Risk-Adapted, Chemotherapy-Alone Treatment Strategy Effective for Early-Stage Hodgkin Lymphoma

Detection of disease on interim PET/CT scans after two cycles of chemotherapy is a powerful predictor of outcomes in patients with early-stage, non-bulky Hodgkin lymphoma (HL), according to a study published in Blood. Investigators also determined that incorporating imaging results into a risk-adapted treatment strategy could identify patients who would benefit from a short course of chemotherapy, without the need for radiation therapy.

“This study reports an important finding, since most relapses [of newly diagnosed, stage I and II HL] will likely occur within three years,” lead author David J. Straus, MD, of the Memorial Sloan Kettering Cancer Center, told ASH Clinical News. “Chemotherapy-only treatment that avoids the potential risks of late morbidity and mortality associated with radiation therapy techniques is a feasible option for these patients.”

The phase II CALGB 50604 trial enrolled 164 patients with previously untreated, non-bulky, stage I or II HL between May 2010 and February 2013. In the 149 patients included in the final analysis, median age was 31 years (range = 18-58 years) and most patients had stage IIA disease (n=92; 56%).

All patients received treatment with two cycles of ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine), at which point they underwent PET/CT scans.

If PET scans were negative (Deauville score 1-3), patients received an additional two cycles of ABVD for a total of four treatment cycles; if PET scans were positive (Deauville scores 4-5), patients received two cycles of escalated BEACOPP (doxorubicin, cyclophosphamide, etoposide, procarbazine, prednisone, bleomycin, vincristine) and involved-field radiation therapy.

On central review, 135 patients (91%) were interim PET-negative, and 14 (9%) were interim PET-positive.

After a median follow-up of 3.8 years (range = 0.1-5.7 years), the overall estimated rate of three-year progression-free survival (PFS; primary endpoint) was 89 percent. The rate of three-year PFS was significantly higher among the PET-negative patients (91% vs. 66%; p=0.01) and exceeded the 85-percent threshold set as a criterion for “a positive result” in this trial. This translated to a hazard ratio for threeyear PFS of 3.84 (95% CI 1.50-9.84) for patients who had negative interim PET scans.

The complete response rate at the end of treatment was 97 percent for PET-negative patients and 85 percent for PET-positive patients.

The most common grade ≥3 adverse events (AEs) in patients with interim PET-negative scans who received four cycles of ABVD included neutropenia (n=92; 70%) and leukopenia (n=46; 35%). The most common grade ≥3 AEs for interim PET-positive patients were neutropenia (n=9; 69%), leukopenia (n=7; 54%), febrile neutropenia (n=7; 54%), and anemia (n=2; 15%).

Sixteen patients had relapsed disease: 13 PET-negative patients and three PET-positive patients. Eleven of the relapses were observed in the initial nodal sites of involvement, while three relapses were observed in new sites. This analysis did not report details regarding the subsequent treatment for relapses. “Although there may be a slightly higher relapse rate for patients treated with only chemotherapy as compared with chemotherapy and radiation therapy, the relapsed patients can be successfully salvaged, sometimes with radiation therapy only,” Dr. Straus said.

While the study met its primary endpoint of demonstrating high rates of three-year PFS in PET-negative patients receiving only chemotherapy, the researchers were not able to determine a PFS benefit with intensified BEACOPP plus radiation therapy in patients who were PET-positive after two cycles of ABVD. The estimated three-year PFS rate in this population was 54 percent, although “the numbers are probably too small to draw firm conclusions,” the authors noted. “While escalated BEACOPP may be a promising treatment option for PET-positive patients with advanced disease, it is less compelling for early-stage patients in view of the short- and anticipated long-term toxicities of this approach,” they added.

The non-randomized design and small population also were noted as potential limitations.

The authors reported no conflicts of interest.

Reference

Straus DJ, Jung S, Pitcher B, et al. CALGB 50604: risk-adapted treatment of non-bulky early stage Hodgkin lymphoma based on interim PET. Blood. 2018 July 26.

“This is the second large clinical trial to support de-escalation of therapy for patients with early-stage, non-bulky HL with a negative interim PET scan, particularly in terms of assessing safety and PFS. Given that most of the patients in the U.S. intergroup trial reported by Dr. Straus and colleagues are young, the avoidance of radiation has important long-term health implications. Either of the treatment paradigms mentioned here are very appropriate strategies to consider in patients with early-stage, non-bulky HL.”

Brad S. Kahl, MD
Washington University School of Medicine in St. Louis
St. Louis, Missouri

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