Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma (ALL) – Adult (Greater than or equal to 18 years old)
Page 1 of 7
This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. Stem Cell Transplant (SCT) guidelines are not included with this algorithm. Leukemia patients should be referred and treated at a Comprehensive Cancer Center
PHILADELPHIA NEGATIVE PRECURSOR B (Pre B) LYMPHOBLASTIC LEUKEMIA/LYMPHOMA CLASSIFICATION Pre B ALL
CD19, CD10 (±), CD20 (±),CD22 (±) MPO (-) TdT (+)
TREATMENT
POST-REMISSION THERAPY/MINIMAL RESIDUAL DISEASE
ASSESSMENT OF RESPONSE
Age greater than or equal to 60 years ● Consider clinical trial: 1 ○ Hyper-CVD plus inotuzumab with or without rituximab Age greater than 30 years to 59 years 1 ● Hyper-CVAD with or without rituximab or ● Consider clinical trial: 1 ○ Hyper-CVAD with ofatumumab or 1 ○ Hyper-CMAD with or without rituximab or ○ Hyper-CVAD with blinatumomab
Yes
Consolidation/Maintenance ● Blinatumomab ●
Complete remission? Salvage therapy clinical trial2 ○ Mini-HCVD inotuzumab ○ Chimeric Antigen Receptor (CAR) T-cell therapies ● Blinatumomab ●
BCR-ABL (-)
No3
Age less than or equal to 30 years ● Augmented BFM or ● Consider clinical trial: 1 ○ Augmented BFM with or without ofatumumab or 1 ○ Hyper-CVAD with ofatumumab or ○ Hyper-CVAD with blinatumomab 1
Hyper-CVD (hyper-fractionated cyclophosphamide, vincristine, dexamethasone) plus inotuzumab; rituximab if CD20 greater than or equal to 20% Hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone); rituximab if CD20 greater than or equal to 20% Hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone); ofatumumab if CD20 greater than or equal to 1% Hyper-CMAD (hyper-fractionated cyclophosphamide, liposomal vincristine (Marqibo®), doxorubicin, dexamethasone); rituximab if CD20 greater than or equal to 10% Augmented BFM, Berlin-Frankfurt-Munster (daunorubicin, vincristine, high dose prednisone, pegylated asparaginase); ofatumumab if CD20 greater than or equal to 1% 2 Leukemia Newsletter: http://www.mdanderson.org/leukemia (Available programs-treatment priorities) 3 Fail after INDUCTION with hyper-CVAD based regimen means no response after 2 cycles of chemotherapy Copyright 2016 The University of Texas MD Anderson Cancer Center
Department of Clinical Effectiveness V4 Approved by the Executive Committee of the Medical Staff on 12/13/2016
Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma (ALL) – Adult (Greater than or equal to 18 years old)
Page 2 of 7
This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. Stem Cell Transplant (SCT) guidelines are not included with this algorithm. Leukemia patients should be referred and treated at a Comprehensive Cancer Center
PHILADELPHIA CHROMOSOME (Ph) POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA TREATMENT
CLASSIFICATION Ph+ ALL
CD19, CD10 (±), CD20 (±),CD22 (±) CD13 (±), CD33 (±) CD117 (-) MPO (-) TdT (+) t(9;22)(q24;q11.2) BCR-ABL (+)
Age greater than or equal to 60 years 1 ● Hyper-CVAD plus dasatinib with or without rituximab or 2 ● Consider clinical trial : 1 ○ Hyper-CVAD plus ponatinib with or without rituximab or ○ Hyper-CMAD plus dasatinib (or imatinib) with or without rituximab1 ○ Blinatumomab plus ponatinib ○ Inotuzumab plus bosutinib Age less than 60 years 1 ● Hyper-CVAD plus dasatinib with or without rituximab or 2 ● Consider clinical trial : 1 ○ Hyper-CVAD plus ponatinib with or without rituximab or ○ Hyper-CVAD plus dasatinib (or imatinib) with or without rituximab1
POST-REMISSION THERAPY
ASSESSMENT OF RESPONSE
Yes
Complete remission?
No3
Consolidation/Maintenance or Allogeneic SCT
Asses ABL mutation status 2 ● Consider clinical trial ● Salvage therapy: ○ Blinatumomab plus ponatinib ○ Hyper-CVAD plus ponatinib ○ Inotuzumab plus bosutinib ○ CAR T-cell therapies
1
Hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone); rituximab if CD20 greater than or equal to 20% Hyper-CMAD (hyper-fractionated cyclophosphamide, liposomal vincristine (Marqibo®), doxorubicin, dexamethasone); rituximab if CD20 greater than or equal to 10% 2 Leukemia Newsletter: http://www.mdanderson.org/leukemia (Available programs-treatment priorities) 3 Fail after INDUCTION with hyper-CVAD based regimen means no response after 2 cycles of chemotherapy
Copyright 2016 The University of Texas MD Anderson Cancer Center
Department of Clinical Effectiveness V4 Approved by the Executive Committee of the Medical Staff on 12/13/2016
Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma (ALL) – Adult (Greater than or equal to 18 years old)
Page 3 of 7
This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. Stem Cell Transplant (SCT) guidelines are not included with this algorithm. Leukemia patients should be referred and treated at a Comprehensive Cancer Center
BURKITT OR BURKITT-LIKE LEUKEMIA/LYMPHOMA TREATMENT
CLASSIFICATION
POST-REMISSION THERAPY
ASSESSMENT OF RESPONSE
Burkitt, Burkitt-like ALL or HIV+ Burkitt
sIg (+), CD20 (+) MPO (-) TdT (-)
Yes ●
BCR-ABL (-) c-myc (+)
●
Consolidation
1
Hyper-CVAD with rituximab Consider clinical trial: ○ Hyper-CVAD with ofatumumab or 1 ○ EPOCH with ofatumumab
t(8;14)(q24.1;q32) t(8:22)(q24;q11) t(2;8)(p12;q24)
Complete remission? Consider clinical trial2 ● Salvage therapy: 1 ○ EPOCH with ofatumumab or ○ CAR T-cell therapies ●
No3
1
Hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) plus rituximab Hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) plus ofatumumab EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) plus ofatumumab 2 Leukemia Newsletter: http://www.mdanderson.org/leukemia (Available programs-treatment priorities) 3 Fail after INDUCTION with hyper-CVAD based regimen means no response after 2 cycles of chemotherapy
Copyright 2016 The University of Texas MD Anderson Cancer Center
Department of Clinical Effectiveness V4 Approved by the Executive Committee of the Medical Staff on 12/13/2016
Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma (ALL) – Adult (Greater than or equal to 18 years old)
Page 4 of 7
This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. Stem Cell Transplant (SCT) guidelines are not included with this algorithm. Leukemia patients should be referred and treated at a Comprehensive Cancer Center
PRECURSOR T LYMPHOBLASTIC LEUKEMIA/LYMPHOMA CLASSIFICATION
TREATMENT
ASSESSMENT OF RESPONSE
POST-REMISSION THERAPY
T ALL
●
Yes Age greater than 30 years 1 ● Hyper-CVAD with nelarabine
●
Complete remission?
CD1(±), CD3 (±), CD5 (±),CD7 (±) CD4 (±), CD8 (±)
No2
Consolidation/Maintenance XRT if mediastinal disease
Consider clinical trial2 ● Salvage therapy ●
MPO (-) TdT (+) BCR-ABL (-)
Age less than or equal to 30 years 1 ● Augmented BFM or 1 ● Hyper-CVAD with nelarabine
Yes Complete remission? No
3
Consolidation/Maintenance
Consider clinical trial2 ● Salvage therapy ●
XRT= radiation therapy 1
Hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) Augmented BFM, Berlin-Frankfurt-Munster (daunorubicin, vincristine, high dose prednisone, pegylated asparaginase) 2 Leukemia Newsletter: http://www.mdanderson.org/leukemia (Available programs-treatment priorities) 3 Fail after INDUCTION with hyper-CVAD based regimen means no response after 2 cycles of chemotherapy Copyright 2016 The University of Texas MD Anderson Cancer Center
Department of Clinical Effectiveness V4 Approved by the Executive Committee of the Medical Staff on 12/13/2016
Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma (ALL) – Adult (Greater than or equal to 18 years old)
Page 5 of 7
This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women.
SUGGESTED READINGS Gökbuget, N., Kelsh, M., Chia, V., Advani, A., Bassan, R., Dombret, H., ... & Hoelzer, D. (2016). Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia. Blood Cancer Journal, 6(9), e473. doi: 10.1038/bcj.2016.84. Jain, N., Lamb, A. E., O'Brien, S., Ravandi, F., Konopleva, M., Jabbour, E., ... & Thomas, D. (2016). Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype. Blood, blood-2015.. doi:10.1182/blood-2015-08-661702. Jabbour, E., Kantarjian, H., Ravandi, F., Thomas, D., Huang, X., Faderl, S., ... & Cortes, J. (2015). Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study. The Lancet Oncology, 16(15), 1547-1555. doi:10.1016/S1470-2045(15)00207-7. Jabbour, E., O'Brien, S., Huang, X., Thomas, D., Rytting, M., Sasaki, K., ... & Pierce, S. (2015). Prognostic factors for outcome in patients with refractory and relapsed acute lymphocytic leukemia treated with inotuzumab ozogamicin, a CD22 monoclonal antibody. American journal of hematology, 90(3), 193-196. doi: 10.1002/ajh.23901. Jabbour, E., O'Brien, S., Konopleva, M., & Kantarjian, H. (2015). New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia. Cancer, 121(15), 2517-2528.. doi: 10.1002/cncr.29383. Jabbour, E., O’Brien, S., Ravandi, F., & Kantarjian, H. (2015). Monoclonal antibodies in acute lymphoblastic leukemia. Blood, 125(26), 4010-4016. doi: 10.1182/blood-2014-08-596403. Kantarjian, H. M., Stein, A. S., Bargou, R. C., Grande Garcia, C., Larson, R. A., Stelljes, M., ... & Jia, C. (2016). Blinatumomab treatment of older adults with relapsed/refractory B‐precursor acute lymphoblastic leukemia: Results from two phase 2 studies. Cancer. doi: 10.1002/cncr.30031. Kantarjian, H., Thomas, D., Jorgensen, J., Jabbour, E., Kebriaei, P., Rytting, M., ... & Rios, M. B. (2012). Inotuzumab ozogamicin, an anti-CD22–calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. The lancet oncology, 13(4), 403-411. doi: 10.1016/S1470-2045(11)70386-2.
Copyright 2016 The University of Texas MD Anderson Cancer Center
Department of Clinical Effectiveness V4 Approved by the Executive Committee of the Medical Staff on 12/13/2016
Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma (ALL) – Adult (Greater than or equal to 18 years old)
Page 6 of 7
This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women.
SUGGESTED READINGS Kantarjian, H., Thomas, D., Jorgensen, J., Kebriaei, P., Jabbour, E., Rytting, M., ... & Faderl, S. (2013). Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia. Cancer, 119(15), 2728-2736. NCCN. Acute Lymphoblastic Leukemia. Version 1.2016. Accessed: December 1, 2016. O'Brien, S., Schiller, G., Lister, J., Damon, L., Goldberg, S., Aulitzky, W., ... & Heffner, L. T. (2013). High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome–negative acute lymphoblastic leukemia. Journal of clinical oncology, 31(6), 676-683. Ravandi, F., O'Brien, S. M., Cortes, J. E., Thomas, D. M., Garris, R., Faderl, S., ... & Verstovsek, S. (2015). Long‐term follow‐up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome–positive acute lymphoblastic leukemia. Cancer, 121(23), 4158-4164.. doi: 10.1002/cncr.29646. Sasaki, K., Jabbour, E. J., Ravandi, F., Short, N. J., Thomas, D. A., Garcia‐Manero, G., ... & Issa, G. C. (2016). Hyper‐CVAD plus ponatinib versus hyper‐CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia: A propensity score analysis. Cancer. doi:10.1002/cncr.30231. Short, N. J., Jabbour, E., Sasaki, K., Patel, K., O'Brien, S. M., Cortes, J. E., ... & Thomas, D. (2016). Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood, blood-2016. doi:10.1182/blood-2016-03-707562. Thomas, D. A., Faderl, S., O'Brien, S., Bueso‐Ramos, C., Cortes, J., Garcia‐Manero, G., ... & Shan, J. (2006). Chemoimmunotherapy with hyper‐CVAD plus rituximab for the treatment of adult Burkitt and Burkitt‐type lymphoma or acute lymphoblastic leukemia. Cancer, 106(7), 1569-1580. Thomas DA, O'Brien S, Faderl S, et al. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B -lineage acute lymphoblastic leukemia. J Clin Oncol, 2010; 28: 3880-3889. Topp, M. S., Gökbuget, N., Stein, A. S., Zugmaier, G., O'Brien, S., Bargou, R. C., ... & Neumann, S. (2015). Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. The Lancet Oncology, 16(1), 57-66. doi: 10.1016/S1470-2045(14)71170-2.
Copyright 2016 The University of Texas MD Anderson Cancer Center
Department of Clinical Effectiveness V4 Approved by the Executive Committee of the Medical Staff on 12/13/2016
Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma (ALL) – Adult (Greater than or equal to 18 years old)
Page 7 of 7
This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women.
DEVELOPMENT CREDITS This practice guideline is based on majority expert opinion of the Leukemia Center Faculty at the University of Texas, MD Anderson Cancer Center. It was developed using a multidisciplinary approach that included input from the following medical oncologists. Michael Andreeff, MD Gautam Borthakur, MD Jan Burger, MD Jorge Cortes, MD Zeev Estrov, MD Alessandra Ferrajoli, MDŦ Emil Freireich, MD Guillermo Garcia-Manero, MD Yoliette Goodman, MBA♦ Firoze Jameel, OCN, RN♦ Elias Joseph Jabbour, MDŦ
Ŧ ♦
Hagop M. Kantarjian, MDŦ Tapan Kadia, MD Michael Keating, MD Marina Konopleva, MD Steven Kornblau, MD Farhad Ravandi-Kashani, MD Mary Beth Rios, RNŦ Michael Rytting, MD Srdan Verstovsek, MD William Wierda, MD
Physician Leads Clinical Effectiveness Development Team
Copyright 2016 The University of Texas MD Anderson Cancer Center
Department of Clinical Effectiveness V4 Approved by the Executive Committee of the Medical Staff on 12/13/2016
