PET projects treatment response in adult Hodgkin's disease

ATLANTA – Patients with a positron-emission tomography–confirmed response to chemotherapy for Hodgkin’s lymphoma can be safely spared from radiotherapy without fear of compromising disease control, suggest results of studies presented at the annual meeting of the American Society of Hematology.

Among patients with Hodgkin’s lymphoma whose PET scans were negative for residual disease following three cycles of ABVD chemotherapy, the progression-free survival among patients who also received involved-field radiotherapy (IFRT) was 94.5% at a median of 48.6 months follow-up, compared with 90.8% of PET-negative patients who were not irradiated (intention-to-treat analysis), reported Dr. John Radford on behalf of the United Kingdom’s National Cancer Research Institute Lymphoma Clinical Studies Group.

"Using PET, it is possible to identify a population of patients with stages IA and IIA Hodgkin’s lymphoma who have an excellent outcome after three cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). Crucially, however, these results have been obtained in the setting of, firstly, quality controlled PET image acquisition, secondly, central review of PET images at the core lab in London, and, thirdly, a comprehensive definition of ‘PET-negative,’ " said Dr. Radford.

He emphasized that longer follow-up is needed to determine what the effect of a PET-directed approach will be on 10- and 20-year survival and cause of death.

In a separate study, investigators led by Dr. Andrea Gallamini of San Croce General Hospital in Cuneo, Italy, found that the standard ABVD regimen is adequate therapy for PET-negative patients, and that the BEACOPP-escalated regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) was effective at rescuing PET-positive patients.

RAPID results

Dr. Radford reported results of the RAPID trial (Randomized Phase III Trial to Determine the Role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease).

The goal of the trial was to determine whether a negative PET scan is a good enough biomarker for response to therapy in patients with early-stage Hodgkin’s lymphoma to allow clinicians to safely omit IFRT.

They treated 602 adults with newly diagnosed Hodgkin’s lymphoma (139 of whom had stage IA disease and 281 with stage IIA disease) with three cycles of ABVD and then reassessed them for clinical response. Patients determined to have a response then underwent PET scans, and those who were PET positive went on to a fourth cycle of ABVD and IFRT. PET-negative patients were randomized to either IFRT at 30 Gy, or to no further treatment.

Of the 426 PET-negative patients, 420 were randomized – 209 to IFRT, and 211 to no additional therapy (3 patients chose not to be randomized, clinicians elected not to randomize 2, and 1 patient was not randomized due to an error).

Additionally, 25 PET-negative patients assigned to IFRT did not receive it, due to patient choice (19), deaths (5), or pneumonia (1).

In an intention-to-treat analysis, the hazard ratio for 3-year progression-free survival for PET-negative patients who also received IFRT was 1.51, but it was not statistically significant (P = .23)

In a per-protocol analysis of patients who received the allocated treatment (28 excluded for various reasons from the 420 randomized), the 3-year progression-free survival was 97% in the IFRT arm, and 90.7% in the no-further-treatment arm (HR in favor of IFRT 2.39, P equals .03). Dr. Radford noted, however, that in both the intention-to-treat and per-protocol analyses, the no-IFRT arm fell within the prespecified noninferiority margin.

Treatment intensification

Dr. Gallamini reported the first interim analysis of the GITIL/FIL (Gruppo Italiano Terapie Innovative Nei Linfomi/Fondazione Italiana Linfomi) HD0607 trial, in which patients with Hodgkin’s lymphoma who were PET positive after two cycles of ABVD were then randomized to escalated BEACOPP with or without rituximab. Patients who were PET negative continued on four additional cycles of ABVD.

Among 221 of 485 patients with at least 2-years of follow-up, the failure-free survival rate was 96.9% for patients who were PET negative after two cycles of ABVD compared with 82.7% for those who were PET negative (P less than .001)

"These results, although preliminary, show that a PET-adapted responsive treatment strategy is feasible in a multicenter prospective clinical trial, Dr. Gallamini said.

He added that the standard ABVD regimen appears to be sufficient for patients who are PET negative after two cycles.

The RAPID trial was supported by the UK National Health Service. Dr. Radford reported no relevant disclosures. The HD0607 trial is supported by the Italian Lymphoma Foundation. Dr. Gallamini reported serving on an advisory committee for Seattle Genetics Inc.

ATLANTA – Patients with a positron-emission tomography–confirmed response to chemotherapy for Hodgkin’s lymphoma can be safely spared from radiotherapy without fear of compromising disease control, suggest results of studies presented at the annual meeting of the American Society of Hematology.

Among patients with Hodgkin’s lymphoma whose PET scans were negative for residual disease following three cycles of ABVD chemotherapy, the progression-free survival among patients who also received involved-field radiotherapy (IFRT) was 94.5% at a median of 48.6 months follow-up, compared with 90.8% of PET-negative patients who were not irradiated (intention-to-treat analysis), reported Dr. John Radford on behalf of the United Kingdom’s National Cancer Research Institute Lymphoma Clinical Studies Group.

"Using PET, it is possible to identify a population of patients with stages IA and IIA Hodgkin’s lymphoma who have an excellent outcome after three cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). Crucially, however, these results have been obtained in the setting of, firstly, quality controlled PET image acquisition, secondly, central review of PET images at the core lab in London, and, thirdly, a comprehensive definition of ‘PET-negative,’ " said Dr. Radford.

He emphasized that longer follow-up is needed to determine what the effect of a PET-directed approach will be on 10- and 20-year survival and cause of death.

In a separate study, investigators led by Dr. Andrea Gallamini of San Croce General Hospital in Cuneo, Italy, found that the standard ABVD regimen is adequate therapy for PET-negative patients, and that the BEACOPP-escalated regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) was effective at rescuing PET-positive patients.

RAPID results

Dr. Radford reported results of the RAPID trial (Randomized Phase III Trial to Determine the Role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease).

The goal of the trial was to determine whether a negative PET scan is a good enough biomarker for response to therapy in patients with early-stage Hodgkin’s lymphoma to allow clinicians to safely omit IFRT.

They treated 602 adults with newly diagnosed Hodgkin’s lymphoma (139 of whom had stage IA disease and 281 with stage IIA disease) with three cycles of ABVD and then reassessed them for clinical response. Patients determined to have a response then underwent PET scans, and those who were PET positive went on to a fourth cycle of ABVD and IFRT. PET-negative patients were randomized to either IFRT at 30 Gy, or to no further treatment.

Of the 426 PET-negative patients, 420 were randomized – 209 to IFRT, and 211 to no additional therapy (3 patients chose not to be randomized, clinicians elected not to randomize 2, and 1 patient was not randomized due to an error).

Additionally, 25 PET-negative patients assigned to IFRT did not receive it, due to patient choice (19), deaths (5), or pneumonia (1).

In an intention-to-treat analysis, the hazard ratio for 3-year progression-free survival for PET-negative patients who also received IFRT was 1.51, but it was not statistically significant (P = .23)

In a per-protocol analysis of patients who received the allocated treatment (28 excluded for various reasons from the 420 randomized), the 3-year progression-free survival was 97% in the IFRT arm, and 90.7% in the no-further-treatment arm (HR in favor of IFRT 2.39, P equals .03). Dr. Radford noted, however, that in both the intention-to-treat and per-protocol analyses, the no-IFRT arm fell within the prespecified noninferiority margin.

Treatment intensification

Dr. Gallamini reported the first interim analysis of the GITIL/FIL (Gruppo Italiano Terapie Innovative Nei Linfomi/Fondazione Italiana Linfomi) HD0607 trial, in which patients with Hodgkin’s lymphoma who were PET positive after two cycles of ABVD were then randomized to escalated BEACOPP with or without rituximab. Patients who were PET negative continued on four additional cycles of ABVD.

Among 221 of 485 patients with at least 2-years of follow-up, the failure-free survival rate was 96.9% for patients who were PET negative after two cycles of ABVD compared with 82.7% for those who were PET negative (P less than .001)

"These results, although preliminary, show that a PET-adapted responsive treatment strategy is feasible in a multicenter prospective clinical trial, Dr. Gallamini said.

He added that the standard ABVD regimen appears to be sufficient for patients who are PET negative after two cycles.

The RAPID trial was supported by the UK National Health Service. Dr. Radford reported no relevant disclosures. The HD0607 trial is supported by the Italian Lymphoma Foundation. Dr. Gallamini reported serving on an advisory committee for Seattle Genetics Inc.

ATLANTA – Patients with a positron-emission tomography–confirmed response to chemotherapy for Hodgkin’s lymphoma can be safely spared from radiotherapy without fear of compromising disease control, suggest results of studies presented at the annual meeting of the American Society of Hematology.

Among patients with Hodgkin’s lymphoma whose PET scans were negative for residual disease following three cycles of ABVD chemotherapy, the progression-free survival among patients who also received involved-field radiotherapy (IFRT) was 94.5% at a median of 48.6 months follow-up, compared with 90.8% of PET-negative patients who were not irradiated (intention-to-treat analysis), reported Dr. John Radford on behalf of the United Kingdom’s National Cancer Research Institute Lymphoma Clinical Studies Group.

"Using PET, it is possible to identify a population of patients with stages IA and IIA Hodgkin’s lymphoma who have an excellent outcome after three cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). Crucially, however, these results have been obtained in the setting of, firstly, quality controlled PET image acquisition, secondly, central review of PET images at the core lab in London, and, thirdly, a comprehensive definition of ‘PET-negative,’ " said Dr. Radford.

He emphasized that longer follow-up is needed to determine what the effect of a PET-directed approach will be on 10- and 20-year survival and cause of death.

In a separate study, investigators led by Dr. Andrea Gallamini of San Croce General Hospital in Cuneo, Italy, found that the standard ABVD regimen is adequate therapy for PET-negative patients, and that the BEACOPP-escalated regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) was effective at rescuing PET-positive patients.

RAPID results

Dr. Radford reported results of the RAPID trial (Randomized Phase III Trial to Determine the Role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease).

The goal of the trial was to determine whether a negative PET scan is a good enough biomarker for response to therapy in patients with early-stage Hodgkin’s lymphoma to allow clinicians to safely omit IFRT.

They treated 602 adults with newly diagnosed Hodgkin’s lymphoma (139 of whom had stage IA disease and 281 with stage IIA disease) with three cycles of ABVD and then reassessed them for clinical response. Patients determined to have a response then underwent PET scans, and those who were PET positive went on to a fourth cycle of ABVD and IFRT. PET-negative patients were randomized to either IFRT at 30 Gy, or to no further treatment.

Of the 426 PET-negative patients, 420 were randomized – 209 to IFRT, and 211 to no additional therapy (3 patients chose not to be randomized, clinicians elected not to randomize 2, and 1 patient was not randomized due to an error).

Additionally, 25 PET-negative patients assigned to IFRT did not receive it, due to patient choice (19), deaths (5), or pneumonia (1).

In an intention-to-treat analysis, the hazard ratio for 3-year progression-free survival for PET-negative patients who also received IFRT was 1.51, but it was not statistically significant (P = .23)

In a per-protocol analysis of patients who received the allocated treatment (28 excluded for various reasons from the 420 randomized), the 3-year progression-free survival was 97% in the IFRT arm, and 90.7% in the no-further-treatment arm (HR in favor of IFRT 2.39, P equals .03). Dr. Radford noted, however, that in both the intention-to-treat and per-protocol analyses, the no-IFRT arm fell within the prespecified noninferiority margin.

Treatment intensification

Dr. Gallamini reported the first interim analysis of the GITIL/FIL (Gruppo Italiano Terapie Innovative Nei Linfomi/Fondazione Italiana Linfomi) HD0607 trial, in which patients with Hodgkin’s lymphoma who were PET positive after two cycles of ABVD were then randomized to escalated BEACOPP with or without rituximab. Patients who were PET negative continued on four additional cycles of ABVD.

Among 221 of 485 patients with at least 2-years of follow-up, the failure-free survival rate was 96.9% for patients who were PET negative after two cycles of ABVD compared with 82.7% for those who were PET negative (P less than .001)

"These results, although preliminary, show that a PET-adapted responsive treatment strategy is feasible in a multicenter prospective clinical trial, Dr. Gallamini said.

He added that the standard ABVD regimen appears to be sufficient for patients who are PET negative after two cycles.

The RAPID trial was supported by the UK National Health Service. Dr. Radford reported no relevant disclosures. The HD0607 trial is supported by the Italian Lymphoma Foundation. Dr. Gallamini reported serving on an advisory committee for Seattle Genetics Inc.