Treatment Options for Recurrent or Refractory Anaplastic Large Cell Lymphoma

ICE regimen (ifosfamide, carboplatin, and etoposide).[33]

Vinblastine.[34]

Brentuximab vedotin.[35]; [36][Level of evidence B4]

Crizotinib [37] and other ALK inhibitors (e.g., alectinib and ceritinib).[38,39]

Allogeneic or autologous hematopoietic stem cell transplant (HSCT).[40-42]

Vinblastine is active as a single agent in patients with recurrent or refractory anaplastic large cell lymphoma.

Vinblastine is active as a single agent in patients with recurrent or refractory anaplastic large cell lymphoma.

In one study, patients with recurrent or refractory anaplastic large cell lymphoma were treated with vinblastine alone, and the following was observed:[34][Level of evidence C1]

Vinblastine is active as a single agent in patients with recurrent or refractory anaplastic large cell lymphoma. › In one study, patients with recurrent or refractory anaplastic large cell lymphoma were treated with vinblastine alone, and the following was observed:[34][Level of evidence C1]

Vinblastine induced complete remission in 25 of 30 evaluable patients (83%).

Vinblastine is active as a single agent in patients with recurrent or refractory anaplastic large cell lymphoma. › In one study, patients with recurrent or refractory anaplastic large cell lymphoma were treated with vinblastine alone, and the following was observed:[34][Level of evidence C1]

Nine of these 25 patients remained in complete remission, with a median follow-up of 7 years from the end of treatment.

ALK kinase inhibitors are highly active in patients with recurrent anaplastic large cell lymphoma that express the NPM::ALK fusion protein.

ALK kinase inhibitors are highly active in patients with recurrent anaplastic large cell lymphoma that express the NPM::ALK fusion protein.

Crizotinib, a kinase inhibitor that blocks the activity of the NPM::ALK fusion protein, has been evaluated in children and adults with relapsed/refractory anaplastic large cell lymphoma.[45]

ALK kinase inhibitors are highly active in patients with recurrent anaplastic large cell lymphoma that express the NPM::ALK fusion protein. › Crizotinib, a kinase inhibitor that blocks the activity of the NPM::ALK fusion protein, has been evaluated in children and adults with relapsed/refractory anaplastic large cell lymphoma.[45]

Of 26 patients with anaplastic large cell lymphoma who were treated with crizotinib on a pediatric phase I study with a phase II extension, 21 patients achieved complete responses.[37,46][Level of evidence B4]

ALK kinase inhibitors are highly active in patients with recurrent anaplastic large cell lymphoma that express the NPM::ALK fusion protein. › Crizotinib, a kinase inhibitor that blocks the activity of the NPM::ALK fusion protein, has been evaluated in children and adults with relapsed/refractory anaplastic large cell lymphoma.[45]

Although complete responses are common, the duration of therapy remains unclear.[47][Level of evidence C2]

ALK kinase inhibitors are highly active in patients with recurrent anaplastic large cell lymphoma that express the NPM::ALK fusion protein. › Crizotinib, a kinase inhibitor that blocks the activity of the NPM::ALK fusion protein, has been evaluated in children and adults with relapsed/refractory anaplastic large cell lymphoma.[45]

The most common adverse event was neutropenia.[46]

ALK kinase inhibitors are highly active in patients with recurrent anaplastic large cell lymphoma that express the NPM::ALK fusion protein.

Alectinib is a second-generation ALK inhibitor that showed superiority over crizotinib in phase III studies for patients with ALK variants and non-small cell lung cancer.[48]

ALK kinase inhibitors are highly active in patients with recurrent anaplastic large cell lymphoma that express the NPM::ALK fusion protein. › Alectinib is a second-generation ALK inhibitor that showed superiority over crizotinib in phase III studies for patients with ALK variants and non-small cell lung cancer.[48]

In a study of ten patients with relapsed/refractory anaplastic large cell lymphoma, eight achieved objective responses, with six complete responses. Five patients achieved durable remissions (397–925 days at the time of the report) to alectinib as a single agent.[38]

ALK kinase inhibitors are highly active in patients with recurrent anaplastic large cell lymphoma that express the NPM::ALK fusion protein.

Ceritinib, an orally administered, second-generation ALK inhibitor, has been shown to be safe and effective in pediatric patients with ALK-positive tumors whose cancer relapsed. In a phase I dose-finding study, eight patients with anaplastic large cell lymphoma were evaluable for response.[39]

ALK kinase inhibitors are highly active in patients with recurrent anaplastic large cell lymphoma that express the NPM::ALK fusion protein. › Ceritinib, an orally administered, second-generation ALK inhibitor, has been shown to be safe and effective in pediatric patients with ALK-positive tumors whose cancer relapsed. In a phase I dose-finding study, eight patients with anaplastic large cell lymphoma were evaluable for response.[39]

Twenty-five percent of the patients achieved a complete response, and 50% achieved a partial response.

Brentuximab vedotin has been evaluated in adults with anaplastic large cell lymphoma.

Brentuximab vedotin has been evaluated in adults with anaplastic large cell lymphoma.

In a phase II study of adults and adolescents with CD30-positive cancers, patients received a dose of 1.8 mg/kg of brentuximab vedotin every 3 weeks for approximately 1 year. The median age of patients was 52 years (range, 14–76 years). Sixteen of 58 patients (28%) had ALK-positive anaplastic large cell lymphoma, and 42 of 58 patients (72%) had ALK-negative anaplastic large cell lymphoma.[35]

Brentuximab vedotin has been evaluated in adults with anaplastic large cell lymphoma. › In a phase II study of adults and adolescents with CD30-positive cancers, patients received a dose of 1.8 mg/kg of brentuximab vedotin every 3 weeks for approximately 1 year. The median age of patients was 52 years (range, 14–76 years). Sixteen of 58 patients (28%) had ALK-positive anaplastic large cell lymphoma, and 42 of 58 patients (72%) had ALK-negative anaplastic large cell lymphoma.[35]

Complete remission rates of approximately 55% to 60% and partial remission rates of 29% were observed.[35]

Brentuximab vedotin has been evaluated in adults with anaplastic large cell lymphoma. › In a phase II study of adults and adolescents with CD30-positive cancers, patients received a dose of 1.8 mg/kg of brentuximab vedotin every 3 weeks for approximately 1 year. The median age of patients was 52 years (range, 14–76 years). Sixteen of 58 patients (28%) had ALK-positive anaplastic large cell lymphoma, and 42 of 58 patients (72%) had ALK-negative anaplastic large cell lymphoma.[35]

For the 38 patients who achieved a complete remission (28 ALK-negative patients, 10 ALK-positive patients), the 5-year PFS rate was 79%, and the OS rate was 57%. PFS was similar for ALK-positive and ALK-negative patients.[49]

Brentuximab vedotin has been evaluated in adults with anaplastic large cell lymphoma. › In a phase II study of adults and adolescents with CD30-positive cancers, patients received a dose of 1.8 mg/kg of brentuximab vedotin every 3 weeks for approximately 1 year. The median age of patients was 52 years (range, 14–76 years). Sixteen of 58 patients (28%) had ALK-positive anaplastic large cell lymphoma, and 42 of 58 patients (72%) had ALK-negative anaplastic large cell lymphoma.[35]

Sixteen patients (11 ALK-negative patients, 5 ALK-positive patients) remained in remission without the start of new therapy other than consolidative HSCT at 5 or more years from the end of treatment with brentuximab vedotin. Of the five ALK-positive patients who remained in remission, four received an allogeneic HSCT, and one received no therapy other than brentuximab vedotin.[49]

Brentuximab vedotin has been evaluated in children with recurrent or refractory anaplastic large cell lymphoma.

Brentuximab vedotin has been evaluated in children with recurrent or refractory anaplastic large cell lymphoma.

In a phase II study, 17 patients (median age, 11 years) were treated with brentuximab vedotin at a dose of 1.8 mg/kg every 21 days. Twelve patients were ALK positive and five were ALK negative. After treatment with brentuximab vedotin, nine patients then received either autologous or allogeneic transplant.[36][Level of evidence B4]

Brentuximab vedotin has been evaluated in children with recurrent or refractory anaplastic large cell lymphoma. › In a phase II study, 17 patients (median age, 11 years) were treated with brentuximab vedotin at a dose of 1.8 mg/kg every 21 days. Twelve patients were ALK positive and five were ALK negative. After treatment with brentuximab vedotin, nine patients then received either autologous or allogeneic transplant.[36][Level of evidence B4]

The overall response rate was 53% (9 of 17 patients), with a complete response rate of 41% (7 of 17 patients), a partial response rate of 12% (2 of 17 patients), a stable disease rate of 29% (5 of 17 patients), and a progressive disease rate of 18% (3 of 17 patients).

Brentuximab vedotin has been evaluated in children with recurrent or refractory anaplastic large cell lymphoma. › In a phase II study, 17 patients (median age, 11 years) were treated with brentuximab vedotin at a dose of 1.8 mg/kg every 21 days. Twelve patients were ALK positive and five were ALK negative. After treatment with brentuximab vedotin, nine patients then received either autologous or allogeneic transplant.[36][Level of evidence B4]

The median EFS was 4.8 months.

Brentuximab vedotin has been evaluated in children with recurrent or refractory anaplastic large cell lymphoma. › In a phase II study, 17 patients (median age, 11 years) were treated with brentuximab vedotin at a dose of 1.8 mg/kg every 21 days. Twelve patients were ALK positive and five were ALK negative. After treatment with brentuximab vedotin, nine patients then received either autologous or allogeneic transplant.[36][Level of evidence B4]

The OS rate was 93.3% at 24 months.

A retrospective study of patients with relapsed or refractory anaplastic large cell lymphoma who received BFM-type first-line therapy, reinduction chemotherapy, followed by autologous HSCT reported the following:[30][Level of evidence B4]

A retrospective study of patients with relapsed or refractory anaplastic large cell lymphoma who received BFM-type first-line therapy, reinduction chemotherapy, followed by autologous HSCT reported the following:[30][Level of evidence B4]

A 5-year EFS rate of 59% and an OS rate of 77%. However, the outcomes were poor for patients with bone marrow or CNS involvement, relapse during first-line therapy, or CD3-positive anaplastic large cell lymphoma. These patients may benefit from allogeneic transplant.

In a European prospective study of patients with relapsed or refractory anaplastic large cell lymphoma, primary refractory patients received aggressive multiagent chemotherapy and underwent allogeneic HSCT. Relapsed patients with CD3-positive disease received less-intense multiagent chemotherapy and allogeneic HSCT (recommended therapy) or autologous HSCT if no donors were available. Relapsed patients with CD3-negative disease (<1 year from diagnosis) received less-aggressive chemotherapy and autologous HSCT. Relapsed patients with CD3-negative disease (>1 year from diagnosis) received single-agent vinblastine for 2 years.[31] The study demonstrated the following results:

In a European prospective study of patients with relapsed or refractory anaplastic large cell lymphoma, primary refractory patients received aggressive multiagent chemotherapy and underwent allogeneic HSCT. Relapsed patients with CD3-positive disease received less-intense multiagent chemotherapy and allogeneic HSCT (recommended therapy) or autologous HSCT if no donors were available. Relapsed patients with CD3-negative disease (<1 year from diagnosis) received less-aggressive chemotherapy and autologous HSCT. Relapsed patients with CD3-negative disease (>1 year from diagnosis) received single-agent vinblastine for 2 years.[31] The study demonstrated the following results:

For the entire cohort, the 5-year EFS rate was approximately 50%, and the OS rate was 77%.

In a European prospective study of patients with relapsed or refractory anaplastic large cell lymphoma, primary refractory patients received aggressive multiagent chemotherapy and underwent allogeneic HSCT. Relapsed patients with CD3-positive disease received less-intense multiagent chemotherapy and allogeneic HSCT (recommended therapy) or autologous HSCT if no donors were available. Relapsed patients with CD3-negative disease (<1 year from diagnosis) received less-aggressive chemotherapy and autologous HSCT. Relapsed patients with CD3-negative disease (>1 year from diagnosis) received single-agent vinblastine for 2 years.[31] The study demonstrated the following results:

For patients with refractory disease or early relapse, reinduction with multiagent chemotherapy followed by allogeneic HSCT achieved the best results (i.e., long-term EFS rate, 65%).

In a European prospective study of patients with relapsed or refractory anaplastic large cell lymphoma, primary refractory patients received aggressive multiagent chemotherapy and underwent allogeneic HSCT. Relapsed patients with CD3-positive disease received less-intense multiagent chemotherapy and allogeneic HSCT (recommended therapy) or autologous HSCT if no donors were available. Relapsed patients with CD3-negative disease (<1 year from diagnosis) received less-aggressive chemotherapy and autologous HSCT. Relapsed patients with CD3-negative disease (>1 year from diagnosis) received single-agent vinblastine for 2 years.[31] The study demonstrated the following results:

Patients who received autologous HSCT fared much worse (i.e., long-term EFS rate, 25%).

In a European prospective study of patients with relapsed or refractory anaplastic large cell lymphoma, primary refractory patients received aggressive multiagent chemotherapy and underwent allogeneic HSCT. Relapsed patients with CD3-positive disease received less-intense multiagent chemotherapy and allogeneic HSCT (recommended therapy) or autologous HSCT if no donors were available. Relapsed patients with CD3-negative disease (<1 year from diagnosis) received less-aggressive chemotherapy and autologous HSCT. Relapsed patients with CD3-negative disease (>1 year from diagnosis) received single-agent vinblastine for 2 years.[31] The study demonstrated the following results:

Patients who had a late relapse (>1 year from diagnosis) were treated with vinblastine for 2 years and achieved a 5-year EFS rate of 81%.

Several additional studies suggest that allogeneic HSCT may result in better outcomes for patients with refractory/relapsed anaplastic large cell lymphoma.[40,42,44,50]