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Interim PET results guide ongoing therapy in Hodgkin lymphoma

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Findings with immediate clinical utility
Dr. Mitchell Smith is with the Cleveland Clinic.

This large randomized phase 3 RATHL trial has practice changing implications for advanced stage Hodgkin lymphoma. This trial had a simple straightforward design uniting two themes in Hodgkin research: (1) desire to minimizeor omit bleomycin due to its somewhat unpredictable pulmonary toxicity; and (2) utilizing early PET response- adapted strategies, though most such studies have focused on early stage patients. This trial demonstrates that patients with advanced stage Hodgkin lymphoma who achieve PET negativity after 2 cycles of ABVD, representing 84% of patients, do not need to be exposed to bleomycin during the last 4 cycles, reducing pulmonary toxicity. This has immediate clinical utility. Whether this can be extrapolated to early stage patients remains an interesting research question.


 

AT 13-ICML

References

Bleomycin can be eliminated after two cycles of the ABVD chemotherapeutic regimen based on a negative interim PET scan finding in patients with Hodgkin lymphoma, according to the 3-year findings of the RATHL study.

Being able to omit bleomycin after a negative interim PET scan was associated with a lower rate of pulmonary toxicity, but no loss in efficacy. For patients with positive interim PET scans, a more aggressive therapy was associated with good outcomes, suggesting that response-adapted therapy can yield good results, Dr. Peter Johnson said at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

In the large international RATHL study (Response-Adapted Therapy in Hodgkin Lymphoma study) 1,137 adults with newly diagnosed disease (41% stage II, 31% stage III, 28% stage IV) underwent PET-CT scans at baseline and after completing two cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). The patients’ PET images were centrally reviewed using a 5-point scale as either negative (1-3) or positive (4-5),

The majority of patients (84%) had negative scans after two cycles of the ABVD regimen and were randomized to receive four additional cycles either with or without bleomycin (ABVD or AVD). Consolidation radiotherapy was not advised for patients whose interim PET scans were negative, regardless of baseline bulk or residual masses, Dr. Johnson, of the Cancer Research UK Centre at University of Southampton, England, reported.

Patients with positive interim PET scans received escalated therapy with a BEACOPP (bleomycin, etoposide, doxorubicin [Adriamycin], cyclophosphamide, vincristine [Oncovin], procarbazine, prednisolone) regimen. They received either eBEACOPP and BEASCOPP-14.

At the 3-year follow-up, progression-free survival in the PET-negative group was 85% for both the ABVD- and AVD-treated patients. Similarly, overall survival was 97% for both groups.

Factors that predicted treatment failure after a negative interim PET scan were initial tumor stage and international prognostic score, but not bulk, B symptoms, or score of the interim PET scan.

ABVD was associated with more pulmonary toxicity than was AVD.

Of 174 patients who had a positive interim PET scan and received escalated therapy, 74% had a subsequent negative PET scan after treatment. Their 3-year, progression-free survival rate was 68%, and their overall survival was 86% with no difference in outcome between two variations of BEACOPP (eBEACOPP and BEASCOPP-14).

Of the 53 deaths in the study, 19 were caused by Hodgkin lymphoma. The overall 3-year progression-free survival is 83%, and overall survival is 95%.

The results of the RATHL study have important implications for therapy of Hodgkin lymphoma, Dr. Johnson stated. First, interim PET scans are highly predictive for response to ABVD, providing valuable prognostic information to support decisions related to escalation of therapy. Secondly, after two cycles of ABVD, “it is safe to omit bleomycin from subsequent cycles, without consolidation radiotherapy,” he reported.

Omitting bleomycin has the potential to reduce pulmonary toxicity from chemotherapy, especially dyspnea, thromboembolism, and neutropenic fever, Dr. Johnson added. In the RATHL study, rates of pulmonary toxicity were significantly higher in the group receiving bleomycin.

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