)5–7

Day 1: Cyclophosphamide 800mg/m2 IV, followed by

Days 2–5: Cyclophosphamide 200mg/m2 IV

Day 1: Doxorubicin 40mg/m2 IV

Days 1 and 8: Cycle 1: Vincristine 1.5mg/m2 IV; Cycle 2: Days 1, 8, and 15.

Day 1: MTX 1,200mg/m2 IV over 1 hour, followed by 240mg/m2/hour over 23 hours.

Days 1 and 3: Cytarabine 70mg intrathecally.

Day 1: Rituximab 375mg/m2 IV.

Day 15: MTX 12mg intrathecally.

Alternate with:

Days 1–5: Ifosfamide 1,500mg/m2 IV + etoposide 60mg/m2 IV

Days 1 and 2: Cytarabine 2,000mg/m2 IV every 12 hours for 4 doses

Day 1: Rituximab 375mg/m2 IV

Day 15: MTX 12mg intrathecally.

Dose-adjusted EPOCH (etoposide + prednisone + vincristine + cyclophosphamide

+ doxorubicin) + rituximab8–10a

Days 1–4: Etoposide 50mg/m2 IV + prednisone 60mg/m2 orally + vincristine 0.4mg/m2 IV + doxorubicin 10mg/m2 IV

Day 1: Rituximab 375mg/m2 IV

Day 5: Prednisone 60mg/m2 orally

Day 5: Cycle 1: Cyclophosphamide 375mg/m2 IV if CD4 cells ≥100/mm3 OR 187mg/m2 IV if CD4 cells <100/mm3.

Cyclophosphamide dose-adjustment (after Cycle 1): If nadir ANC >500/mcL, then increase by 187mg above previous cycle. If nadir ANC <500/mcL, or platelets <25,000/mcL, then decrease by 187mg below previous cycle.

Repeat cycle every 3 weeks.

HyperCVAD (cyclophosphamide + vincristine + doxorubicin + dexamethasone alternating with high-dose methotrexate and cytarabine)11–13

Cycles 1, 3, 5, and 7—HyperCVAD

Days 1–3: Cyclophosphamide 300mg/m2 IV every 12 hours for 6 doses, plus mesna 600mg/m2 continuous IV

Days 4 and 11: Vincristine 2mg IV

Day 4: Doxorubicin 50mg/m2 IV.

Days 1–4 and Days 11–14: Dexamethasone 40mg daily.

Cycles 2, 4, 6, 8—High-dose MTX and Cytarabine

Day 1: MTX 1g/m2 IV over 24 hours

Days 2 and 3: Cytarabine 3g/m2 IV every 12 hours for 4 doses.

Repeat every 3 weeks for 8 cycles.

Primary CNS Lymphoma1b

• Initiate highly active antiretroviral therapy (HAART)

• Even with poorly controlled HIV and/or marginal performance status, consider high-dose methotrexate.

• Consider RT alone for palliation of patients who are not candidates for systemic therapy.

• For select patients with good performance status on HAART, see NCCN Guidelines for CNS cancers.

• Best supportive care.

a Granolocyte colony-stimulating factor (GCSF) should be given to all patients. If patients are CD20-negative, rituximab is not indicated.

b Antiretroviral can be administered safely with chemotherapy, but consider changing HAART to non-protease inhibitor-based or CYP3A4-neutral regimen to minimize interactions with chemotherapy. Any change in antiretroviral therapy should be done in consultation with HIV specialist. Concurrent HAART is associated with higher complete response rates.16

c Standard CHOP is not adequate therapy.1

References

1. NCCN Clinical Practice Guidelines in Oncology™. B-cell Lymphomas. v 1.2017. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed January 4, 2017.

2. Sparano JA, Lee S, Chenmg, et al. Phase II trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's lymphoma: An Eastern Cooperative Oncology Group Trial (E1494). J Clin Oncol. 2004;22:1491–1500.

3. Spina M, Chimienti E, Vaccher E, et al. Long-term follow-up of rituximab and infusional cyclophosphamide, doxorubicin, and etoposide in combination with HAART in HIV related Non-Hodgkin's lymphomas. Blood. 2008;112:Abstract 1467.

4. Spina M, Jaeger U, Sparano JA, et al. Rituximab plus infusional cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin lymphoma: pooled results from 3 phase 2 trials. Blood. 2005;105:1891–1897.

5. Wang ES, Straus DJ, Teruya-Feldstein J, et al. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003;98:1196–1205.

6. Barnes JA, LaCasce AS, Feng Y, et al. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: A retrospective analysis. Ann Oncol. 2011;22:1859–1864.

7. Noy A, Kaplan L, Lee J, et al. Modified dose intensive R-CODOX-M/IVAC for HIV-associated Burkitt (BL) (AMC 048) shows efficacy and tolerability, and predictive potential of IRF4/MUM1 expression. Infectious Agents and Cancer. 2012;7:O14.

8. 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.

9. Barta SK,Lee JY, Kaplan LD, et al. Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. Cancer. 2012;118:3977–3983.

10. Bayraktar UD, Ramos JC, Petrich A, et al. Outcome of patients with relapsed/refractory acquired immune deficiency syndrome-related lymphoma diagnosed 1999-2008 and treated with curative intent in the AIDS Malignancy Consortium. Leuk Lymphoma. 2012;53:2383–2389.

11. 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.

12. Thomas DA, Faderl S, O'Brien S, et al. Chemoimmunotherpy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106:1569–1580.

13. Thomas DA, Kantarjian HM, Cortes J, et al. Long-term outcome after hyper-CVAD and rituximab chemoimmunotherapy for Burkitt (BL) or Burkitt-like (BLL) leukemia/lymphoma and mature B-cell lymphocytic leukemia (ALL). Blood. 2008;112:Abstract 1929.

14. 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.

15. 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.

16. Barta SK, Xue X, Wang D, et al. Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients. Blood. 2013;122(19):3251–3262.


Hematologic Cancer Drug Monographs

Leukemias, Lymphomas, And Other Hematologic Cancers

ADCETRIS ALKERAN ALKERAN FOR INJECTION
ARRANON ARZERRA BELEODAQ
BENDEKA BEXXAR BICNU
BLEOMYCIN BLINCYTO BOSULIF
BUSULFEX CAMPATH CERUBIDINE
CLADRIBINE CLOLAR CYCLOPHOSPHAMIDE
CYTARABINE CYTOXAN INJECTION DACOGEN
DARZALEX DEPOCYT DOXIL
DOXORUBICIN HCL DOXORUBICIN HCL SOLUTION DTIC-DOME
EMPLICITI ERWINAZE EVOMELA
FARYDAK FLUDARA FOLOTYN
GAZYVA GLEEVEC GLEOSTINE
HYDREA ICLUSIG IDAMYCIN
IDAMYCIN PFS IMBRUVICA INTRON A
INTRON A SOLN ISTODAX JAKAFI
KEYTRUDA KYPROLIS LEUKERAN
MARQIBO MATULANE METHOTREXATE FOR INJECTION
METHOTREXATE INJECTION MITOXANTRONE HCL MUSTARGEN
MYLERAN NINLARO ONCASPAR
ONTAK OPDIVO PAMIDRONATE DISODIUM INJECTION
PENTOSTATIN POMALYST PURINETHOL
PURIXAN REVLIMID RITUXAN
SPRYCEL SYNRIBO TABLOID
TARGRETIN TARGRETIN GEL TASIGNA
THALOMID TREANDA TREXALL
TRISENOX UVADEX VALCHLOR
VELCADE VENCLEXTA VESANOID
VIDAZA VINBLASTINE FOR INJECTION VINBLASTINE INJECTION
VINCASAR PFS VUMON ZEVALIN
ZOLINZA ZOMETA ZYDELIG

Data provided by the Monthly Prescribing Reference (MPR) Hematology/Oncology Edition.

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