Treatment options for recurrent or refractory Burkitt lymphoma

For improved survival:

For improved survival:

Duration of complete remission of more than 6 months.[38,39]

For improved survival:

Normal LDH levels at initial diagnosis.[38,39]

For improved survival:

One site of disease at relapse.[38]

For improved survival:

No failure in bone marrow.[39]

For improved survival:

Diffuse large B-cell lymphoma histology.[38]

For improved survival:

Complete remission before hematopoietic stem cell transplant (HSCT).[37][Level of evidence C1]

For improved survival:

Reinduction with intensive continuous therapy before HSCT.[37][Level of evidence C1]

For inferior survival:

For inferior survival:

Progression during initial therapy.[37][Level of evidence C1]

For inferior survival:

Rituximab during initial therapy.[37][Level of evidence C1]

R-ICE regimen (rituximab plus ifosfamide, carboplatin, and etoposide [ICE]).[40]

CYVE regimen (high-dose cytarabine and etoposide) for relapsed group A and group B disease.[38]

Allogeneic or autologous HSCT.[41-43]

Bispecific antibody (anti-CD20, anti-CD3) therapy.[44]

Chimeric antigen receptor (CAR) T-cell therapy.[45]

R-VICI regimen (rituximab, vincristine, idarubicin, ifosfamide, carboplatin, and dexamethasone).[37][Level of evidence C1]

A study from the United Kingdom for children with relapsed or refractory mature B-cell NHL and B-cell acute lymphoblastic leukemia reported the following:[46]

A study from the United Kingdom for children with relapsed or refractory mature B-cell NHL and B-cell acute lymphoblastic leukemia reported the following:[46]

The most favorable outcomes occurred in patients who received rituximab and an autologous HSCT.

A study from the United Kingdom for children with relapsed or refractory mature B-cell NHL and B-cell acute lymphoblastic leukemia reported the following:[46]

However, the study could not distinguish whether this relationship reflected that children who survived were those who remained well enough to tolerate chemotherapy and rituximab, achieved a response, and were eligible for transplant.

In a COG study of 20 patients with relapsed/refractory B-cell NHL (Burkitt lymphoma [n = 14] and diffuse large B-cell lymphoma) who were treated with R-ICE, the following was observed:[40][Level of evidence C1]

In a COG study of 20 patients with relapsed/refractory B-cell NHL (Burkitt lymphoma [n = 14] and diffuse large B-cell lymphoma) who were treated with R-ICE, the following was observed:[40][Level of evidence C1]

A complete remission/partial remission rate of 60%.

The Japanese Pediatric Leukemia/Lymphoma Study Group performed a phase II study using R-ICE to treat 28 pediatric patients with relapsed/refractory B-cell NHL.[47]

The Japanese Pediatric Leukemia/Lymphoma Study Group performed a phase II study using R-ICE to treat 28 pediatric patients with relapsed/refractory B-cell NHL.[47]

The investigators observed a complete and partial response rate of 70%.

A retrospective review of patients with relapsed disease treated in the LMB-89, LMB-96, and LMB-2001 trials were analyzed. Group A and group B patients received the CYVE regimen as initial salvage therapy, and group C patients received ICE with or without rituximab.[38]

A retrospective review of patients with relapsed disease treated in the LMB-89, LMB-96, and LMB-2001 trials were analyzed. Group A and group B patients received the CYVE regimen as initial salvage therapy, and group C patients received ICE with or without rituximab.[38]

The complete and partial remission rate was 64%; 2 of 3 group A patients responded, 19 of 29 group B patients responded, and 3 of 5 group C patients responded.

A retrospective review of patients with relapsed Burkitt lymphoma treated initially with BFM therapy noted that patients who were treated before the year 2000 had significantly inferior outcomes compared with those who were treated after 2000. The 5-year overall survival (OS) rates were 11% for those treated before the year 2000, compared with 27% for those treated after 2000. The 75 patients treated after 2000 were analyzed further, with the following results:[37][Level of evidence C1]

A retrospective review of patients with relapsed Burkitt lymphoma treated initially with BFM therapy noted that patients who were treated before the year 2000 had significantly inferior outcomes compared with those who were treated after 2000. The 5-year overall survival (OS) rates were 11% for those treated before the year 2000, compared with 27% for those treated after 2000. The 75 patients treated after 2000 were analyzed further, with the following results:[37][Level of evidence C1]

Of the 75 patients, 29 (41%) had leukemic involvement.

A retrospective review of patients with relapsed Burkitt lymphoma treated initially with BFM therapy noted that patients who were treated before the year 2000 had significantly inferior outcomes compared with those who were treated after 2000. The 5-year overall survival (OS) rates were 11% for those treated before the year 2000, compared with 27% for those treated after 2000. The 75 patients treated after 2000 were analyzed further, with the following results:[37][Level of evidence C1]

Median time to relapse was 0.4 years after diagnosis. More than one-third of patients relapsed during initial treatment.

A retrospective review of patients with relapsed Burkitt lymphoma treated initially with BFM therapy noted that patients who were treated before the year 2000 had significantly inferior outcomes compared with those who were treated after 2000. The 5-year overall survival (OS) rates were 11% for those treated before the year 2000, compared with 27% for those treated after 2000. The 75 patients treated after 2000 were analyzed further, with the following results:[37][Level of evidence C1]

Reinduction therapy was variable; 65% of patients proceeded to either autologous or allogeneic HSCT.

A retrospective review of patients with relapsed Burkitt lymphoma treated initially with BFM therapy noted that patients who were treated before the year 2000 had significantly inferior outcomes compared with those who were treated after 2000. The 5-year overall survival (OS) rates were 11% for those treated before the year 2000, compared with 27% for those treated after 2000. The 75 patients treated after 2000 were analyzed further, with the following results:[37][Level of evidence C1]

Reinduction with intensive continuous chemotherapy with R-VICI therapy before HSCT improved survival (4-year OS rate, 67%).

A retrospective review of patients with relapsed Burkitt lymphoma treated initially with BFM therapy noted that patients who were treated before the year 2000 had significantly inferior outcomes compared with those who were treated after 2000. The 5-year overall survival (OS) rates were 11% for those treated before the year 2000, compared with 27% for those treated after 2000. The 75 patients treated after 2000 were analyzed further, with the following results:[37][Level of evidence C1]

Initial disease risk category was prognostic: Low-risk patients (R1/R2) had improved survival (4-year OS rate, 50%), compared with high-risk patients (R3/R4; 4-year OS rate, 21%).

A retrospective review of patients with relapsed Burkitt lymphoma treated initially with BFM therapy noted that patients who were treated before the year 2000 had significantly inferior outcomes compared with those who were treated after 2000. The 5-year overall survival (OS) rates were 11% for those treated before the year 2000, compared with 27% for those treated after 2000. The 75 patients treated after 2000 were analyzed further, with the following results:[37][Level of evidence C1]

First-line therapy was also prognostic: 25 of 28 patients with progression during first-line therapy died, and 9 of 10 patients who were treated with front-line rituximab died.

A retrospective review of patients with relapsed Burkitt lymphoma treated initially with BFM therapy noted that patients who were treated before the year 2000 had significantly inferior outcomes compared with those who were treated after 2000. The 5-year overall survival (OS) rates were 11% for those treated before the year 2000, compared with 27% for those treated after 2000. The 75 patients treated after 2000 were analyzed further, with the following results:[37][Level of evidence C1]

Complete remission before HSCT was prognostic (4-year OS rate, 63%).

There are limited data for CAR T-cell therapy in pediatric patients with Burkitt lymphoma and diffuse large B-cell lymphoma. A single-center experience included 23 children with relapsed or refractory Burkitt lymphoma who were treated sequentially with three CAR T cells (CD19, CD22, and CD20). Patients were followed every 2 weeks, and they received subsequent CAR T cells if CAR T cells were not detectable in the blood or there was evidence of disease progression.[45]

There are limited data for CAR T-cell therapy in pediatric patients with Burkitt lymphoma and diffuse large B-cell lymphoma. A single-center experience included 23 children with relapsed or refractory Burkitt lymphoma who were treated sequentially with three CAR T cells (CD19, CD22, and CD20). Patients were followed every 2 weeks, and they received subsequent CAR T cells if CAR T cells were not detectable in the blood or there was evidence of disease progression.[45]

The 18-month complete response and PFS rates were 78%.

There are limited data for CAR T-cell therapy in pediatric patients with Burkitt lymphoma and diffuse large B-cell lymphoma. A single-center experience included 23 children with relapsed or refractory Burkitt lymphoma who were treated sequentially with three CAR T cells (CD19, CD22, and CD20). Patients were followed every 2 weeks, and they received subsequent CAR T cells if CAR T cells were not detectable in the blood or there was evidence of disease progression.[45]

These results may be due to short (1 week) CAR T-cell manufacture time and/or sequential antigen targeting.

There are limited data for CAR T-cell therapy in pediatric patients with Burkitt lymphoma and diffuse large B-cell lymphoma. A single-center experience included 23 children with relapsed or refractory Burkitt lymphoma who were treated sequentially with three CAR T cells (CD19, CD22, and CD20). Patients were followed every 2 weeks, and they received subsequent CAR T cells if CAR T cells were not detectable in the blood or there was evidence of disease progression.[45]

The sustained complete response rates were 39% (9 of 23) for CD19 CAR T cells, 38% (5 of 13) for CD22 CAR T cells, and 50% (3 of 6) for CD20 CAR T cells.

There are limited data for CAR T-cell therapy in pediatric patients with Burkitt lymphoma and diffuse large B-cell lymphoma. A single-center experience included 23 children with relapsed or refractory Burkitt lymphoma who were treated sequentially with three CAR T cells (CD19, CD22, and CD20). Patients were followed every 2 weeks, and they received subsequent CAR T cells if CAR T cells were not detectable in the blood or there was evidence of disease progression.[45]

The median follow-up was only 17 months.

An analysis of data from the Center for International Blood and Marrow Transplant Research demonstrated the following:[41]

An analysis of data from the Center for International Blood and Marrow Transplant Research demonstrated the following:[41]

No difference in outcome using either autologous or allogeneic donor stem cell sources.

An analysis of data from the Center for International Blood and Marrow Transplant Research demonstrated the following:[41]

The 2-year EFS rates were 50% for patients with diffuse large B-cell lymphoma and 30% for patients with Burkitt lymphoma who survived to undergo a transplant.

An analysis of data from the Center for International Blood and Marrow Transplant Research demonstrated the following:[41]

Some graft-versus-lymphoma effect has been implied by the lower relapse rate in the allogeneic HSCT patients. However, that effect was balanced by the higher treatment-related mortality.

A small, single-center, prospective study used autologous transplant followed by reduced-intensity allogeneic HSCT to treat patients with relapsed NHL.[42]

A small, single-center, prospective study used autologous transplant followed by reduced-intensity allogeneic HSCT to treat patients with relapsed NHL.[42]

The study reported an EFS rate of 60%.