In the Journals

OS rate for Hodgkin lymphoma remains high with PET response-adapted therapy

Patients with advanced, persistent Hodgkin lymphoma who switched to an escalated treatment regimen as part of a PET-adapted therapy approach achieved favorable PFS but a high rate of secondary malignancies compared with historical controls, according to 5-year follow-up data from the SWOG S0816 trial published in Blood.

Researchers noted that PET response-adapted therapy led to an estimated 5-year OS rate of 94% among all patients treated on the trial.

“For patients with newly diagnosed Ann Arbor stage III/[stage] IV Hodgkin lymphoma, approximately 70% can expect to be cured after treatment with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD), which has been the preferred standard of care in the United States for many years,” Deborah M. Stephens, DO, physician leader of the hematology clinical trials division at Huntsman Cancer Institute at University of Utah, and colleagues wrote. “An alternate treatment regimen for advanced-stage Hodgkin lymphoma — escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone — has demonstrated a higher cure rate with a trade-off of increased short- and long-term toxicities, including second cancers and infertility. The desire to maximize efficacy and minimize toxicity has prompted concerted efforts to better identify patients at highest risk for shortest survival.”

A key predictor of this risk is interim metabolic response as determined through PET scan after the second cycle of ABVD, which researchers referred to as PET2. Inability to achieve complete response at this point has been linked to significantly shorter PFS. For this reason, clinicians have developed response-adapted therapy, through which PET2 guides the decision to decrease, maintain or increase the intensity of treatment.

In the S0816 trial, patients with newly diagnosed advanced-stage Hodgkin lymphoma underwent two cycles of ABVD. Those who attained complete remission on PET2 received four additional cycles of ABVD, whereas those who did not switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (eBEACOPP).

The primary analysis — conducted after a median 3.3 years of follow-up — showed 2-year PFS of 79% among all patients, which researchers described as excellent.

In the follow-up study, Stephens and colleagues evaluated a subset of 336 patients (median age, 31 years; range, 18-60; 56% men), including 331 with central review of PET2 (82% PET2-negative; 18% PET2-positive).

With median follow-up of 5.9 years (range, 0.2-8.3), researchers estimated 5-year PFS of 74% (95% CI, 69-79) for all patients, 76% (95% CI, 70-81) for PET2-negative patients and 66% (95% CI, 52-76) for PET2-positive patients.

Estimated 5-year OS for all patients was 94% (95% CI, 91-96).

Researchers observed a higher rate of reported second cancers among patients treated with eBEACOPP (14%; n = 7) than among patients treated with ABVD (2%; n = 6; P = .001).

Patients treated on the S0816 trial continue to have high rates of long-term OS, researchers noted. They added, however, that almost 25% of PET2-negative patients experienced relapse, illustrating the limitations of frontline ABVD and underscoring the negative predictive value of PET2.

“In PET2-positive patients who received eBEACOPP, PFS was favorable, but was associated with a high rate of second malignancies compared with historical controls,” Stephens and colleagues wrote. “Our results emphasize the importance of long-term follow-up, and the need for more efficacious and less toxic therapeutic approaches for advanced-stage [patients with] Hodgkin lymphoma.” – by Jennifer Byrne

Disclosures: Stephens reports research funding from Acerta, Gilead and Karyopharm and honoraria from Genentech. Please see the study for all other authors’ relevant financial disclosures.

Patients with advanced, persistent Hodgkin lymphoma who switched to an escalated treatment regimen as part of a PET-adapted therapy approach achieved favorable PFS but a high rate of secondary malignancies compared with historical controls, according to 5-year follow-up data from the SWOG S0816 trial published in Blood.

Researchers noted that PET response-adapted therapy led to an estimated 5-year OS rate of 94% among all patients treated on the trial.

“For patients with newly diagnosed Ann Arbor stage III/[stage] IV Hodgkin lymphoma, approximately 70% can expect to be cured after treatment with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD), which has been the preferred standard of care in the United States for many years,” Deborah M. Stephens, DO, physician leader of the hematology clinical trials division at Huntsman Cancer Institute at University of Utah, and colleagues wrote. “An alternate treatment regimen for advanced-stage Hodgkin lymphoma — escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone — has demonstrated a higher cure rate with a trade-off of increased short- and long-term toxicities, including second cancers and infertility. The desire to maximize efficacy and minimize toxicity has prompted concerted efforts to better identify patients at highest risk for shortest survival.”

A key predictor of this risk is interim metabolic response as determined through PET scan after the second cycle of ABVD, which researchers referred to as PET2. Inability to achieve complete response at this point has been linked to significantly shorter PFS. For this reason, clinicians have developed response-adapted therapy, through which PET2 guides the decision to decrease, maintain or increase the intensity of treatment.

In the S0816 trial, patients with newly diagnosed advanced-stage Hodgkin lymphoma underwent two cycles of ABVD. Those who attained complete remission on PET2 received four additional cycles of ABVD, whereas those who did not switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (eBEACOPP).

The primary analysis — conducted after a median 3.3 years of follow-up — showed 2-year PFS of 79% among all patients, which researchers described as excellent.

In the follow-up study, Stephens and colleagues evaluated a subset of 336 patients (median age, 31 years; range, 18-60; 56% men), including 331 with central review of PET2 (82% PET2-negative; 18% PET2-positive).

With median follow-up of 5.9 years (range, 0.2-8.3), researchers estimated 5-year PFS of 74% (95% CI, 69-79) for all patients, 76% (95% CI, 70-81) for PET2-negative patients and 66% (95% CI, 52-76) for PET2-positive patients.

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Estimated 5-year OS for all patients was 94% (95% CI, 91-96).

Researchers observed a higher rate of reported second cancers among patients treated with eBEACOPP (14%; n = 7) than among patients treated with ABVD (2%; n = 6; P = .001).

Patients treated on the S0816 trial continue to have high rates of long-term OS, researchers noted. They added, however, that almost 25% of PET2-negative patients experienced relapse, illustrating the limitations of frontline ABVD and underscoring the negative predictive value of PET2.

“In PET2-positive patients who received eBEACOPP, PFS was favorable, but was associated with a high rate of second malignancies compared with historical controls,” Stephens and colleagues wrote. “Our results emphasize the importance of long-term follow-up, and the need for more efficacious and less toxic therapeutic approaches for advanced-stage [patients with] Hodgkin lymphoma.” – by Jennifer Byrne

Disclosures: Stephens reports research funding from Acerta, Gilead and Karyopharm and honoraria from Genentech. Please see the study for all other authors’ relevant financial disclosures.