Chemotherapy and Targeted Therapy

Ifosfamide, carboplatin, and etoposide (ICE).[8]

Ifosfamide and vinorelbine, with or without bortezomib.[9][Level of evidence B4]; [10][Level of evidence C3]

Ifosfamide, gemcitabine, and vinorelbine.[11][Level of evidence C1]

Vinorelbine and gemcitabine.[12]; [13][Level of evidence C2]

Vinorelbine, gemcitabine, and dexamethasone.[14][Level of evidence C1]

Etoposide, prednisolone, ifosfamide, and cisplatin (EPIC).[15]

Cytosine arabinoside, cisplatin, and etoposide (APE).[16]

High-dose methotrexate, ifosfamide, etoposide, and dexamethasone (MIED).[17]

Etoposide, methylprednisolone, high-dose cytarabine, and cisplatin (ESHAP).[18]

Dexamethasone, high-dose cytarabine, and cisplatin (DHAP).[19]

Rituximab (for patients with CD20-positive disease) alone or in combination with second-line chemotherapy.[20]

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy.

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy.

A phase II trial in 102 adults with Hodgkin lymphoma whose disease relapsed after autologous HSCT showed the following:[21-24]

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › A phase II trial in 102 adults with Hodgkin lymphoma whose disease relapsed after autologous HSCT showed the following:[21-24]

A complete remission rate of 34% and a partial remission rate of 40% was observed.[21-23]

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › A phase II trial in 102 adults with Hodgkin lymphoma whose disease relapsed after autologous HSCT showed the following:[21-24]

Patients who achieved a complete remission (n = 34) had a 3-year progression-free survival (PFS) rate of 58% and a 3-year overall survival (OS) rate of 73%, with only 6 of 34 patients proceeding to allogeneic HSCT while in remission.

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › A phase II trial in 102 adults with Hodgkin lymphoma whose disease relapsed after autologous HSCT showed the following:[21-24]

Further follow-up demonstrated a 5-year OS rate of 41% and a PFS rate of 22%. However, patients who achieved a complete remission (38%) had a 5-year OS rate of 64% and a PFS rate of 52%.[24][Level of evidence B4]

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy.

The number of pediatric patients treated with brentuximab vedotin is not sufficient to determine whether they respond differently than adult patients. Clearance and volume of brentuximab vedotin significantly correlates with weight (P < .001), and its area under the curve and C max are lower in children than in adults with weekly dosing.[25]

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy.

The Children’s Oncology Group phase I/II AHOD1221 (NCT01780662) study investigated treatment with brentuximab vedotin and gemcitabine in 46 children and young adults with primary refractory Hodgkin lymphoma or early relapse.[26]

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › The Children’s Oncology Group phase I/II AHOD1221 (NCT01780662) study investigated treatment with brentuximab vedotin and gemcitabine in 46 children and young adults with primary refractory Hodgkin lymphoma or early relapse.[26]

The recommended phase II dose of brentuximab vedotin was 1.8 mg/kg.

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › The Children’s Oncology Group phase I/II AHOD1221 (NCT01780662) study investigated treatment with brentuximab vedotin and gemcitabine in 46 children and young adults with primary refractory Hodgkin lymphoma or early relapse.[26]

Twenty-four of 42 patients (57%; 95% confidence interval [CI], 41%–72%) treated at this dose level experienced a complete response within the first four cycles. Four of 13 patients (31%) with partial response or stable disease had all target lesions with Deauville scores of 3 or less after cycle four. By modern response criteria, these are also complete responses, increasing the complete response to 28 of 42 patients (67%; 95% CI, 51%–80%).

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › The Children’s Oncology Group phase I/II AHOD1221 (NCT01780662) study investigated treatment with brentuximab vedotin and gemcitabine in 46 children and young adults with primary refractory Hodgkin lymphoma or early relapse.[26]

Compared with alternate second-line regimens, brentuximab vedotin with gemcitabine offers the advantage of avoiding agents, such as anthracyclines, alkylators, or epipodophyllotoxins, that are associated with late treatment-related sequelae.

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy.

Several small retrospective studies have evaluated the outcomes of pediatric and young adult patients with refractory or relapsed Hodgkin lymphoma treated with brentuximab vedotin and bendamustine. Overall results demonstrate tolerability, response, and the potential for this combination to serve as a bridge treatment to HSCT.[27,28][Level of evidence C1]

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › Several small retrospective studies have evaluated the outcomes of pediatric and young adult patients with refractory or relapsed Hodgkin lymphoma treated with brentuximab vedotin and bendamustine. Overall results demonstrate tolerability, response, and the potential for this combination to serve as a bridge treatment to HSCT.[27,28][Level of evidence C1]

One study evaluated the outcomes of 32 patients (median age, 16 years) who received up to six cycles of treatment with brentuximab vedotin (1.8 mg/kg) on day 1 and bendamustine (90–120 mg/m2) on days 2 and 3.[27]

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › Several small retrospective studies have evaluated the outcomes of pediatric and young adult patients with refractory or relapsed Hodgkin lymphoma treated with brentuximab vedotin and bendamustine. Overall results demonstrate tolerability, response, and the potential for this combination to serve as a bridge treatment to HSCT.[27,28][Level of evidence C1] › One study evaluated the outcomes of 32 patients (median age, 16 years) who received up to six cycles of treatment with brentuximab vedotin (1.8 mg/kg) on day 1 and bendamustine (90–120 mg/m2) on days 2 and 3.[27]

At the end of treatment, the overall response rate was 81%.

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › Several small retrospective studies have evaluated the outcomes of pediatric and young adult patients with refractory or relapsed Hodgkin lymphoma treated with brentuximab vedotin and bendamustine. Overall results demonstrate tolerability, response, and the potential for this combination to serve as a bridge treatment to HSCT.[27,28][Level of evidence C1] › One study evaluated the outcomes of 32 patients (median age, 16 years) who received up to six cycles of treatment with brentuximab vedotin (1.8 mg/kg) on day 1 and bendamustine (90–120 mg/m2) on days 2 and 3.[27]

The 3-year OS rate was 78.1%, and the 3-year PFS rate was 67%.

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › Several small retrospective studies have evaluated the outcomes of pediatric and young adult patients with refractory or relapsed Hodgkin lymphoma treated with brentuximab vedotin and bendamustine. Overall results demonstrate tolerability, response, and the potential for this combination to serve as a bridge treatment to HSCT.[27,28][Level of evidence C1]

A multicenter study from four academic centers evaluated 29 patients (median age, 16 years) who received a median of three cycles of brentuximab vedotin (1.8 mg/kg) on day 1 and bendamustine (90 mg/m2) on days 1 and 2 of 3-week cycles.[28]

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › Several small retrospective studies have evaluated the outcomes of pediatric and young adult patients with refractory or relapsed Hodgkin lymphoma treated with brentuximab vedotin and bendamustine. Overall results demonstrate tolerability, response, and the potential for this combination to serve as a bridge treatment to HSCT.[27,28][Level of evidence C1] › A multicenter study from four academic centers evaluated 29 patients (median age, 16 years) who received a median of three cycles of brentuximab vedotin (1.8 mg/kg) on day 1 and bendamustine (90 mg/m2) on days 1 and 2 of 3-week cycles.[28]

Nineteen patients (66%) achieved a complete metabolic response, and 23 patients (79%) achieved an objective response.

Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HSCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HSCT consolidation therapy. For more information, see the Treatment of Recurrent Classic HL section in Hodgkin Lymphoma Treatment.There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy. › Several small retrospective studies have evaluated the outcomes of pediatric and young adult patients with refractory or relapsed Hodgkin lymphoma treated with brentuximab vedotin and bendamustine. Overall results demonstrate tolerability, response, and the potential for this combination to serve as a bridge treatment to HSCT.[27,28][Level of evidence C1] › A multicenter study from four academic centers evaluated 29 patients (median age, 16 years) who received a median of three cycles of brentuximab vedotin (1.8 mg/kg) on day 1 and bendamustine (90 mg/m2) on days 1 and 2 of 3-week cycles.[28]

The 3-year posttreatment event-free survival rate was 65%, and the OS rate was 89%.